Entity Name Entity type Gene Symbol Sources(; separated) Level4 Level3 Level2 Model_Of_Inheritance Phenotypes Omim Orphanet HPO Publications Description Flagged GEL_Status UserRatings_Green_amber_red version ready Mode of pathogenicity EnsemblId(GRch37) EnsemblId(GRch38) HGNC Position Chromosome Position GRCh37 Start Position GRCh37 End Position GRCh38 Start Position GRCh38 End STR Repeated Sequence STR Normal Repeats STR Pathogenic Repeats Region Haploinsufficiency Score Region Triplosensitivity Score Region Required Overlap Percentage Region Variant Type Region Verbose Name AAAS gene AAAS Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Achalasia-addisonianism-alacrimia syndrome, OMIM:231550;Triple-A syndrome, MONDO:0009279 20931227;25529582 False 3 100;0;0 30.556 False ENSG00000094914 ENSG00000094914 HGNC:13666 AARS gene AARS Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental and epileptic encephalopathy 29, OMIM:616339;Developmental and epileptic encephalopathy, 29, MONDO:0014593 25817015 False 3 33;67;0 30.556 False ENSG00000090861 ENSG00000090861 HGNC:20 AARS gene AARS Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental and epileptic encephalopathy 29, OMIM:616339;Developmental and epileptic encephalopathy, 29, MONDO:0014593 28493438;25817015 False 3 100;0;0 30.556 False ENSG00000090861 ENSG00000090861 HGNC:20 AARS2 gene AARS2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 8, 614096;infantile mitochondrial cardiomyopathy PMID: 21549344;25058219 False 3 100;0;0 30.556 True ENSG00000124608 ENSG00000124608 HGNC:21022 AARS2 gene AARS2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukoencephalopathy with ovarian failure;General Leukodystrophy & Mitochondrial Leukoencephalopathy 24808023;27251004;25655951;25705216 False 3 0;0;0 30.556 False ENSG00000124608 ENSG00000124608 HGNC:21022 AARS2 gene AARS2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only);Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 8, 614096;infantile mitochondrial cardiomyopathy 27604308 False 3 100;0;0 30.556 False ENSG00000124608 ENSG00000124608 HGNC:21022 AASS gene AASS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperlysinemia, OMIM:238700;Hyperlysinemia (disease), MONDO:0009388 23890588;10775527;27604308;23570448 False 3 0;100;0 30.556 False ENSG00000008311 ENSG00000008311 HGNC:17366 AASS gene AASS Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperlysinemia, OMIM:238700;Hyperlysinemia (disease), MONDO:0009388 934735;10775527 False 3 33;67;0 30.556 False ENSG00000008311 ENSG00000008311 HGNC:17366 ABAT gene ABAT London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 613163;GABA transaminase deficiency (Disorders of neurotransmitter metabolism, gamma-aminobutyrate);mtDNA depletion syndrome 27604308 False 3 75;0;25 30.556 False ENSG00000183044 ENSG00000183044 HGNC:23 ABAT gene ABAT Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal GABA-transaminase deficiency, 613163;developmental delay 27596361;28411234;29517884;29631977;27903293 False 3 80;0;20 30.556 False ENSG00000183044 ENSG00000183044 HGNC:23 ABAT gene ABAT Victorian Clinical Genetics Services;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal mtDNA depletion syndrome;613163 Besse et al., 2015, Cell Metab., 21(3), 417-427 PMID: 25738457 False 3 67;0;33 30.556 True ENSG00000183044 ENSG00000183044 HGNC:23 ABCA1 gene ABCA1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Tangier disease (Disorders of high density lipoprotein metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000165029 ENSG00000165029 HGNC:29 ABCA2 gene ABCA2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder with poor growth and with or without seizures or ataxia, OMIM:618808;Intellectual developmental disorder with poor growth and with or without seizures or ataxia, MONDO:0032930 30237576;29302074;31047799 False 3 100;0;0 30.556 False ENSG00000107331 ENSG00000107331 HGNC:32 ABCB11 gene ABCB11 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Progressive familial intrahepatic cholestasis type 2 (Disorders of bile acid metabolism and transport);Cholestasis, benign recurrent intrahepatic, 2 605479;Cholestasis, progressive familial intrahepatic 2 601847 27604308 False 3 100;0;0 30.556 False ENSG00000073734 ENSG00000073734 HGNC:42 ABCB4 gene ABCB4 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Gallbladder disease 1 600803 AD, AR;Cholestasis, progressive familial intrahepatic 3 602347 AR;Progressive familial intrahepatic cholestasis type 3 (Disorders of bile acid metabolism and transport);Cholestasis, intrahepatic, of pregnancy, 3 614972 AD, AR 27604308 False 3 100;0;0 30.556 False ENSG00000005471 ENSG00000005471 HGNC:45 ABCB7 gene ABCB7 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Anemia, sideroblastic, with ataxia OMIM:301310;X-linked sideroblastic anemia with ataxia MONDO:0010524 27604308 False 3 50;0;50 30.556 False ENSG00000131269 ENSG00000131269 HGNC:48 ABCB7 gene ABCB7 Victorian Clinical Genetics Services;Expert Review Green;Expert list;Expert Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Disorders of iron homeostasis;Anemia, sideroblastic, with ataxia;congenital cerebellar hypoplasia/atrophy (PMID: 26242992). PMID: 26242992;22398176;17192398 False 3 100;0;0 30.556 False ENSG00000131269 ENSG00000131269 HGNC:48 ABCC9 gene ABCC9 NHS GMS;Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability and myopathy syndrome, OMIM:619719;intellectual disability and myopathy syndrome, MONDO:0859224 25529582;24896178;31575858;38217872 False 3 67;0;33 30.556 False ENSG00000069431 ENSG00000069431 HGNC:60 ABCD1 gene ABCD1 Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Adrenoleukodystrophy, OMIM:300100;Adrenoleukodystrophy, adult, OMIM:300100 8040304;11810273;25655951 False 3 0;0;0 30.556 False ENSG00000101986 ENSG00000101986 HGNC:61 ABCD1 gene ABCD1 Victorian Clinical Genetics Services;Expert Review Green;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Adrenoleukodystrophy, OMIM:300100;Adrenoleukodystrophy, adult, OMIM:300100 False 3 100;0;0 30.556 False ENSG00000101986 ENSG00000101986 HGNC:61 ABCD1 gene ABCD1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Adrenoleukodystrophy, OMIM:300100;Adrenoleukodystrophy, adult, OMIM:300100 27604308 False 3 0;100;0 30.556 False ENSG00000101986 ENSG00000101986 HGNC:61 ABCD4 gene ABCD4 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Methylmalonic aciduria and homocystinuria, cblJ type, 614857;METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, CBLJ TYPE; MAHCJ False 3 100;0;0 30.556 False ENSG00000119688 ENSG00000119688 HGNC:68 ABCD4 gene ABCD4 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Methylmalonic aciduria and homocystinuria, cblJ type 27604308;23141461;25234635 False 3 0;0;0 30.556 False ENSG00000119688 ENSG00000119688 HGNC:68 ABCG5 gene ABCG5 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sitosterolaemia (Inherited hypercholesterolaemias);Familial hypercholesterolaemia 27604308 False 3 100;0;0 30.556 False ENSG00000138075 ENSG00000138075 HGNC:13886 ABCG8 gene ABCG8 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sitosterolaemia (Inherited hypercholesterolaemias);Familial hypercholesterolaemia 27604308 False 3 100;0;0 30.556 False ENSG00000143921 ENSG00000143921 HGNC:13887 ABHD12 gene ABHD12 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hereditary ataxia;Posterior segment abnormalities;Congenital hearing impairment (profound/severe);PHARC syndrome (Disorders of complex lipid synthesis) 27604308 False 3 100;0;0 30.556 False ENSG00000100997 ENSG00000100997 HGNC:15868 ABHD16A gene ABHD16A Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia;Intellectual disability 34587489 False 3 100;0;0 30.556 False ENSG00000204427 ENSG00000204427 HGNC:13921 ABHD16A gene ABHD16A Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia;Intellectual disability 34587489 False 3 100;0;0 30.556 False ENSG00000204427 ENSG00000204427 HGNC:13921 ABHD5 gene ABHD5 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Chanarin-Dorfman syndrome 275630;Neutral lipid storage disease (Disorders of lipolysis) 27604308 False 3 100;0;0 30.556 False ENSG00000011198 ENSG00000011198 HGNC:21396 ABHD5 gene ABHD5 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Chanarin-Dorfman syndrome, OMIM:275630 False 3 33;0;67 30.556 False ENSG00000011198 ENSG00000011198 HGNC:21396 ACACA gene ACACA NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Acetyl-CoA carboxylase deficiency, OMIM: 613933 6114432;34552920;36709796 False 3 50;50;0 30.556 False ENSG00000132142 ENSG00000278540 HGNC:84 ACACA gene ACACA NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Acetyl-CoA carboxylase deficiency, OMIM: 613933 6114432;34552920;36709796 False 3 50;50;0 30.556 False ENSG00000132142 ENSG00000278540 HGNC:84 ACAD8 gene ACAD8 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isobutyric aciduria (Organic acidurias) 27604308 False 3 100;0;0 30.556 False ENSG00000151498 ENSG00000151498 HGNC:87 ACAD9 gene ACAD9 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency due to ACAD9 deficiency;ACAD9 deficiency, 611126;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors);Isolated complex I deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000177646 ENSG00000177646 HGNC:21497 ACAD9 gene ACAD9 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ACAD9 deficiency, 611126;ACYL-COA DEHYDROGENASE FAMILY MEMBER TYPE 9 DEFICIENCY False 3 100;0;0 30.556 False ENSG00000177646 ENSG00000177646 HGNC:21497 ACAD9 gene ACAD9 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;ACAD9 deficiency, 611126;Mitochondrial complex I deficiency due to ACAD9 deficiency PMID:17564966;21057504 False 3 100;0;0 30.556 True ENSG00000177646 ENSG00000177646 HGNC:21497 ACADM gene ACADM NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Acyl-CoA dehydrogenase, medium chain, deficiency of;Medium - chain acyl CoA dehydrogenase deficiency (Disorders of mitochondrial fatty acid oxidation) 27604308;24816252 False 3 33;33;33 30.556 False ENSG00000117054 ENSG00000117054 HGNC:89 ACADM gene ACADM Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MEDIUM CHAIN ACYL-COENZYME A DEHYDROGENASE DEFICIENCY 7603790;1684086;1972503;7929823;6434827;11409868;9158144;11349232 False 3 33;67;0 30.556 False ENSG00000117054 ENSG00000117054 HGNC:89 ACADS gene ACADS NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Acyl-CoA dehydrogenase, short-chain, deficiency of 27604308;24816252 False 3 0;0;100 30.556 False ENSG00000122971 ENSG00000122971 HGNC:90 ACADS gene ACADS Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Acyl-CoA dehydrogenase, short-chain, deficiency of 201470 False 3 100;0;0 30.556 False Other - please provide details in the comments ENSG00000122971 ENSG00000122971 HGNC:90 ACADSB gene ACADSB NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 2-methylbutyrylglycinuria 610006;2-Methylbutyric aciduria (Organic acidurias) 27604308 False 3 0;0;100 30.556 False ENSG00000196177 ENSG00000196177 HGNC:91 ACADVL gene ACADVL NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal VLCAD deficiency;Very long - chain acyl CoA dehydrogenase deficiency (Disorders of mitochondrial fatty acid oxidation) 27604308 False 3 50;0;50 30.556 False ENSG00000072778 ENSG00000072778 HGNC:92 ACAT1 gene ACAT1 NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cytosolic acetoacetyl-CoA thiolase deficiency (Disorders of ketone body metabolism);Fasting intolerance with acidosis, ? residual neurological problems;3-Oxothiolase deficiency (Organic acidurias) 27604308 False 3 0;0;100 30.556 False ENSG00000075239 ENSG00000075239 HGNC:93 ACBD5 gene ACBD5 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Retinal dystrophy with leukodystrophy, OMIM:618863 23105016;27899449;27799409;33427402 False 3 100;0;0 30.556 False ENSG00000107897 ENSG00000107897 HGNC:23338 ACBD6 gene ACBD6 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785 21937992;32108178;36457943;37951597 False 3 33;33;33 30.556 False ENSG00000230124 ENSG00000230124 HGNC:23339 ACER3 gene ACER3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, progressive, early childhood-onset, OMIM:617762 26792856;32816236;34281620 False 3 67;33;0 30.556 False ENSG00000078124 ENSG00000078124 HGNC:16066 ACER3 gene ACER3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, progressive, early childhood-onset, OMIM:617762 26792856;32816236;34281620 False 3 50;50;0 30.556 False ENSG00000078124 ENSG00000078124 HGNC:16066 ACO2 gene ACO2 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Infantile cerebellar-retinal degeneration, 614559 34056600 False 3 100;0;0 30.556 True ENSG00000100412 ENSG00000100412 HGNC:118 ACO2 gene ACO2 NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Infantile cerebellar-retinal degeneration, 614559 34056600 False 3 100;0;0 30.556 False ENSG00000100412 ENSG00000100412 HGNC:118 ACO2 gene ACO2 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Infantile cerebellar-retinal degeneration, OMIM:614559;Infantile cerebellar-retinal degeneration, MONDO:0013802 22405087;25351951;34056600 False 3 0;100;0 30.556 False ENSG00000100412 ENSG00000100412 HGNC:118 ACOX1 gene ACOX1 NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Peroxisomal acyl-CoA oxidase deficiency, OMIM:264470;Mitchell syndrome, OMIM:618960;General Leukodystrophy & Mitochondrial Leukoencephalopathy 17458872;25655951;11815777;32169171 False 3 100;0;0 30.556 False ENSG00000161533 ENSG00000161533 HGNC:119 ACOX1 gene ACOX1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisomal acyl-CoA oxidase deficiency, OMIM:264470;Mitchell syndrome, OMIM:618960 False 3 100;0;0 30.556 False ENSG00000161533 ENSG00000161533 HGNC:119 ACOX1 gene ACOX1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisomal acyl-CoA oxidase deficiency, OMIM:264470 27604308 False 3 0;0;0 30.556 False ENSG00000161533 ENSG00000161533 HGNC:119 ACOX2 gene ACOX2 Expert Review Green;NHS GMS;ClinGen;Other Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Bile acid synthesis defect, congenital, 6, OMIM:617308 27647924;27884763;29287774;33340570;35395098 False 3 100;0;0 30.556 False ENSG00000168306 ENSG00000168306 HGNC:120 ACP5 gene ACP5 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spondyloenchondrodysplasia, short stature, SLE, intracranial calcification, spasticity, chilblains, autoimmune haemolytic anaemia;Spondyloenchondrodysplasia with immune dysregulation 21217752;21217755;26951490 False 3 0;0;0 30.556 False ENSG00000102575 ENSG00000102575 HGNC:124 ACSF3 gene ACSF3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined malonic and methylmalonic aciduria, OMIM:614265 21785126;26915364;30740739;26827111;27604308;21841779 False 3 0;100;0 30.556 False ENSG00000176715 ENSG00000176715 HGNC:27288 ACSL4 gene ACSL4 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked 63, OMIM:300387;Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome, MONDO:0010263 12525535;11889465 False 3 100;0;0 30.556 False ENSG00000068366 ENSG00000068366 HGNC:3571 ACTB gene ACTB Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Dystonia, juvenile-onset, 607371Baraitser-Winter syndrome 1, 243310;BARAITSER-WINTER SYNDROME 22366783;25529582;24896178 False 3 100;0;0 30.556 False ENSG00000075624 ENSG00000075624 HGNC:132 ACTG1 gene ACTG1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Deafness, autosomal dominant 20/26, 604717Baraitser-Winter syndrome 2, 614583;BARAITSER-WINTER SYNDROME False 3 100;0;0 30.556 False ENSG00000184009 ENSG00000184009 HGNC:144 ACTL6A gene ACTL6A Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown developmental delay; intellectual disability 28649782 False 3 33;0;67 30.556 False ENSG00000136518 ENSG00000136518 HGNC:24124 ACTL6B gene ACTL6B Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Developmental and epileptic encephalopathy 76, OMIM:618468;Intellectual developmental disorder with severe speech and ambulation defects, OMIM:618470 26350204;31031012;30656450;26539891;27171548;30237576 False 3 25;0;75 30.556 False ENSG00000077080 ENSG00000077080 HGNC:160 ACY1 gene ACY1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;Aminoacylase 1 deficiency (Organic acidurias) 27604308 False 3 100;0;0 30.556 False ENSG00000243989 ENSG00000243989 HGNC:177 ACY1 gene ACY1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Aminoacylase 1 deficiency, 609924;AMINOACYLASE-1 DEFICIENCY False 3 100;0;0 30.556 False ENSG00000243989 ENSG00000243989 HGNC:177 ADA gene ADA Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Severe combined immunodeficiency due to ADA deficiency, OMIM:102700;Adenosine deaminase deficiency, partial, OMIM:102700 27604308 False 3 100;0;0 30.556 False ENSG00000196839 ENSG00000196839 HGNC:186 ADAM22 gene ADAM22 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Epileptic encephalopathy, early infantile, 61 OMIM:617933;developmental and epileptic encephalopathy, 61 MONDO:0033370 27066583;30237576 False 3 100;0;0 30.556 False ENSG00000008277 ENSG00000008277 HGNC:201 ADAR gene ADAR London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Aicardi-Goutieres syndrome 6, OMIM:615010;Dyschromatosis symmetrica hereditaria, OMIM:127400 27604308;12916015;23001123 False 3 0;0;0 30.556 False ENSG00000160710 ENSG00000160710 HGNC:225 ADAR gene ADAR Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Aicardi-Goutieres syndrome 6, OMIM:615010;Dyschromatosis symmetrica hereditaria, OMIM:127400 Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_584 False 3 0;0;0 30.556 False ENSG00000160710 ENSG00000160710 HGNC:225 ADAR gene ADAR Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Aicardi-Goutieres syndrome 6, OMIM:615010;Dyschromatosis symmetrica hereditaria, OMIM:127400 False 3 100;0;0 30.556 False ENSG00000160710 ENSG00000160710 HGNC:225 ADARB1 gene ADARB1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with hypotonia, microcephaly, and seizures, 618862 32220291;32719099 False 3 100;0;0 30.556 False ENSG00000197381 ENSG00000197381 HGNC:226 ADAT3 gene ADAT3 Expert Review Green;Literature;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with brain abnormalities, poor growth, and dysmorphic facies, OMIM:615286 23620220;26842963;30296593;29796286 False 3 100;0;0 30.556 False ENSG00000213638 ENSG00000213638 HGNC:25151 ADD1 gene ADD1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Global developmental delay;Intellectual disability;Seizures;Ventriculomegaly;Abnormality of the corpus callosum 34906466 False 3 50;50;0 30.556 False ENSG00000087274 ENSG00000087274 HGNC:243 ADD3 gene ADD3 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cerebral palsy, spastic quadriplegic, 3, MIM#617008 29768408;23836506 False 3 100;0;0 30.556 False ENSG00000148700 ENSG00000148700 HGNC:245 ADGRG1 gene ADGRG1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Polymicrogyria, bilateral frontoparietal, 606854 False 3 100;0;0 30.556 False ENSG00000205336 ENSG00000205336 HGNC:4512 ADGRL1 gene ADGRL1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental delay, behavioral abnormalities, and neuropsychiatric disorders, OMIM:620065 30504930;35907405 False 3 100;0;0 30.556 False ENSG00000072071 ENSG00000072071 HGNC:20973 ADK gene ADK Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypermethioninemia due to adenosine kinase deficiency 614300 False 3 33;0;67 30.556 False ENSG00000156110 ENSG00000156110 HGNC:257 ADNP gene ADNP Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted MENTAL RETARDATION, AUTOSOMAL DOMINANT, 28; MRD28 24531329 False 3 100;0;0 30.556 False ENSG00000101126 ENSG00000101126 HGNC:15766 ADSL gene ADSL Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ade(-)I bifunctional Adenylosuccinase deficiency, 103050;ADENYLOSUCCINASE DEFICIENCY (ADSL DEFICIENCY) False 3 100;0;0 30.556 False ENSG00000239900 ENSG00000239900 HGNC:291 ADSL gene ADSL Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;Epileptic encephalopathy;Adenylosuccinate lyase deficiency (Disorders of purine metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000239900 ENSG00000239900 HGNC:291 AFF2 gene AFF2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;UKGTN;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Intellectual developmental disorder, X-linked 109, OMIM:309548;FRAXE intellectual disability, MONDO:0010659 21739600;22065534;25529582;24896178;8334699;8023854;21739600;9299237;11171404;11923441;19136466;2356291 False 3 100;0;0 30.556 False Other - please provide details in the comments ENSG00000155966 ENSG00000155966 HGNC:3776 AFF3 gene AFF3 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown KINSSHIP syndrome, OMIM:619297 18616733;21677750;25660031;31388108;33961779 False 3 67;33;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000144218 ENSG00000144218 HGNC:6473 AFF4 gene AFF4 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted CORNELIA DE LANGE-LIKE SYNDROME 25730767 False 3 50;50;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000072364 ENSG00000072364 HGNC:17869 AFG3L2 gene AFG3L2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Optic atrophy 12, OMIM:618977;Spinocerebellar ataxia 28, OMIM:610246;Spastic ataxia 5, autosomal recessive, OMIM:614487 27604308 False 3 100;0;0 30.556 False ENSG00000141385 ENSG00000141385 HGNC:315 AFG3L2 gene AFG3L2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Optic atrophy 12, OMIM:618977;Spinocerebellar ataxia 28, OMIM:610246;Spastic ataxia 5, autosomal recessive, OMIM:614487 False 3 100;0;0 30.556 True ENSG00000141385 ENSG00000141385 HGNC:315 AGA gene AGA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Aspartylglucosaminuria 27604308 False 3 0;0;0 30.556 False ENSG00000038002 ENSG00000038002 HGNC:318 AGA gene AGA Expert Review Green;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Aspartylglucosaminuria, 208400;ASPARTYLGLUCOSAMINURIA (AGU) False 3 100;0;0 30.556 False ENSG00000038002 ENSG00000038002 HGNC:318 AGK gene AGK London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of mitochondrial membrane lipids (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Mitochondrial DNA depletion syndrome 10;Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Acylglycerol kinase deficiency (Senger syndrome) (Disorders of complex lipid synthesis);Sengers syndrome, 212350;Sengers syndrome 212350;Disorders of mitochondrial lipid metabolism;Cataract 38, autosomal recessive, 614691 27604308 False 3 100;0;0 30.556 False ENSG00000006530 ENSG00000006530 HGNC:21869 AGK gene AGK Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sengers syndrome, 212350;Mitochondrial DNA depletion syndrome 10;Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Disorders of mitochondrial lipid metabolism;Cataract 38, autosomal recessive, 614691 False 3 100;0;0 30.556 True ENSG00000006530 ENSG00000006530 HGNC:21869 AGL gene AGL London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycogen storage disease type III, Cori (Glycogen storage disorders);Glycogen storage disease IIIb, 232400;Glycogen Storage Disorders- Liver;Glycogen Storage Disease;myopathy, cardiomyopathy and neuropathy possible but mile hepatomegaly and fasting intolerance;Glycogen Storage Disease Type III;Glycogen Storage Disorders- Muscle;Glycogen storage disease IIIa, 232400 27604308 False 3 100;0;0 30.556 False ENSG00000162688 ENSG00000162688 HGNC:321 AGO1 gene AGO1 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures, OMIM:620292 26350204;30213762;22495306;23020937;25363768;25356899;27620904;29346770;28135719;34930816 False 3 40;0;60 30.556 False ENSG00000092847 ENSG00000092847 HGNC:3262 AGO2 gene AGO2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual disability;regression;seizures 33199684 False 3 50;50;0 30.556 False ENSG00000123908 ENSG00000123908 HGNC:3263 AGPS gene AGPS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Rhizomelic chondrodysplasia punctata, type 3 600121;Rhizomelic chondrodysplasia punctata type 3 (Peroxisomal disorders) 27604308 False 3 0;0;0 30.556 False ENSG00000018510 ENSG00000018510 HGNC:327 AGTPBP1 gene AGTPBP1 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodegeneration, childhood-onset, with cerebellar atrophy, OMIM:618276 30420557 False 3 100;0;0 30.556 False ENSG00000135049 ENSG00000135049 HGNC:17258 AGXT gene AGXT London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Primary hyperoxaluria type I (Other peroxisomal disorders);Primary hyperoxaluria type I (Disorders of glyoxylate metabolism);Hyperoxaluria, primary, type 1 27604308 False 3 0;0;0 30.556 False ENSG00000172482 ENSG00000172482 HGNC:341 AHCY gene AHCY Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase, 613752;Disorders of the metabolism of sulphur amino acids 15024124;16435181;16736098;20852937;22959829;26095522;26527160;28779239;30121674;31957987 False 3 50;0;50 30.556 False ENSG00000101444 ENSG00000101444 HGNC:343 AHCY gene AHCY Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase, 613752 15024124;16435181;16736098;20852937;22959829;26095522;26527160;28779239;30121674;31957987 False 3 25;0;75 30.556 False ENSG00000101444 ENSG00000101444 HGNC:343 AHDC1 gene AHDC1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted XIA-GIBBS SYNDROME 24791903 False 3 33;67;0 30.556 False ENSG00000126705 ENSG00000126705 HGNC:25230 AHI1 gene AHI1 Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Joubert syndrome 3 608629 15322546; 16453322 False 3 50;0;50 30.556 False ENSG00000135541 ENSG00000135541 HGNC:21575 AIFM1 gene AIFM1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Disorders of mitochondrial apoptosis;Cowchock syndrome, 310490;Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Combined oxidative phosphorylation deficiency 6, 300816 27604308 False 3 100;0;0 30.556 False ENSG00000156709 ENSG00000156709 HGNC:8768 AIFM1 gene AIFM1 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy, OMIM:300232 28842795;27102849;33439541 False 3 100;0;0 30.556 False ENSG00000156709 ENSG00000156709 HGNC:8768 AIFM1 gene AIFM1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Cowchock syndrome, OMIM:310490;Combined oxidative phosphorylation deficiency 6, OMIM:300816;Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy, OMIM:300232 False 3 100;0;0 30.556 False ENSG00000156709 ENSG00000156709 HGNC:8768 AIFM1 gene AIFM1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Disorders of mitochondrial apoptosis;Combined oxidative phosphorylation deficiency 6, 300816;Cowchock syndrome, 310490 PMID: 20362274 (two related males);PMID: 23217327 False 3 100;0;0 30.556 True ENSG00000156709 ENSG00000156709 HGNC:8768 AIMP1 gene AIMP1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 3, OMIM:260600 False 3 100;0;0 30.556 False ENSG00000164022 ENSG00000164022 HGNC:10648 AIMP1 gene AIMP1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 3, OMIM:260600 False 3 0;0;0 30.556 False ENSG00000164022 ENSG00000164022 HGNC:10648 AKR1D1 gene AKR1D1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?4-3-oxysterol 5?-reductase deficiency (Disorders of bile acid biosynthesis);Bile acid synthesis defect, congenital, 2 235555 27604308;24816252 False 3 100;0;0 30.556 False ENSG00000122787 ENSG00000122787 HGNC:388 AKT3 gene AKT3 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, OMIM:615937 22729224;22500628 False 3 100;0;0 30.556 False ENSG00000117020 ENSG00000117020 HGNC:393 ALAD gene ALAD London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal {Lead poisoning, susceptibility to} 612740;Acute hepatic porphyria (Acute neuropathic porphyrias);Porphyria, acute hepatic 612740 27604308 False 3 100;0;0 30.556 False ENSG00000148218 ENSG00000148218 HGNC:395 ALAS2 gene ALAS2 Expert Review Green;Expert list;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Anemia, sideroblastic, 1, OMIM:300751;Protoporphyria, erythropoietic, X-linked, OMIM:300752 27604308 False 3 100;0;0 30.556 False ENSG00000158578 ENSG00000158578 HGNC:397 ALDH18A1 gene ALDH18A1 Expert list;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Cutis laxa, autosomal dominant 3 OMIM:616603;cutis laxa, autosomal dominant 3 MONDO:0014706;Cutis laxa, autosomal recessive, type IIIA OMIM:219150;ALDH18A1-related de Barsy syndrome MONDO:0009053;Spastic paraplegia 9A, autosomal dominant OMIM:601162;hereditary spastic paraplegia 9A MONDO:0011006;Spastic paraplegia 9B, autosomal recessive OMIM:616586;autosomal recessive complex spastic paraplegia type 9B MONDO:0014702 27604308;24816252;29903433;11092761;22170564;26320891 False 3 100;0;0 30.556 False ENSG00000059573 ENSG00000059573 HGNC:9722 ALDH18A1 gene ALDH18A1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Cutis laxa, autosomal recessive, type IIIA, 219150;SPASTIC PARAPLEGIA 9, AUTOSOMAL DOMINANT; SPG9 False 3 100;0;0 30.556 False ENSG00000059573 ENSG00000059573 HGNC:9722 ALDH3A2 gene ALDH3A2 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sjogren-Larsson syndrome, OMIM:270200 False 3 100;0;0 30.556 False ENSG00000072210 ENSG00000072210 HGNC:403 ALDH3A2 gene ALDH3A2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sjogren-Larsson syndrome, OMIM:270200;General Leukodystrophy & Mitochondrial Leukoencephalopathy 25655951 False 3 0;0;0 30.556 False ENSG00000072210 ENSG00000072210 HGNC:403 ALDH3A2 gene ALDH3A2 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sjogren-Larsson syndrome, OMIM:270200 27604308 False 3 100;0;0 30.556 False ENSG00000072210 ENSG00000072210 HGNC:403 ALDH4A1 gene ALDH4A1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperprolinemia, type II, 239510;HYPERPROLINEMIA TYPE 2 (HP-2) False 3 100;0;0 30.556 False ENSG00000159423 ENSG00000159423 HGNC:406 ALDH4A1 gene ALDH4A1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;Hyperprolinaemia type II (Disorders of ornithine or proline metabolism);Hyperprolinemia, type II 27604308 False 3 0;0;0 30.556 False ENSG00000159423 ENSG00000159423 HGNC:406 ALDH5A1 gene ALDH5A1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Succinic semialdehyde dehydrogenase deficiency OMIM:271980;succinic semialdehyde dehydrogenase deficiency MONDO:0010083 9683595;14635103;32402538;16542398 False 3 100;0;0 30.556 False ENSG00000112294 ENSG00000112294 HGNC:408 ALDH5A1 gene ALDH5A1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Succinic semialdehyde dehydrogenase deficiency OMIM:271980;succinic semialdehyde dehydrogenase deficiency MONDO:0010083 27604308;9683595;14635103;32402538 False 3 0;0;0 30.556 False ENSG00000112294 ENSG00000112294 HGNC:408 ALDH6A1 gene ALDH6A1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Methylmalonate semialdehyde dehydrogenase deficiency 614105;3-Hydroxyisobutyric aciduria (Organic acidurias);Methylmalonate semialdehyde dehydrogenase deficiency (Organic acidurias) 27604308 False 3 100;0;0 30.556 False ENSG00000119711 ENSG00000119711 HGNC:7179 ALDH7A1 gene ALDH7A1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal PYRIDOXINE-DEPENDENT EPILEPSY 17068770;16491085;17721876 False 3 33;67;0 30.556 False ENSG00000164904 ENSG00000164904 HGNC:877 ALDH7A1 gene ALDH7A1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epilepsy, pyridoxine-dependent 27604308 False 3 0;0;0 30.556 False ENSG00000164904 ENSG00000164904 HGNC:877 ALDOA gene ALDOA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycogen Storage Disease;Aldolase A deficiency (Glycogen storage disorders);Glycogen storage disease XII, 611881 27604308 False 3 100;0;0 30.556 False ENSG00000149925 ENSG00000149925 HGNC:414 ALDOB gene ALDOB London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal hereditary fructose intolerance;Hereditary fructose intolerance (Disorders of fructose metabolism);acidosis with ketototic hypoglycaemia often hepatomegaly in acute presentation 27604308 False 3 0;0;0 30.556 False ENSG00000136872 ENSG00000136872 HGNC:417 ALG1 gene ALG1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Ik, 608540;ALG1-CDG (CDG-IK) False 3 100;0;0 30.556 False ENSG00000033011 ENSG00000033011 HGNC:18294 ALG1 gene ALG1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mannosyltransferase 1 deficiency (Disorders of protein N-glycosylation);Congenital disorder of glycosylation, type Ik 608540 22966035;14973782;26931382 False 3 0;0;0 30.556 False ENSG00000033011 ENSG00000033011 HGNC:18294 ALG11 gene ALG11 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Ip 613661;ALG11-CDG (CDG-IP) 27604308;22213132;20080937 False 3 0;100;0 30.556 False ENSG00000253710 ENSG00000253710 HGNC:32456 ALG11 gene ALG11 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ALG11-CDG (Disorders of protein N-glycosylation);Congenital disorder of glycosylation, type Ip 613661 27604308 False 3 0;0;0 30.556 False ENSG00000253710 ENSG00000253710 HGNC:32456 ALG12 gene ALG12 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal CONGENITAL DISORDER OF GLYCOSYLATION TYPE 1G (CDG1G) 12093361;11983712;12217961 False 3 100;0;0 30.556 False ENSG00000182858 ENSG00000182858 HGNC:19358 ALG12 gene ALG12 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Ig 607143;Mannosyltransferase 8 deficiency (Disorders of protein N-glycosylation) 27604308;17506107;11983712 False 3 0;0;0 30.556 False ENSG00000182858 ENSG00000182858 HGNC:19358 ALG13 gene ALG13 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) EPILEPTIC ENCEPHALOPATHIES. 22492991 False 3 100;0;0 30.556 False ENSG00000101901 ENSG00000101901 HGNC:30881 ALG14 gene ALG14 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Myasthenic syndrome, congenital, 15, without tubular aggregates 616227;Congenital myasthenic sydrome (Disorders of protein N-glycosylation) 27604308;28733338;23404334;30221345 False 3 100;0;0 30.556 False ENSG00000172339 ENSG00000172339 HGNC:28287 ALG3 gene ALG3 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Id, 601110;ALG3-CDG (CDG-ID) 0 False 3 100;0;0 30.556 False ENSG00000214160 ENSG00000214160 HGNC:23056 ALG3 gene ALG3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mannosyltransferase 6 deficiency ALG3-CDG (Disorders of protein N-glycosylation);Congenital disorder of glycosylation, type Id 601110;Mannosyltransferase 6 deficiency (Disorders of protein N-glycosylation);ALG3-CDG (Disorders of protein N-glycosylation) 15108280;19862844 False 3 0;0;0 30.556 False ENSG00000214160 ENSG00000214160 HGNC:23056 ALG6 gene ALG6 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Ic 603147;Glucosyltransferase 1 deficiency (Disorders of protein N-glycosylation) 27604308 False 3 0;0;0 30.556 False ENSG00000088035 ENSG00000088035 HGNC:23157 ALG6 gene ALG6 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Ic, 603147;ALG6-CDG (CDG-IC) 0 False 3 100;0;0 30.556 False ENSG00000088035 ENSG00000088035 HGNC:23157 ALG8 gene ALG8 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Ih, 608104;ALG8-CDG (CDG-IH) 26066342,23430830,19688606;25529582 False 3 100;0;0 30.556 False ENSG00000159063 ENSG00000159063 HGNC:23161 ALG8 gene ALG8 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glucosyltransferase 2 deficiency (Disorders of protein N-glycosylation);Congenital disorder of glycosylation, type Ih 608104 27604308 False 3 0;0;0 30.556 False ENSG00000159063 ENSG00000159063 HGNC:23161 ALG9 gene ALG9 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mannosyltransferase 7-9 deficiency (Disorders of protein N-glycosylation);ALG9-CDG (Disorders of protein N-glycosylation);Congenital disorder of glycosylation, type Il 608776 27604308 False 3 0;0;0 30.556 False ENSG00000086848 ENSG00000086848 HGNC:15672 ALG9 gene ALG9 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental delay;Congenital disorder of glycosylation, type Il 608776;Gillessen-Kaesbach-Nishimura syndrome 263210 15945070;15148656;28932688;26453364 False 3 25;50;25 30.556 False ENSG00000086848 ENSG00000086848 HGNC:15672 ALKBH8 gene ALKBH8 Expert Review Green;NHS GMS;Expert Review;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder, autosomal recessive 71, OMIM:618504 31130284;31079898;33544954;34757492;35571055 False 3 100;0;0 30.556 False ENSG00000137760 ENSG00000137760 HGNC:25189 ALMS1 gene ALMS1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ALSTROM SYNDROME, 203800 17594715;11941370;11941369;9063741;21877133;17850632 False 3 33;67;0 30.556 False ENSG00000116127 ENSG00000116127 HGNC:428 ALPL gene ALPL Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Hypophosphatasia, adult, OMIM:146300;Hypophosphatasia, childhood, OMIM:241510;Hypophosphatasia, infantile, OMIM:241500;Odontohypophosphatasia, OMIM:146300 27604308;11745997;1409720;17213282 False 3 0;0;0 30.556 False ENSG00000162551 ENSG00000162551 HGNC:438 AMACR gene AMACR London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Alpha-methylacyl-CoA racemase deficiency;Alpha-methylacyl-CoA racemase deficiency (Disorders of peroxisomal alpha-, beta and omega-oxidation) 27604308 False 3 0;0;0 30.556 False ENSG00000242110 ENSG00000242110 HGNC:451 AMER1 gene AMER1 Expert Review Green;Victorian Clinical Genetics Services;BRIDGE study SPEED NEURO Tier1 Gene;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Osteopathia striata with cranial sclerosis 300373 False 3 100;0;0 30.556 False ENSG00000184675 ENSG00000184675 HGNC:26837 AMN gene AMN London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intrinsic factor receptor deficiency due to AMN mutations (Disorders of cobalamin absorption, transport and metabolism);Proteinuric renal disease;Unexplained kidney failure in young people 27604308 False 3 0;0;0 30.556 False ENSG00000166126 ENSG00000166126 HGNC:14604 AMPD2 gene AMPD2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal PONTOCEREBELLAR HYPOPLASIA;Pontocerebellar hypoplasia, type 9, 615809 23911318 False 3 33;67;0 30.556 False ENSG00000116337 ENSG00000116337 HGNC:469 AMT gene AMT London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycine encephalopathy 27604308 False 3 0;0;0 30.556 False ENSG00000145020 ENSG00000145020 HGNC:473 AMT gene AMT Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycine encephalopathy, 605899;GLYCINE ENCEPHALOPATHY False 3 100;0;0 30.556 False ENSG00000145020 ENSG00000145020 HGNC:473 ANK2 gene ANK2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Complex neurodevelopmental disorder, MONDO:0100038 22542183;25363768;27479843;28554332;30564305;30755392;31981491;33004838;33057194 False 3 100;0;0 30.556 False ENSG00000145362 ENSG00000145362 HGNC:493 ANK3 gene ANK3 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Intellectual developmental disorder, autosomal recessive 37, OMIM:615493;intellectual disability-hypotonia-spasticity-sleep disorder syndrome, MONDO:0014210 23390136;28687526;34218362 False 3 67;0;33 30.556 False ENSG00000151150 ENSG00000151150 HGNC:494 ANKRD11 gene ANKRD11 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted KBG syndrome, 148050;KBG SYNDROME 15378538;21782149;15523620;25529582;24896178;25424714;28250421 False 3 100;0;0 30.556 False ENSG00000167522 ENSG00000167522 HGNC:21316 ANKRD17 gene ANKRD17 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual disability, speech delay, and dysmorphism 33909992 False 3 100;0;0 30.556 False ENSG00000132466 ENSG00000132466 HGNC:23575 ANO10 gene ANO10 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spinocerebellar ataxia, autosomal recessive 10, 613728 False 3 50;0;50 30.556 False ENSG00000160746 ENSG00000160746 HGNC:25519 ANO4 gene ANO4 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown sporadic encephalopathic and familial epilepsy 38744284 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000151572 ENSG00000151572 HGNC:23837 AP1G1 gene AP1G1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder (NDD);Intellectual Disability;Epilepsy 34102099 False 3 100;0;0 30.556 False ENSG00000166747 ENSG00000166747 HGNC:555 AP1S1 gene AP1S1 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MEDNIK syndrome, 609313;MEDNIK syndrome;mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis and keratoderma syndrome 23423674;26927810;19057675;24754424 False 3 100;0;0 30.556 False ENSG00000106367 ENSG00000106367 HGNC:559 AP1S2 gene AP1S2 Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Pettigrew syndrome, OMIM:304340;Calcifications in basal ganglia 10398241;17186471;17617514;22210230;23756445;30383884;30714330 False 3 0;0;0 30.556 False ENSG00000182287 ENSG00000182287 HGNC:560 AP1S2 gene AP1S2 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Pettigrew syndrome, OMIM:304340 10398241;12599187;17186471;17617514;18428203;19377476;22210230;23756445;25649377;30383884;30714330 False 3 100;0;0 30.556 False ENSG00000182287 ENSG00000182287 HGNC:560 AP2M1 gene AP2M1 Expert Review;Expert Review Green;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual developmental disorder 60 with seizures, 618587;Seizures;Ataxia;Generalized hypotonia;Intellectual disability;Global developmental delay;Autistic behavior 31104773 False 3 50;50;0 30.556 False ENSG00000161203 ENSG00000161203 HGNC:564 AP3B1 gene AP3B1 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hermansky-Pudlak syndrome 2 608233 16551969 False 3 33;0;67 30.556 False ENSG00000132842 ENSG00000132842 HGNC:566 AP3B2 gene AP3B2 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epileptic encephalopathy, early infantile, 48 617276 27889060 False 3 100;0;0 30.556 False ENSG00000103723 ENSG00000103723 HGNC:567 AP4B1 gene AP4B1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 47, autosomal recessive, OMIM:614066;Hereditary spastic paraplegia 47, MONDO:0013551 False 3 100;0;0 30.556 False ENSG00000134262 ENSG00000134262 HGNC:572 AP4B1 gene AP4B1 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 47, autosomal recessive, OMIM:614066;Hereditary spastic paraplegia 47, MONDO:0013551 22290197;24700674;29193663;29430868;30337681 False 3 100;0;0 30.556 False ENSG00000134262 ENSG00000134262 HGNC:572 AP4E1 gene AP4E1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 51, autosomal recessive, OMIM:613744;Hereditary spastic paraplegia 51, MONDO:0013401 False 3 100;0;0 30.556 False ENSG00000081014 ENSG00000081014 HGNC:573 AP4M1 gene AP4M1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 50, autosomal recessive, 612936;CEREBRAL PALSY SPASTIC QUADRIPLEGIC TYPE 3 (CPSQ3) False 3 100;0;0 30.556 False ENSG00000221838 ENSG00000221838 HGNC:574 AP4S1 gene AP4S1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 52, autosomal recessive, 614067;CEREBRAL PALSY SPASTIC QUADRIPLEGIC TYPE 6 False 3 100;0;0 30.556 False ENSG00000100478 ENSG00000100478 HGNC:575 APC2 gene APC2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cortical dysplasia, complex, with other brain malformations 10 OMIM:618677 31585108;25753423;19759310;22573669 False 3 100;0;0 30.556 False ENSG00000115266 ENSG00000115266 HGNC:24036 APOA1 gene APOA1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Amyloidosis, 3 or more types OMIM:105200;familial visceral amyloidosis MONDO:0007099;ApoA-I and apoC-III deficiency, combined OMIM:618463;Hypoalphalipoproteinemia, primary, 2, with or without corneal clouding OMIM:618463;hypoalphalipoproteinemia, primary, 2 MONDO:0032766 27604308;26515634;12050338;32022753 False 3 100;0;0 30.556 False ENSG00000118137 ENSG00000118137 HGNC:600 APOA5 gene APOA5 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Hyperchylomicronemia, late-onset OMIM:144650;hyperlipoproteinemia type V MONDO:0007762;{Hypertriglyceridemia, susceptibility to} OMIM:145750;hypertriglyceridemia, familial MONDO:0007788 27604308;27678447;16200213;12417525;23307945 False 3 100;0;0 30.556 False ENSG00000110243 ENSG00000110243 HGNC:17288 APOB gene APOB Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Hypercholesterolemia, familial, 2 OMIM:144010;hypercholesterolemia, autosomal dominant, type B MONDO:0007751;Hypobetalipoproteinemia OMIM:615558;familial hypobetalipoproteinemia 1 MONDO:0014252 27604308 False 3 100;0;0 30.556 False ENSG00000084674 ENSG00000084674 HGNC:603 APOC2 gene APOC2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperlipoproteinemia, type Ib 207750;Familial apolipoprotein C - II deficiency (Familial chylomicronaemia, Inherited hypercholesterolaemias) 27604308 False 3 100;0;0 30.556 False ENSG00000234906 ENSG00000234906 HGNC:609 APOE gene APOE London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Familial dysbetalipoproteinaemia (Inherited mixed hyperlipidaemias);Hyperlipoproteinemia, type III 617347;Sea-blue histiocyte disease 269600;Lipoprotein glomerulopathy 611771 27604308;24816252 False 3 100;0;0 30.556 False ENSG00000130203 ENSG00000130203 HGNC:613 APOPT1 gene APOPT1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 17, OMIM:619061;Isolated complex IV deficiency False 3 100;0;0 30.556 False ENSG00000256053 ENSG00000256053 HGNC:20492 APOPT1 gene APOPT1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 17, OMIM:619061 25175347 False 3 33;67;0 30.556 False ENSG00000256053 ENSG00000256053 HGNC:20492 APOPT1 gene APOPT1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 17, OMIM:619061;Isolated complex IV deficiency False 3 100;0;0 30.556 True ENSG00000256053 ENSG00000256053 HGNC:20492 APOPT1 gene APOPT1 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 17, OMIM:619061 25175347 False 3 100;0;0 30.556 False ENSG00000256053 ENSG00000256053 HGNC:20492 APRT gene APRT London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Adenine phosphoribosyltransferase deficiency 614723;Adenine phosphoribosyl transferase deficiency (Disorders of purine metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000198931 ENSG00000198931 HGNC:626 APTX gene APTX London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Secondary CoQ10 deficiency (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Ataxia with oculomotor apraxia 1;Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia, 208920;Disorders of ubiquinone metabolism and biosynthesis 27604308 False 3 50;0;50 30.556 False ENSG00000137074 ENSG00000137074 HGNC:15984 APTX gene APTX Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of ubiquinone metabolism and biosynthesis;Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia, 208920;Ataxia with oculomotor apraxia 1 False 3 50;0;50 30.556 True ENSG00000137074 ENSG00000137074 HGNC:15984 ARCN1 gene ARCN1 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay, 617164 27476655 False 3 100;0;0 30.556 False ENSG00000095139 ENSG00000095139 HGNC:649 ARF1 gene ARF1 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Periventricular nodular heterotopia 8, OMIM:618185 28868155;34353862;36345169 False 3 100;0;0 30.556 False ENSG00000143761 ENSG00000143761 HGNC:652 ARF3 gene ARF3 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Global developmental delay;Intellectual disability, MONDO:0001071;Seizures;Morphological abnormality of the central nervous system;microcephaly, MONDO:0001149 34346499;36369169 False 3 67;33;0 30.556 False ENSG00000134287 ENSG00000134287 HGNC:654 ARFGEF1 gene ARFGEF1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual disability, MONDO:0001071;Epilepsy, MONDO:0005027;Developmental delay, impaired speech, and behavioral abnormalities, with or without seizures, OMIM:619964 34113008 False 3 100;0;0 30.556 False ENSG00000066777 ENSG00000066777 HGNC:15772 ARFGEF2 gene ARFGEF2 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Periventricular heterotopia with microcephaly, 608097;PERIVENTRICULAR HETEROTOPIA WITH MICROCEPHALY False 3 100;0;0 30.556 False ENSG00000124198 ENSG00000124198 HGNC:15853 ARG1 gene ARG1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Argininemia, OMIM:207800 False 3 100;0;0 30.556 False ENSG00000118520 ENSG00000118520 HGNC:663 ARG1 gene ARG1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Argininaemia (Urea cycle disorders and inherited hyperammonaemias);Argininemia, OMIM:207800 27604308 False 3 0;0;0 30.556 False ENSG00000118520 ENSG00000118520 HGNC:663 ARHGEF9 gene ARHGEF9 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Developmental and epileptic encephalopathy 8, OMIM:300607 False 3 100;0;0 30.556 False ENSG00000131089 ENSG00000131089 HGNC:14561 ARID1A gene ARID1A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Mental retardation, autosomal dominant 14, 614607;COFFIN-SIRIS SYNDROME; CSS False 3 100;0;0 30.556 False ENSG00000117713 ENSG00000117713 HGNC:11110 ARID1B gene ARID1B Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Mental retardation, autosomal dominant 12, 614562;COFFIN SIRIS SYNDROME False 3 100;0;0 30.556 False ENSG00000049618 ENSG00000049618 HGNC:18040 ARID2 gene ARID2 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Coffin-Siris syndrome 6, 617808;ARID2-Coffin-Siris like disorder 28124119;26238514;33051312 False 3 50;0;50 30.556 False ENSG00000189079 ENSG00000189079 HGNC:18037 ARL13B gene ARL13B Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Joubert syndrome 8, 612291;Intellectual disability 18674751;25138100;29255182;16541367 False 3 50;0;50 30.556 False ENSG00000169379 ENSG00000169379 HGNC:25419 ARL6 gene ARL6 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Bardet-Biedl syndrome 3, 209900{Bardet-Biedl syndrome 1, modifier of}, 209900Retinitis pigmentosa 55, 613575;BARDET-BIEDL SYNDROME TYPE 3 (BBS3) False 3 100;0;0 30.556 False ENSG00000113966 ENSG00000113966 HGNC:13210 ARMC9 gene ARMC9 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Joubert syndrome; Intellectual Disability 28625504 False 3 100;0;0 30.556 False ENSG00000135931 ENSG00000135931 HGNC:20730 ARSA gene ARSA Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Metachromatic leukodystrophy, 250100;Arylsulfatase A Deficiency False 3 0;0;0 30.556 False ENSG00000100299 ENSG00000100299 HGNC:713 ARSA gene ARSA Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ARYLSULFATASE A DEFICIENCY 7981715;11456299;1676699;1353340;1684088;2574462;11061266;8104633;9600244;1673291;8101038;7902317;7909527;7815433;1670590;7906588;12788103;1678251;7858169;7833949;8101083;11941485;7866401 False 3 33;67;0 30.556 False ENSG00000100299 ENSG00000100299 HGNC:713 ARSA gene ARSA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Metachromatic leukodystrophy 27604308;24816252 False 3 0;0;0 30.556 False ENSG00000100299 ENSG00000100299 HGNC:713 ARSB gene ARSB London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MUCOPOLYSACCHARIDOSIS TYPE 6;Mucopolysaccharidosis, Type VI;Mucopolysaccharidosis type VI (Maroteaux-Lamy), 253200;Mucopolysaccharidosis Type VI;MPS VI, Maroteaux - Lamy disease (MPS IV, Morquio disease) 27604308 False 3 0;0;0 30.556 False ENSG00000113273 ENSG00000113273 HGNC:714 ARSB gene ARSB Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MUCOPOLYSACCHARIDOSIS TYPE 6 (MPS6) 1718978;8651289;1550123;8723688;1301949;17643332 False 3 50;50;0 30.556 False ENSG00000113273 ENSG00000113273 HGNC:714 ARSE gene ARSE Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Chondrodysplasia punctata, X-linked recessive 302950 False 3 0;0;0 30.556 False ENSG00000157399 ENSG00000157399 HGNC:719 ARSE gene ARSE Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females CHONDRODYSPLASIA PUNCTATA 1, X-LINKED 12567415;9409863;7720070 False 3 33;67;0 30.556 False ENSG00000157399 ENSG00000157399 HGNC:719 ARSG gene ARSG Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Usher syndrome, type IV, OMIM:618144;usher syndrome, type 4, MONDO:0029141 26975023;20679209;25452429;33300174 False 3 67;0;33 30.556 False ENSG00000141337 ENSG00000141337 HGNC:24102 ARSK gene ARSK Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mucopolysaccharidosis, type X, OMIM:619698;mucopolysaccharidosis, type 10, MONDO:0030524 34916232;35959767;38292179 False 3 50;50;0 30.556 False ENSG00000164291 ENSG00000164291 HGNC:25239 ARV1 gene ARV1 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epileptic encephalopathy, early infantile, 38 25558065;27270415;26479315 False 3 67;33;0 30.556 False ENSG00000173409 ENSG00000173409 HGNC:29561 ARX gene ARX Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;UKGTN;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Epileptic encephalopathy, early infantile, 1, 308350Lissencephaly, X-linked 2, 300215Mental retardation, X-linked 29 and others, 300419Proud syndrome, 300004Partington syndrome, 309510Hydranencephaly with abnormal genitalia, 300215;MENTAL RETARDATION X-LINKED ARX-RELATED (MRXARX) False 3 100;0;0 30.556 False ENSG00000004848 ENSG00000004848 HGNC:18060 ASAH1 gene ASAH1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spinal muscular atrophy with progressive myoclonic epilepsy 159950, Farber lipogranulomatosis 228000, Fetal hydrops, Intellectual disability 27604308;29169047;22703880;24164096 False 3 0;0;0 30.556 False ENSG00000104763 ENSG00000104763 HGNC:735 ASAH1 gene ASAH1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal FARBER LIPOGRANULOMATOSIS 16951918;8955159;11241842;10610716 False 3 33;67;0 30.556 False ENSG00000104763 ENSG00000104763 HGNC:735 ASCC3 gene ASCC3 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder, autosomal recessive 81, OMIM:620700 21937992;26350204;35047834;39286456 False 3 25;0;75 30.556 False ENSG00000112249 ENSG00000112249 HGNC:18697 ASH1L gene ASH1L Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Mental retardation, autosomal dominant 52, 617796;intellectual disability 25961944;26350204;29276005;29753921;28191889 False 3 50;0;50 30.556 False ENSG00000116539 ENSG00000116539 HGNC:19088 ASL gene ASL London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Argininosuccinic aciduria, OMIM:207900;argininosuccinic aciduria, MONDO:0008815 27604308;12384776;17326097;29326055 False 3 0;0;0 30.556 False ENSG00000126522 ENSG00000126522 HGNC:746 ASL gene ASL Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Argininosuccinic aciduria, OMIM:207900;argininosuccinic aciduria, MONDO:0008815 12408190; 12384776 False 3 50;0;50 30.556 False ENSG00000126522 ENSG00000126522 HGNC:746 ASNS gene ASNS Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Asparagine synthetase deficiency, 615574;congenital microcephaly, intellectual disability, progressive cerebral atrophy, intractable seizures 24139043;25227173;30234940;27743885;29375865;2566342;27422383;27469131 False 3 0;100;0 30.556 False ENSG00000070669 ENSG00000070669 HGNC:753 ASPA gene ASPA Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal General Leukodystrophy & Mitochondrial Leukoencephalopathy, 25655951 25655951 False 3 0;0;0 30.556 False ENSG00000108381 ENSG00000108381 HGNC:756 ASPA gene ASPA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Canavan disease 27604308 False 3 0;0;0 30.556 False ENSG00000108381 ENSG00000108381 HGNC:756 ASPA gene ASPA Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Canavan disease, 271900;CANAVAN DISEASE False 3 100;0;0 30.556 False ENSG00000108381 ENSG00000108381 HGNC:756 ASPM gene ASPM Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly 5, primary, autosomal recessive, OMIM:608716 12355089;14574646;16673149;18452193;19028728;19353628;19770472;22775483;27250695;30500859 False 3 100;0;0 30.556 False ENSG00000066279 ENSG00000066279 HGNC:19048 ASS1 gene ASS1 Victorian Clinical Genetics Services;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Citrullinemia, 215700;intellectual disability 25529582;15266621;15334737;19006241 False 3 100;0;0 30.556 False ENSG00000130707 ENSG00000130707 HGNC:758 ASS1 gene ASS1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Citrullinaemia type1 (Urea cycle disorders and inherited hyperammonaemias);Citrullinemia 27604308 False 3 0;0;0 30.556 False ENSG00000130707 ENSG00000130707 HGNC:758 ASXL1 gene ASXL1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Bohring-Opitz syndrome, OMIM:605039;Bohring-Opitz syndrome, MONDO:0011510 21706002;22419483;25529582;24896178 False 3 100;0;0 30.556 False ENSG00000171456 ENSG00000171456 HGNC:18318 ASXL2 gene ASXL2 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Shashi-Pena syndrome 617190 27693232 False 3 100;0;0 30.556 False ENSG00000143970 ENSG00000143970 HGNC:23805 ASXL3 gene ASXL3 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Bainbridge-Ropers syndrome, OMIM:615485 23383720;26647312;28100473;34436830 False 3 0;100;0 30.556 False ENSG00000141431 ENSG00000141431 HGNC:29357 ATAD1 gene ATAD1 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperekplexia 4, OMIM:618011 28180185;29390050;29659736 False 3 100;0;0 30.556 False ENSG00000138138 ENSG00000138138 HGNC:25903 ATAD3A gene ATAD3A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Harel-Yoon syndrome, OMIM:617183;Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal, OMIM:618810 27640307 False 3 50;50;0 30.556 True ENSG00000197785 ENSG00000197785 HGNC:25567 ATAD3A gene ATAD3A Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Harel-Yoon syndrome 617183 27640307;25529582 False 3 100;0;0 30.556 False ENSG00000197785 ENSG00000197785 HGNC:25567 ATAD3A gene ATAD3A Expert Review Green;Literature;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Harel-Yoon syndrome, OMIM:617183;Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal, OMIM:618810;Lactic acidosis;Methylglutaconic aciduria 27640307 False 3 67;33;0 30.556 False ENSG00000197785 ENSG00000197785 HGNC:25567 ATG7 gene ATG7 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spinocerebellar ataxia, autosomal recessive 31, OMIM:619422 34161705 False 3 100;0;0 30.556 False ENSG00000197548 ENSG00000197548 HGNC:16935 ATIC gene ATIC Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal AICA-ribosiduria due to ATIC deficiency, 608688;AICA-RIBOSURIA (AICAR) False 3 100;0;0 30.556 False ENSG00000138363 ENSG00000138363 HGNC:794 ATIC gene ATIC London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;AICAR transformylase deficiency (Disorders of purine metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000138363 ENSG00000138363 HGNC:794 ATN1 gene ATN1 Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Congenital hypotonia, epilepsy, developmental delay, and digital anomalies, OMIM:618494 30827498 False 3 75;0;25 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000111676 ENSG00000111676 HGNC:3033 ATP11A gene ATP11A Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Leukodystrophy, hypomyelinating, 24, OMIM:619851 34403372;39432785 False 3 67;33;0 30.556 False ENSG00000068650 ENSG00000068650 HGNC:13552 ATP13A2 gene ATP13A2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal PARKINSON DISEASE 9 0 False 3 33;67;0 30.556 False ENSG00000159363 ENSG00000159363 HGNC:30213 ATP13A2 gene ATP13A2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Kufor-Rakeb syndrome False 3 0;0;0 30.556 False ENSG00000159363 ENSG00000159363 HGNC:30213 ATP1A1 gene ATP1A1 Expert Review Green;Literature;Expert Review Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Hypomagnesemia;Seizures;Intellectual disability 30388404 False 3 100;0;0 30.556 False ENSG00000163399 ENSG00000163399 HGNC:799 ATP1A2 gene ATP1A2 Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Migraine, familial hemiplegic, 2 602481;Alternating hemiplegia of childhood 1, 104290 15159495;29610157;33880529 False 3 50;0;50 30.556 False ENSG00000018625 ENSG00000018625 HGNC:800 ATP1A3 gene ATP1A3 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Alternating Hemiplegia of Childhood (AHC), intellectual disability 22842232;29396171;29291920;22842232;28969699;32802951;33880529 False 3 40;60;0 30.556 False ENSG00000105409 ENSG00000105409 HGNC:801 ATP2B1 gene ATP2B1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual developmental disorder, autosomal dominant 66, OMIM:619910 35358416;37926713 False 3 100;0;0 30.556 False ENSG00000070961 ENSG00000070961 HGNC:814 ATP5A1 gene ATP5A1 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4, OMIM: 615228;Combined oxidative phosphorylation deficiency 22, OMIM: 616045 23596069;23599390;34483339;34954817 False 3 75;25;0 30.556 True ENSG00000152234 ENSG00000152234 HGNC:823 ATP5A1 gene ATP5A1 Expert Review Green;London North GLH;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4, OMIM: 615228;Combined oxidative phosphorylation deficiency 22, OMIM: 616045 23596069;23599390;34483339;34954817 False 3 100;0;0 30.556 False ENSG00000152234 ENSG00000152234 HGNC:823 ATP5D gene ATP5D Expert Review Green;Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex V (ATP synthase) deficiency, 618120 29478781 False 3 0;0;0 30.556 False ENSG00000099624 ENSG00000099624 HGNC:837 ATP5D gene ATP5D Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex V (ATP synthase) deficiency, 618120 29478781 False 3 0;0;0 30.556 False ENSG00000099624 ENSG00000099624 HGNC:837 ATP5E gene ATP5E Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3, OMIM:614053;mitochondrial complex V (ATP synthase) deficiency nuclear type 3, MONDO:0013547 20566710;25954304;34954817 False 3 100;0;0 30.556 True ENSG00000124172 ENSG00000124172 HGNC:838 ATP5E gene ATP5E Expert Review Green;London North GLH;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3, OMIM:614053;mitochondrial complex V (ATP synthase) deficiency nuclear type 3, MONDO:0013547 20566710;27626380;25954304;27604308 False 3 100;0;0 30.556 False ENSG00000124172 ENSG00000124172 HGNC:838 ATP5G3 gene ATP5G3 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Dystonia, early-onset, and/or spastic paraplegia, OMIM:619681 34636445;34954817 False 3 67;33;0 30.556 False ENSG00000154518 ENSG00000154518 HGNC:843 ATP5G3 gene ATP5G3 Expert Review Green;NHS GMS;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Dystonia, early-onset, and/or spastic paraplegia, OMIM:619681 34636445;34954817 False 3 67;33;0 30.556 True ENSG00000154518 ENSG00000154518 HGNC:843 ATP5O gene ATP5O NHS GMS;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7, OMIM:620359 34954817;35621276 False 3 67;33;0 30.556 True ENSG00000241837 ENSG00000241837 HGNC:850 ATP5O gene ATP5O Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7, OMIM:620359 34954817;35621276 False 3 50;50;0 30.556 False ENSG00000241837 ENSG00000241837 HGNC:850 ATP6AP1 gene ATP6AP1 Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Immunodeficiency 47 27231034 False 3 0;0;0 30.556 False ENSG00000071553 ENSG00000071553 HGNC:868 ATP6AP2 gene ATP6AP2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked, syndromic, Hedera type, 300423;MENTAL RETARDATION X-LINKED WITH EPILEPSY;X-linked intellectual disability, Hedera type 26467484;15746149;29127204;25529582;11782983 False 3 40;20;40 30.556 False ENSG00000182220 ENSG00000182220 HGNC:18305 ATP6V0A1 gene ATP6V0A1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted ATP6V0A1-related developmental disorder (monoallelic) 30842224;33057194;34909687;33833240 False 3 75;25;0 30.556 False ENSG00000033627 ENSG00000033627 HGNC:865 ATP6V0A2 gene ATP6V0A2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal V0 subunit A2 of vesicular H(+)-ATPase deficiency (Disorders of multiple glycosylation and other glycosylation pathways, V-ATPase deficiencies);Cutis laxa, autosomal recessive, type IIA 21920;Wrinkly skin syndrome 278250 27604308 False 3 0;0;0 30.556 False ENSG00000185344 ENSG00000185344 HGNC:18481 ATP6V0A2 gene ATP6V0A2 Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cutis laxa, autosomal recessive, type IIA 219200; Wrinkly skin syndrome 278250 18157129; 22773132 False 3 33;0;67 30.556 False ENSG00000185344 ENSG00000185344 HGNC:18481 ATP6V0C gene ATP6V0C NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465 24623842;33090716;33190975;36074901;37161035 False 3 75;25;0 30.556 False ENSG00000185883 ENSG00000185883 HGNC:855 ATP6V1A gene ATP6V1A Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Developmental and epileptic encephalopathy 93, OMIM:618012 29668857;28065471 False 3 100;0;0 30.556 False ENSG00000114573 ENSG00000114573 HGNC:851 ATP6V1B2 gene ATP6V1B2 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted ZIMMERMANN-LABAND SYNDROME 25915598 False 3 0;100;0 30.556 False ENSG00000147416 ENSG00000147416 HGNC:854 ATP7A gene ATP7A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Menkes disease, 309400Occipital horn syndrome, 304150Spinal muscular atrophy, distal, X-linked 3, 300489;OCCIPITAL HORN SYNDROME False 3 100;0;0 30.556 False ENSG00000165240 ENSG00000165240 HGNC:869 ATP7A gene ATP7A London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Menkes disease False 3 0;0;0 30.556 False ENSG00000165240 ENSG00000165240 HGNC:869 ATP7B gene ATP7B London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Wilson disease 27604308 False 3 0;0;0 30.556 False ENSG00000123191 ENSG00000123191 HGNC:870 ATP8A2 gene ATP8A2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 OMIM:615268;cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 MONDO:0014104 22892528;27679995;30012219;29531481;31612321;20683487 False 3 25;0;75 30.556 False ENSG00000132932 ENSG00000132932 HGNC:13533 ATP8B1 gene ATP8B1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Cholestasis, progressive familial intrahepatic 1 211600;Cholestasis, benign recurrent intrahepatic 243300 AR;Cholestasis, intrahepatic, of pregnancy, 1 147480 AD;Byler disease (Disorders of bile acid metabolism and transport) 27604308 False 3 100;0;0 30.556 False ENSG00000081923 ENSG00000081923 HGNC:3706 ATP9A gene ATP9A Expert Review Green;Other;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Global developmental delay;Intellectual disability;Postnatal microcephaly;Failure to thrive;Abnormality of the abdomen;Neurodevelopmental disorder with poor growth and behavioral abnormalities, OMIM:620242 34379057;34764295;27626380 False 3 50;50;0 30.556 False ENSG00000054793 ENSG00000054793 HGNC:13540 ATPAF2 gene ATPAF2 Victorian Clinical Genetics Services;Emory Genetics Laboratory;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex V deficiency;Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1, 604273;Mitochondrial Complex V (ATP Synthase) Deficiency, Nuclear Type;Mitochondrial Diseases 14757859;19933271 False 3 50;50;0 30.556 False ENSG00000171953 ENSG00000171953 HGNC:18802 ATPAF2 gene ATPAF2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1, 604273;Complex V (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors);Mitochondrial Diseases;Isolated complex V deficiency;Mitochondrial Complex V (ATP Synthase) Deficiency, Nuclear Type 14757859;19933271 False 3 50;50;0 30.556 False ENSG00000171953 ENSG00000171953 HGNC:18802 ATR gene ATR Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Seckel syndrome 1, OMIM:210600 False 3 100;0;0 30.556 False ENSG00000175054 ENSG00000175054 HGNC:882 ATRX gene ATRX Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Alpha-thalassemia/mental retardation syndrome, 301040;Mental retardation-hypotonic facies syndrome, X-linked, 309580 25606380;17503331;16955409;25529582;24896178;26860117;26997013;10995512;7697714;12116232;15565397;8644709;9244431;9598720 False 3 100;0;0 30.556 False ENSG00000085224 ENSG00000085224 HGNC:886 ATXN7L3 gene ATXN7L3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown syndromic neurodevelopmental disorder 38753057;33731875 False 3 100;0;0 30.556 False ENSG00000087152 ENSG00000087152 HGNC:25416 AUH gene AUH Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-methylglutaconic aciduria, type I, OMIM:250950 20855850;17130438 False 3 100;0;0 30.556 False ENSG00000148090 ENSG00000148090 HGNC:890 AUH gene AUH Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-methylglutaconic aciduria, type I, 250950;3-METHYLGLUTACONIC ACIDURIA TYPE 1 False 3 100;0;0 30.556 False ENSG00000148090 ENSG00000148090 HGNC:890 AUH gene AUH London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-methylglutaconic aciduria, type I;Methylglutaconic aciduria type I (Organic acidurias) 27604308 False 3 0;0;0 30.556 False ENSG00000148090 ENSG00000148090 HGNC:890 AUTS2 gene AUTS2 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted SYNDROMIC INTELLECTUAL DISABILITY 23332918 False 3 100;0;0 30.556 False ENSG00000158321 ENSG00000158321 HGNC:14262 B3GALNT2 gene B3GALNT2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11 23453667 False 3 0;0;0 30.556 False ENSG00000162885 ENSG00000162885 HGNC:28596 B3GALNT2 gene B3GALNT2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 11 23453667 False 3 0;100;0 30.556 False ENSG00000162885 ENSG00000162885 HGNC:28596 B3GALT6 gene B3GALT6 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ehlers-Danlos syndrome, progeroid type, 2 23664117;23664118 False 3 0;0;0 30.556 False ENSG00000176022 ENSG00000176022 HGNC:17978 B3GAT3 gene B3GAT3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects 245600;B3GAT3-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) 27604308 False 3 0;0;0 30.556 False ENSG00000149541 ENSG00000149541 HGNC:923 B3GLCT gene B3GLCT London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peters-plus syndrome 261540;O-fucose-specific beta-1,3-N-glucosyltransferase deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies);O-fucose-specific beta-1,3-N-glucosyltransferase deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) 23889335;16909395 False 3 0;0;0 30.556 False ENSG00000187676 ENSG00000187676 HGNC:20207 B3GLCT gene B3GLCT Expert Review Green;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peters-plus syndrome, 261540 16909395 False 3 0;0;100 30.556 False ENSG00000187676 ENSG00000187676 HGNC:20207 B4GALNT1 gene B4GALNT1 Expert Review Green;Expert list;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 26, autosomal recessive OMIM:609195;hereditary spastic paraplegia 26 MONDO:0012213 23746551;24103911 False 3 100;0;0 30.556 False ENSG00000135454 ENSG00000135454 HGNC:4117 B4GALNT1 gene B4GALNT1 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 26, autosomal recessive, OMIM:609195;Hereditary spastic paraplegia 26, MONDO:0012213 23746551;24103911 False 3 100;0;0 30.556 False ENSG00000135454 ENSG00000135454 HGNC:4117 B4GALT1 gene B4GALT1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IId, OMIM:607091 11901181;21920538 False 3 0;0;0 30.556 False ENSG00000086062 ENSG00000086062 HGNC:924 B4GALT7 gene B4GALT7 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ehlers-Danlos syndrome, progeroid type, 1, 130070;EHLERS-DANLOS SYNDROME PROGEROID TYPE (EDSP) 3631078 False 3 33;0;67 30.556 False ENSG00000027847 ENSG00000027847 HGNC:930 B4GALT7 gene B4GALT7 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ehlers-Danlos syndrome with short stature and limb anomalies 130070;B4GALT7-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies, Disorders of protein O-glycosylation, O-xylosylglycan synthesis deficiencies);B4GALT7-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies);Beta-1,4-galactosyltransferase 7 deficiency (Disorders of protein O-glycosylation, O-xylosylglycan synthesis deficiencies) 27604308 False 3 0;0;0 30.556 False ENSG00000027847 ENSG00000027847 HGNC:930 B9D1 gene B9D1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Meckel syndrome 9, OMIM:614209;Meckel syndrome 9, MONDO:0013630;Joubert syndrome 27, OMIM:617120;Joubert syndrome 27, MONDO:0014927 21493627;24886560;25920555;32622957 False 3 60;40;0 30.556 False ENSG00000108641 ENSG00000108641 HGNC:24123 B9D2 gene B9D2 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Joubert syndrome 34, OMIM:614175;Meckel syndrome 10, OMIM:614175;Meckel syndrome, type 10, MONDO:0013609 26092869;21763481;31411728 False 3 100;0;0 30.556 False ENSG00000123810 ENSG00000123810 HGNC:28636 BAAT gene BAAT London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypercholanemia, familial 27604308;23415802 False 3 100;0;0 30.556 False ENSG00000136881 ENSG00000136881 HGNC:932 BAP1 gene BAP1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Kury-Isidor syndrome, OMIM:619762 35051358 False 3 100;0;0 30.556 False ENSG00000163930 ENSG00000163930 HGNC:950 BAZ2B gene BAZ2B Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 31999386;37872713 False 3 100;0;0 30.556 False ENSG00000123636 ENSG00000123636 HGNC:963 BBS1 gene BBS1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Bardet-Biedl syndrome 1 OMIM:209900;Bardet-Biedl syndrome 1 MONDO:0008854 25529582;24896178 False 3 100;0;0 30.556 False ENSG00000174483 ENSG00000174483 HGNC:966 BBS10 gene BBS10 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Bardet-Biedl syndrome 10, 209900;BARDET-BIEDL SYNDROME TYPE 10 (BBS10) False 3 100;0;0 30.556 False ENSG00000179941 ENSG00000179941 HGNC:26291 BBS12 gene BBS12 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Bardet-Biedl syndrome 12, 209900;BARDET-BIEDL SYNDROME TYPE 12 (BBS12) False 3 100;0;0 30.556 False ENSG00000181004 ENSG00000181004 HGNC:26648 BBS2 gene BBS2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Bardet-Biedl syndrome 2, 209900;BARDET-BIEDL SYNDROME TYPE 2 (BBS2) False 3 100;0;0 30.556 False ENSG00000125124 ENSG00000125124 HGNC:967 BBS4 gene BBS4 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Bardet-Biedl syndrome 4, 209900;BARDET-BIEDL SYNDROME TYPE 4 (BBS4) False 3 100;0;0 30.556 False ENSG00000140463 ENSG00000140463 HGNC:969 BBS5 gene BBS5 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Bardet-Biedl syndrome 5, 209900;BARDET-BIEDL SYNDROME TYPE 5 (BBS5) False 3 100;0;0 30.556 False ENSG00000163093 ENSG00000163093 HGNC:970 BBS7 gene BBS7 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Bardet-Biedl syndrome 7, 209900;BARDET-BIEDL SYNDROME TYPE 7 (BBS7) False 3 100;0;0 30.556 False ENSG00000138686 ENSG00000138686 HGNC:18758 BBS9 gene BBS9 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Bardet-Biedl syndrome 9, 209900;BARDET-BIEDL SYNDROME TYPE 9 (BBS9) False 3 100;0;0 30.556 False ENSG00000122507 ENSG00000122507 HGNC:30000 BCAP31 gene BCAP31 Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females DEAFNESS, DYSTONIA, AND CENTRAL HYPOMYELINATION WITH DISORGANIZATION OF THE GOLGI APPARATUS 24011989 False 3 33;67;0 30.556 False ENSG00000185825 ENSG00000185825 HGNC:16695 BCAP31 gene BCAP31 Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Deafness, dystonia and cerebellar hypomyelination, 300475 False 3 0;0;0 30.556 False ENSG00000185825 ENSG00000185825 HGNC:16695 BCAS3 gene BCAS3 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Syndromic neurodevelopmental disorder 34022130 False 3 100;0;0 30.556 False ENSG00000141376 ENSG00000141376 HGNC:14347 BCAT2 gene BCAT2 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Branched-chain amino acid transferase (Disorder of branched-chain amino acid metabolism not classified as organic aciduria) 27604308;14755340;25653144 False 3 50;0;50 30.556 False ENSG00000105552 ENSG00000105552 HGNC:977 BCKDHA gene BCKDHA Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Maple syrup urine disease, type Ia, 248600;MAPLE SYRUP URINE DISEASE False 3 100;0;0 30.556 False ENSG00000248098 ENSG00000248098 HGNC:986 BCKDHA gene BCKDHA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Maple syrup urine disease, type Ia;BCKD E1 alpha subunit of deficiency (Maple syrup urine disease, disorder of branched-chain amino acid metabolism not classified as organic aciduria) 27604308 False 3 0;0;0 30.556 False ENSG00000248098 ENSG00000248098 HGNC:986 BCKDHB gene BCKDHB London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Maple syrup urine disease, type Ib;BCKD E1 beta subunit of deficiency (Maple syrup urine disease, disorder of branched-chain amino acid metabolism not classified as organic aciduria) 27604308 False 3 0;0;0 30.556 False ENSG00000083123 ENSG00000083123 HGNC:987 BCKDHB gene BCKDHB Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Maple syrup urine disease, type Ib, 248600;MAPLE SYRUP URINE DISEASE False 3 100;0;0 30.556 False ENSG00000083123 ENSG00000083123 HGNC:987 BCKDK gene BCKDK Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Branched-chain ketoacid dehydrogenase kinase deficiency 27604308;22956686 False 3 100;0;0 30.556 False ENSG00000103507 ENSG00000103507 HGNC:16902 BCKDK gene BCKDK Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Branched-chain ketoacid dehydrogenase kinase deficiency, 614923;Intellectual disability 22956686;24449431 False 3 100;0;0 30.556 False ENSG00000103507 ENSG00000103507 HGNC:16902 BCL11A gene BCL11A Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted INTELLECTUAL DISABILITY 25533962 False 3 100;0;0 30.556 False ENSG00000119866 ENSG00000119866 HGNC:13221 BCL11B gene BCL11B Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual disability;Intellectual developmental disorder with dysmorphic facies, speech delay, and T-cell abnormalities, 618092 27959755;29985992 False 3 100;0;0 30.556 False ENSG00000127152 ENSG00000127152 HGNC:13222 BCOR gene BCOR Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Microphthalmia, syndromic 2, 300166;MICROPHTHALMIA SYNDROMIC TYPE 2 (MCOPS2) False 3 100;0;0 30.556 False ENSG00000183337 ENSG00000183337 HGNC:20893 BCS1L gene BCS1L London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Complex III (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors);Mitochondrial Diseases;Isolated complex III deficiency;Mitochondrial Respiratory Chain Complex III Deficiency;Mitochondrial complex III deficiency, nuclear type 1, 124000;Leigh syndrome, 256000;Bjornstad syndrome, 262000;GRACILE syndrome, 603358 27604308 False 3 100;0;0 30.556 False ENSG00000074582 ENSG00000074582 HGNC:1020 BCS1L gene BCS1L Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex III disorders;Mitochondrial Leukoencephalopathy 25655951 False 3 0;0;0 30.556 False ENSG00000074582 ENSG00000074582 HGNC:1020 BCS1L gene BCS1L Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex III deficiency, nuclear type 1, 124000;Leigh syndrome, 256000;Bjornstad syndrome, 262000 24896178;26503795; 17403714; 9777342 False 3 50;0;50 30.556 False ENSG00000074582 ENSG00000074582 HGNC:1020 BCS1L gene BCS1L Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex III deficiency;Mitochondrial complex III deficiency, nuclear type 1, 124000;Leigh syndrome, 256000;Bjornstad syndrome, 262000;GRACILE syndrome, 603358;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex III Deficiency False 3 100;0;0 30.556 False ENSG00000074582 ENSG00000074582 HGNC:1020 BICRA gene BICRA Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental delay, intellectual disability, autism spectrum disorder,behavioral abnormalities, dysmorphic features 33232675 False 3 100;0;0 30.556 False ENSG00000063169 ENSG00000063169 HGNC:4332 BLM gene BLM Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Bloom syndrome, OMIM:210900 22514588;23552953;36646944 False 3 75;0;25 30.556 False ENSG00000197299 ENSG00000197299 HGNC:1058 BLOC1S1 gene BLOC1S1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal severe intellectual disability;severe global developmental delay;epilepsy 33875846 False 3 100;0;0 30.556 False ENSG00000135441 ENSG00000135441 HGNC:4200 BLOC1S1 gene BLOC1S1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal severe intellectual disability;severe global developmental delay;epilepsy 33875846 False 3 100;0;0 30.556 False ENSG00000135441 ENSG00000135441 HGNC:4200 BMP4 gene BMP4 Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Microphthalmia, syndromic 6 607932;Global developmental delay False 3 100;0;0 30.556 False ENSG00000125378 ENSG00000125378 HGNC:1071 BOLA3 gene BOLA3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperglycinaemia, non-ketotic (Baker (2014) Brain 137,366);Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Multiple mitochondrial dysfunctions syndrome 2, 614299;Multiple Mitochondrial Dysfunctions Syndrome;Disorders of iron homeostasis 27604308 False 3 100;0;0 30.556 False ENSG00000163170 ENSG00000163170 HGNC:24415 BOLA3 gene BOLA3 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia, OMIM:614299 29654549;29501406;24334290;21944046;30302924 False 3 100;0;0 30.556 False ENSG00000163170 ENSG00000163170 HGNC:24415 BOLA3 gene BOLA3 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 2 11156534 False 3 0;100;0 30.556 False ENSG00000163170 ENSG00000163170 HGNC:24415 BOLA3 gene BOLA3 Victorian Clinical Genetics Services;Expert Review Green;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of iron homeostasis;Multiple mitochondrial dysfunctions syndrome 2, 614299;Hyperglycinaemia, non-ketotic (Baker (2014) Brain 137,366);Multiple Mitochondrial Dysfunctions Syndrome False 3 100;0;0 30.556 True ENSG00000163170 ENSG00000163170 HGNC:24415 BORCS8 gene BORCS8 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities, OMIM:620987 38128568 False 3 100;0;0 30.556 False ENSG00000254901 ENSG00000254901 HGNC:37247 BPTF gene BPTF Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies, 617755;intellectual disability 28942966 False 3 100;0;0 30.556 False ENSG00000171634 ENSG00000171634 HGNC:3581 BRAF gene BRAF Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Melanoma, malignant, somaticColorectal cancer, somaticAdenocarcinoma of lung, somatic, 211980Nonsmall cell lung cancer, somaticCardiofaciocutaneous syndrome, 115150Noonan syndrome 7, 613706LEOPARD syndrome 3, 613707;NOONAN SYNDROME TYPE 7 (NS7) False 3 100;0;0 30.556 False ENSG00000157764 ENSG00000157764 HGNC:1097 BRAT1 gene BRAT1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal LETHAL NEONATAL RIGIDITY AND SEIZURE SYNDROME 22279524 False 3 50;50;0 30.556 False ENSG00000106009 ENSG00000106009 HGNC:21701 BRD4 gene BRD4 Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Cornelia de Lange syndrome 6, OMIM:620568 29379197;30055032;30302754 False 3 100;0;0 30.556 False ENSG00000141867 ENSG00000141867 HGNC:13575 BRF1 gene BRF1 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cerebellofaciodental syndrome, 616202;intellectual disability 25561519 False 3 100;0;0 30.556 False ENSG00000185024 ENSG00000185024 HGNC:11551 BRPF1 gene BRPF1 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual developmental disorder with dysmorphic facies and ptosis 617333 27939640 False 3 100;0;0 30.556 False ENSG00000156983 ENSG00000156983 HGNC:14255 BRSK2 gene BRSK2 Expert Review;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Global developmental delay;Autism;Behavioral abnormality;Global developmental delay, Intellectual disability, Autism, Behavioral abnormality;Intellectual disability 15705853;23715323;30879638;25363768;28135719 False 3 100;0;0 30.556 False ENSG00000174672 ENSG00000174672 HGNC:11405 BRWD3 gene BRWD3 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental Retardation, X-linked;Mental retardation, X-linked 93, 300659;MENTAL RETARDATION X-LINKED TYPE 93 (MRX93) False 3 100;0;0 30.556 False ENSG00000165288 ENSG00000165288 HGNC:17342 BSCL2 gene BSCL2 NHS GMS;Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Encephalopathy, progressive, with or without lipodystrophy, OMIM:615924;Lipodystrophy, congenital generalized, type 2, OMIM:269700 24896178;26503795;23564749; 15181077 False 3 50;0;50 30.556 False ENSG00000168000 ENSG00000168000 HGNC:15832 BTD gene BTD London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Biotinidase deficiency (Disorders of biotin metabolism);Biotinidase deficiency;lactic acidosis with seizures and eczema,immune deficiency 27604308 False 3 0;0;100 30.556 False ENSG00000169814 ENSG00000169814 HGNC:1122 BTD gene BTD Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Biotinidase deficiency, 253260;BIOTINIDASE DEFICIENCY False 3 100;0;0 30.556 False ENSG00000169814 ENSG00000169814 HGNC:1122 BTD gene BTD Expert Review Green;NHS GMS;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Biotinidase deficiency, OMIM:253260;biotinidase deficiency, MONDO:0009665 False 3 25;50;25 30.556 True ENSG00000169814 ENSG00000169814 HGNC:1122 BUB1 gene BUB1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly 30, primary, autosomal recessive, OMIM:620183 35044816 False 3 67;33;0 30.556 False ENSG00000169679 ENSG00000169679 HGNC:1148 BUB1B gene BUB1B Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Colorectal cancer, somatic, 114500Mosaic variegated aneuploidy syndrome 1, 257300[Premature chromatid separation trait], 176430;MOSAIC VARIEGATED ANEUPLOIDY SYNDROME 1; MVA1 False 3 100;0;0 30.556 False ENSG00000156970 ENSG00000156970 HGNC:1149 C12orf4 gene C12orf4 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder, autosomal recessive 66, OMIM:618221 27311568;25558065 False 3 100;0;0 30.556 False ENSG00000047621 ENSG00000047621 HGNC:1184 C12orf57 gene C12orf57 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Temtamy syndrome, 218340;TEMTAMY SYNDROME; COLOBOMA, HYPOPLASTIC CORPUS CALLOSUM AND INTELLECTUAL DISABILITY False 3 100;0;0 30.556 False ENSG00000111678 ENSG00000111678 HGNC:29521 C12orf65 gene C12orf65 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 7, OMIM:613559;Spastic paraplegia 55, autosomal recessive, OMIM:615035 20598281 False 3 33;67;0 30.556 False ENSG00000130921 ENSG00000130921 HGNC:26784 C12orf65 gene C12orf65 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 7, OMIM:613559;Spastic paraplegia 55, autosomal recessive, OMIM:615035;Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Multiple respiratory chain complex deficiencies (disorders of protein synthesis) 27604308 False 3 100;0;0 30.556 False ENSG00000130921 ENSG00000130921 HGNC:26784 C12orf65 gene C12orf65 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 7, OMIM:613559;Spastic paraplegia 55, autosomal recessive, OMIM:615035 False 3 100;0;0 30.556 True ENSG00000130921 ENSG00000130921 HGNC:26784 C12orf66 gene C12orf66 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder, autosomal recessive 83, OMIM:621100 39824192 False 3 100;0;0 30.556 False ENSG00000174206 ENSG00000174206 HGNC:26517 C19orf12 gene C19orf12 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal ?Spastic paraplegia 43, autosomal recessive, OMIM:615043;Neurodegeneration with brain iron accumulation 4, OMIM: 614298 27604308;21981780;29295770;31087512 False 3 25;0;75 30.556 False ENSG00000131943 ENSG00000131943 HGNC:25443 C19orf70 gene C19orf70 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 37, 618329 29618761;27485409;27623147 False 3 0;0;0 30.556 False ENSG00000174917 ENSG00000174917 HGNC:33702 C19orf70 gene C19orf70 Expert Review Green;Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 37, 618329 27623147;29618761;27485409 False 3 0;0;0 30.556 False ENSG00000174917 ENSG00000174917 HGNC:33702 C1QBP gene C1QBP Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 33, MIM#617713 28942965 False 3 100;0;0 30.556 True ENSG00000108561 ENSG00000108561 HGNC:1243 C1QBP gene C1QBP Expert Review Green;Expert Review;Literature;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 33 617713 28942965 False 3 100;0;0 30.556 False ENSG00000108561 ENSG00000108561 HGNC:1243 C2CD3 gene C2CD3 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Orofaciodigital syndrome XIV, 615948;Joubert-related disorder 24997988;26092869;26477546;27094867;30097616 False 3 25;75;0 30.556 False ENSG00000168014 ENSG00000168014 HGNC:24564 C2orf69 gene C2orf69 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 53, OMIM:619423 34038740;33945503 False 3 100;0;0 30.556 False ENSG00000178074 ENSG00000178074 HGNC:26799 C2orf69 gene C2orf69 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 53, OMIM:619423 34038740;33945503 False 3 100;0;0 30.556 False ENSG00000178074 ENSG00000178074 HGNC:26799 C2orf69 gene C2orf69 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 53, OMIM:619423 34038740;33945503 False 3 100;0;0 30.556 False ENSG00000178074 ENSG00000178074 HGNC:26799 C2orf69 gene C2orf69 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 53, OMIM:619423 34038740;33945503 False 3 100;0;0 30.556 False ENSG00000178074 ENSG00000178074 HGNC:26799 C5orf42 gene C5orf42 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal JOUBERT SYNDROME False 3 100;0;0 30.556 False ENSG00000197603 ENSG00000197603 HGNC:25801 CA2 gene CA2 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, 259730;OSTEOPETROSIS AUTOSOMAL RECESSIVE TYPE 3 (OPTB3);carbonic anhydrase II deficiency;intellectual disability 25529582;24896178;12566520;1301935;8127074;5041390;16265785;28509178;15300855;8834238;1928091 False 3 80;0;20 30.556 False ENSG00000104267 ENSG00000104267 HGNC:1373 CA5A gene CA5A Expert Review Green;NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperammonemia due to carbonic anhydrase VA deficiency;Hyperammonemia (Urea cycle disorders and inherited hyperammonaemias) 27604308 False 3 100;0;0 30.556 False ENSG00000174990 ENSG00000174990 HGNC:1377 CA5A gene CA5A Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperammonemia due to carbonic anhydrase VA deficiency, 615751 26913920;24530203 False 3 0;0;0 30.556 False ENSG00000174990 ENSG00000174990 HGNC:1377 CA8 gene CA8 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cerebellar ataxia and mental retardation with or without quadrupedal locomotion 3, 613227;CEREBELLAR ATAXIA MENTAL RETARDATION AND DYSEQUILIBRIUM SYNDROME TYPE 3 (CMARQ3) False 3 100;0;0 30.556 False ENSG00000178538 ENSG00000178538 HGNC:1382 CACNA1A gene CACNA1A NHS GMS;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Developemental and epileptic encephalopathy 42, OMIM:617106;developmental and epileptic encephalopathy, 42, MONDO:0014917 24896178;27476654;36063114;34267336;33445191;27250579 False 3 50;0;50 30.556 False ENSG00000141837 ENSG00000141837 HGNC:1388 CACNA1B gene CACNA1B Expert Review;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements, 618497;Progressive Epilepsy-Dyskinesia;Seizures;Abnormality of movement;Intellectual disability;Developmental regression;Global developmental delay 26157024;30982612 False 3 100;0;0 30.556 False ENSG00000148408 ENSG00000148408 HGNC:1389 CACNA1C gene CACNA1C Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Timothy syndrome, OMIM:601005;Timothy syndrome, MONDO:0010979;Long QT syndrome 8, OMIM:618447;long qt syndrome 8, MONDO:0032756;Brugada syndrome 3, OMIM:611875;Brugada syndrome 3, MONDO:0012742;CACNA1C-related disorder 24896178;15454078;28371864 False 3 50;0;50 30.556 False ENSG00000151067 ENSG00000151067 HGNC:1390 CACNA1D gene CACNA1D Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Primary aldosteronism, seizures, and neurologic abnormalities 615474 AD; Sinoatrial node dysfunction and deafness 614896 AR 28472301; 23913001 False 3 33;67;0 30.556 False ENSG00000157388 ENSG00000157388 HGNC:1391 CACNA1E gene CACNA1E Expert Review Green;Literature;Expert Review Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Global developmental delay;Intellectual disability;Seizures;Dystonia;Congenital contracture;Macrocephaly;Epileptic encephalopathy, early infantile, 69, 618285 29942082;30343943 False 3 100;0;0 30.556 False Other ENSG00000198216 ENSG00000198216 HGNC:1392 CACNA1G gene CACNA1G Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Spinocerebellar ataxia 42 616795;Cerebellar atrophy, epilepsy, intellectual disability 24896178;26350204;21937992;29878067 False 3 25;0;75 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000006283 ENSG00000006283 HGNC:1394 CACNA1I gene CACNA1I Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with speech impairment and with or without seizures, OMIM:620114 33704440 False 3 100;0;0 30.556 False Other ENSG00000100346 ENSG00000100346 HGNC:1396 CACNA2D1 gene CACNA2D1 Expert Review Green;NHS GMS;Other;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Abnormal muscle tone;Feeding difficulties;Global developmental delay;Intellectual disability;Seizures;Microcephaly;Abnormality of the corpus callosum;Cerebral atrophy;Abnormality of movement;Cortical visual impairment;Pain insensitivity 35293990;28097321;34356170 False 3 100;0;0 30.556 False ENSG00000153956 ENSG00000153956 HGNC:1399 CAD gene CAD Expert Review Green;Literature;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental and epileptic encephalopathy 50, OMIM:616457 25678555;28007989;30914295 False 3 0;100;0 30.556 False ENSG00000084774 ENSG00000084774 HGNC:1424 CAMK2A gene CAMK2A Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Mental retardation, autosomal dominant 53, OMIM:617798;?Mental retardation, autosomal recessive 63, OMIM:618095 26350204;29100089;29784083 False 3 33;0;67 30.556 False ENSG00000070808 ENSG00000070808 HGNC:1460 CAMK2B gene CAMK2B Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Mental retardation, autosomal dominant 54, OMIM:617799 29100089;29560374;30842224;32875707 False 3 100;0;0 30.556 False ENSG00000058404 ENSG00000058404 HGNC:1461 CAMK2D gene CAMK2D Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 38272033 False 3 100;0;0 30.556 False ENSG00000145349 ENSG00000145349 HGNC:1462 CAMK4 gene CAMK4 Expert Review Green;Other;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Global developmental delay;Intellectual disability;Autism;Behavioral abnormality;Abnormality of movement;Dystonia;Ataxia;Chorea;Myoclonus 30262571;33098801;33211350 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000152495 ENSG00000152495 HGNC:1464 CAMSAP1 gene CAMSAP1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cortical dysplasia, complex, with other brain malformations 12, OMIM:620316 36283405 False 3 100;0;0 30.556 False ENSG00000130559 ENSG00000130559 HGNC:19946 CAMTA1 gene CAMTA1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted CEREBELLAR ATAXIA, NONPROGRESSIVE, WITH MENTAL RETARDATION 22693284 False 3 100;0;0 30.556 False ENSG00000171735 ENSG00000171735 HGNC:18806 CAPN15 gene CAPN15 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Oculogastrointestinal neurodevelopmental syndrome, OMIM:619318 33410501;32885237 False 3 100;0;0 30.556 False ENSG00000103326 ENSG00000103326 HGNC:11182 CAPRIN1 gene CAPRIN1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636 23849776;35979925;36136249;35977029;28135719;31398340 False 3 50;0;50 30.556 False ENSG00000135387 ENSG00000135387 HGNC:6743 CARS gene CARS Expert Review;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly, developmental delay, and brittle hair syndrome, OMIM:618891 30824121 False 3 100;0;0 30.556 False ENSG00000110619 ENSG00000110619 HGNC:1493 CARS2 gene CARS2 Expert Review Green;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);No OMIM phenotype;Combined oxidative phosphorylation deficiency 27 616672 25361775;25787132;30139652 False 3 100;0;0 30.556 False ENSG00000134905 ENSG00000134905 HGNC:25695 CARS2 gene CARS2 Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 27 616672;Multiple respiratory chain complex deficiencies (disorders of protein synthesis);No OMIM phenotype 25361775;25787132;30139652 False 3 100;0;0 30.556 False ENSG00000134905 ENSG00000134905 HGNC:25695 CASK gene CASK Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Mental retardation and microcephaly with pontine and cerebellar hypoplasia, 300749FG syndrome 4, 300422Mental retardation, with or without nystagmus, 300422;MENTAL RETARDATION X-LINKED CASK-RELATED (MRXCASK) 21954287;20595373;32700313;33090494;33272775;35149592 False 3 100;0;0 30.556 False ENSG00000147044 ENSG00000147044 HGNC:1497 CASP2 gene CASP2 NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, OMIM:620653 21937992;24896178;26350204;37880421 False 3 60;0;40 30.556 False ENSG00000106144 ENSG00000106144 HGNC:1503 CAT gene CAT London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Acatalasaemia (Other peroxisomal disorders);Acatalasemia, 614097 27604308 False 3 0;0;0 30.556 False ENSG00000121691 ENSG00000121691 HGNC:1516 CBL gene CBL Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, 613563;NOONAN SYNDROME-LIKE DISORDER WITH OR WITHOUT JUVENILE MEYLOMONOCYTIC LEUKEMIA False 3 100;0;0 30.556 False ENSG00000110395 ENSG00000110395 HGNC:1541 CBS gene CBS Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Homocystinuria, B6-responsive and nonresponsive types, 236200;Thrombosis, hyperhomocysteinemic, 236200;CYSTATHIONINE BETA-SYNTHASE DEFICIENCY (CBSD) False 3 100;0;0 30.556 False ENSG00000160200 ENSG00000160200 HGNC:1550 CBS gene CBS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Homocystinuria, B6-responsive and nonresponsive types False 3 0;0;0 30.556 False ENSG00000160200 ENSG00000160200 HGNC:1550 CC2D1A gene CC2D1A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder, autosomal recessive 3, OMIM:608443 16033914;30500859 False 3 100;0;0 30.556 False ENSG00000132024 ENSG00000132024 HGNC:30237 CC2D2A gene CC2D2A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Joubert syndrome 9, 612285Meckel syndrome 6, 612284COACH syndrome, 216360;MECKEL SYNDROME, TYPE 6; MKS6 False 3 100;0;0 30.556 False ENSG00000048342 ENSG00000048342 HGNC:29253 CCBE1 gene CCBE1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hennekam lymphangiectasia-lymphedema syndrome 1, OMIM:235510 False 3 100;0;0 30.556 False ENSG00000183287 ENSG00000183287 HGNC:29426 CCDC115 gene CCDC115 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIo 616828 26833332 False 3 0;0;0 30.556 False ENSG00000136710 ENSG00000136710 HGNC:28178 CCDC22 gene CCDC22 Victorian Clinical Genetics Services;Expert Review Green;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females SYNDROMIC X-LINKED INTELLECTUAL DISABILITY False 3 100;0;0 30.556 False ENSG00000101997 ENSG00000101997 HGNC:28909 CCDC32 gene CCDC32 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cardiofacioneurodevelopmental syndrome, OMIM:619123;cardiofacioneurodevelopmental syndrome, MONDO:0030873 32307552;35451546 False 3 50;50;0 30.556 False ENSG00000128891 ENSG00000128891 HGNC:28295 CCDC47 gene CCDC47 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Trichohepatoneurodevelopmental syndrome, OMIM:618268 30401460 False 3 100;0;0 30.556 False ENSG00000108588 ENSG00000108588 HGNC:24856 CCDC82 gene CCDC82 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 27457812;28397838;35118659;35373332 False 3 67;33;0 30.556 False ENSG00000149231 ENSG00000149231 HGNC:26282 CCDC88A gene CCDC88A Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal PEHO syndrome-like, OMIM:617507 26917597;30392057;37798908;39334473;39273517 False 3 33;67;0 30.556 False ENSG00000115355 ENSG00000115355 HGNC:25523 CCDC88C gene CCDC88C Expert Review Green;Victorian Clinical Genetics Services;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Spinocerebellar ataxia 40 616053 AD; Hydrocephalus, nonsyndromic, autosomal recessive 236600 AR 23042809; 21031079 False 3 100;0;0 30.556 False ENSG00000015133 ENSG00000015133 HGNC:19967 CCND2 gene CCND2 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 0 False 3 33;67;0 30.556 False ENSG00000118971 ENSG00000118971 HGNC:1583 CCT6A gene CCT6A Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder, MONDO:0700092 39480921 False 3 100;0;0 30.556 False ENSG00000146731 ENSG00000146731 HGNC:1620 CDC42 gene CDC42 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Takenouchi-Kosaki syndrome, 616737;Intellectual disability 26386261;26708094;29394990 False 3 0;0;0 30.556 False ENSG00000070831 ENSG00000070831 HGNC:1736 CDC6 gene CDC6 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Meier-Gorlin syndrome 5, OMIM:613805 11477602 False 3 33;67;0 30.556 False ENSG00000094804 ENSG00000094804 HGNC:1744 CDH11 gene CDH11 Literature;Expert Review Green;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Elsahy-Waters syndrome, OMIM:211380;Teebi hypertelorism syndrome 27431290;28988429;29271567;33811546 False 3 100;0;0 30.556 False ENSG00000140937 ENSG00000140937 HGNC:1750 CDH2 gene CDH2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, OMIM:618929;Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MONDO:0030065 31585109;9015265;17222817;31650526 False 3 60;40;0 30.556 False ENSG00000170558 ENSG00000170558 HGNC:1759 CDK10 gene CDK10 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Al Kaissi syndrome, 617694;intellectual disability 28886341 False 3 100;0;0 30.556 False ENSG00000185324 ENSG00000185324 HGNC:1770 CDK13 gene CDK13 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Congenital heart defects, dysmorphic facial features, and intellectual development disorder 617360 27479907 False 3 100;0;0 30.556 False Other - please provide details in the comments ENSG00000065883 ENSG00000065883 HGNC:1733 CDK16 gene CDK16 NHS GMS;Expert Review Green;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Intellectual disability, MONDO:0001071 26350204;25644381;31981491;36323681 False 3 33;0;67 30.556 False ENSG00000102225 ENSG00000102225 HGNC:8749 CDK19 gene CDK19 NHS GMS;Expert Review Green;Literature;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Epileptic encephalopathy, early infantile, 87 618916 20563892;32330417 False 3 100;0;0 30.556 False ENSG00000155111 ENSG00000155111 HGNC:19338 CDK5RAP2 gene CDK5RAP2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly 3, primary, autosomal recessive, 604804;PRIMARY AUTOSOMAL RECESSIVE MICROCEPHALY False 3 100;0;0 30.556 False ENSG00000136861 ENSG00000136861 HGNC:18672 CDK8 gene CDK8 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual developmental disorder with hypotonia and behavioral abnormalities, OMIM:618748 26350204;24139904;30905399 False 3 25;0;75 30.556 False ENSG00000132964 ENSG00000132964 HGNC:1779 CDK9 gene CDK9 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Global developmental delay HP:0001263;syndromic intellectual disability MONDO:0000508 26633546;30237576;29302074;33640901 False 3 100;0;0 30.556 False ENSG00000136807 ENSG00000136807 HGNC:1780 CDKL5 gene CDKL5 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Epileptic encephalopathy, early infantile, 2, 300672Angelman syndrome-like, 105830;EPILEPTIC ENCEPHALOPATHY EARLY INFANTILE TYPE 2 (EIEE2) False 3 100;0;0 30.556 False ENSG00000008086 ENSG00000008086 HGNC:11411 CDON gene CDON Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Holoprosencephaly 11, 614226;HOLOPROSENCEPHALY 11 False 3 100;0;0 30.556 False ENSG00000064309 ENSG00000064309 HGNC:17104 CELF2 gene CELF2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental and epileptic encephalopathy 97, OMIM:619561 34107259;33131106 False 3 100;0;0 30.556 False Other ENSG00000048740 ENSG00000048740 HGNC:2550 CENPF gene CENPF Victorian Clinical Genetics Services;Expert Review Green;Other Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Stromme syndrome, OMIM:243605;Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome False 3 0;0;0 30.556 False ENSG00000117724 ENSG00000117724 HGNC:1857 CENPJ gene CENPJ Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly 6, primary, autosomal recessive, 608393Seckel syndrome 4, 613676;MICROCEPHALY PRIMARY TYPE 6 (MCPH6) False 3 100;0;0 30.556 False ENSG00000151849 ENSG00000151849 HGNC:17272 CEP104 gene CEP104 Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Joubert syndrome 25, 616781 26477546;31625690 False 3 100;0;0 30.556 False ENSG00000116198 ENSG00000116198 HGNC:24866 CEP120 gene CEP120 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Joubert syndrome 31 (617761);Short-rib thoracic dysplasia 13 with or without polydactyly (616300) 27208211 False 3 100;0;0 30.556 False ENSG00000168944 ENSG00000168944 HGNC:26690 CEP135 gene CEP135 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly 8, primary, autosomal recessive, 614673;PRIMARY MICROCEPHALY AND DISTURBED CENTROSOMAL FUNCTION False 3 100;0;0 30.556 False ENSG00000174799 ENSG00000174799 HGNC:29086 CEP152 gene CEP152 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly 9, primary, autosomal recessive, 614852Seckel syndrome 5, 613823;MICROCEPHALY PRIMARY TYPE 4 (MCPH4) False 3 100;0;0 30.556 False ENSG00000103995 ENSG00000103995 HGNC:29298 CEP290 gene CEP290 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Joubert syndrome 5, 610188Senior-Loken syndrome 6, 610189Leber congenital amaurosis 10, 611755Meckel syndrome 4, 611134Bardet-Biedl syndrome 14, 209900;BARDET-BIEDL SYNDROME TYPE 14 (BBS14) False 3 100;0;0 30.556 False ENSG00000198707 ENSG00000198707 HGNC:29021 CEP41 gene CEP41 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Joubert syndrome 15, 614464;JOUBERT SYNDROME 15 False 3 100;0;0 30.556 False ENSG00000106477 ENSG00000106477 HGNC:12370 CEP55 gene CEP55 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal microcephaly, delayed development, and bilateral toe syndactyly 32100459 False 3 0;0;0 30.556 False ENSG00000138180 ENSG00000138180 HGNC:1161 CEP57 gene CEP57 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MOSAIC VARIEGATED ANEUPLOIDY SYNDROME 2 21552266;12116237 False 3 33;67;0 30.556 False ENSG00000166037 ENSG00000166037 HGNC:30794 CEP83 gene CEP83 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal INFANTILE NEPHRONOPHTHISIS AND INTELLECTUAL DISABILITY 24882706 False 3 100;0;0 30.556 False ENSG00000173588 ENSG00000173588 HGNC:17966 CEP85L gene CEP85L Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Lissencephaly 10, OMIM:618873;Lissencephaly 10, MONDO:0030031 32097629;32097630 False 3 100;0;0 30.556 False ENSG00000111860 ENSG00000111860 HGNC:21638 CHAMP1 gene CHAMP1 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579 35271727 False 3 100;0;0 30.556 False ENSG00000198824 ENSG00000198824 HGNC:20311 CHCHD10 gene CHCHD10 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Frontotemporal dementia and/or amyotrophic lateral sclerosis 2;?Myopathy, isolated mitochondrial, autosomal dominant, 616209;Spinal muscular atrophy, Jokela type 31261376 False 3 100;0;0 30.556 False ENSG00000250479 ENSG00000250479 HGNC:15559 CHCHD10 gene CHCHD10 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted ?Myopathy, isolated mitochondrial, autosomal dominant, 616209;Frontotemporal dementia and/or amyotrophic lateral sclerosis 2;Spinal muscular atrophy, Jokela type False 3 100;0;0 30.556 False ENSG00000250479 ENSG00000250479 HGNC:15559 CHD2 gene CHD2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Epileptic encephalopathy, childhood-onset, 615369;EPILEPTIC ENCEPHALOPATHY False 3 100;0;0 30.556 False ENSG00000173575 ENSG00000173575 HGNC:1917 CHD3 gene CHD3 Expert Review Green;Literature;Expert Review Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Global developmental delay;Intellectual disability;Macrocephaly;Snijders Blok-Campeau syndrome, 618205 30397230;29463886 False 3 100;0;0 30.556 False ENSG00000170004 ENSG00000170004 HGNC:1918 CHD4 gene CHD4 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Sifrim-Hitz-Weiss syndrome OMIM:617159;Sifrim-Hitz-Weiss syndrome MONDO:0014946 False 3 100;0;0 30.556 False ENSG00000111642 ENSG00000111642 HGNC:1919 CHD5 gene CHD5 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Parenti-Mignot neurodevelopmental syndrome, OMIM:610771;Intellectual disability, MONDO:0001071;Epilepsy, MONDO:0005027 33944996 False 3 100;0;0 30.556 False ENSG00000116254 ENSG00000116254 HGNC:16816 CHD7 gene CHD7 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted CHARGE syndrome, 214800{Scoliosis, idiopathic 3}, 608765Hypogonadotropic hypogonadism 5 with or without anosmia, 612370;KALLMANN SYNDROME TYPE 5 (KAL5) False 3 100;0;0 30.556 False ENSG00000171316 ENSG00000171316 HGNC:20626 CHD8 gene CHD8 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Overgrowth with Intellectual disability 23160955 False 3 100;0;0 30.556 False ENSG00000100888 ENSG00000100888 HGNC:20153 CHKA gene CHKA Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Abnormal muscle tone;Global developmental delay;Intellectual disability;Seizures;Microcephaly;Abnormality of movement;Abnormality of nervous system morphology;Short stature 35202461 False 3 100;0;0 30.556 False ENSG00000110721 ENSG00000110721 HGNC:1937 CHKB gene CHKB Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy, congenital, megaconial type, 602541 21665002;26067811;30986505 False 3 0;0;0 30.556 False ENSG00000100288 ENSG00000100288 HGNC:1938 CHKB gene CHKB London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Choline kinase deficiency (Disorders of complex lipid synthesis);Muscular dystrophy, congenital, megaconial type, 602541 27604308 False 3 50;0;50 30.556 False ENSG00000100288 ENSG00000100288 HGNC:1938 CHMP1A gene CHMP1A Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pontocerebellar hypoplasia, type 8 614961 23023333 False 3 33;67;0 30.556 False ENSG00000131165 ENSG00000131165 HGNC:8740 CHST14 gene CHST14 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ehlers-Danlos syndrome, musculocontractural type 1 601776;CHST14-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) 27604308 False 3 0;0;0 30.556 False ENSG00000169105 ENSG00000169105 HGNC:24464 CHST3 gene CHST3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spondyloepiphyseal dysplasia with congenital joint dislocations 143095;CHST3-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) 20830804 False 3 0;0;0 30.556 False ENSG00000122863 ENSG00000122863 HGNC:1971 CHST6 gene CHST6 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal CHST6-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies);Macular corneal dystrophy 217800 27604308 False 3 0;0;0 30.556 False ENSG00000183196 ENSG00000183196 HGNC:6938 CHSY1 gene CHSY1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Temtamy preaxial brachydactyly syndrome 605282;CHSY1-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) 24269551;21129727 False 3 0;0;0 30.556 False ENSG00000131873 ENSG00000131873 HGNC:17198 CIAO1 gene CIAO1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 10, OMIM:620960 38950322 False 3 100;0;0 30.556 False ENSG00000144021 ENSG00000144021 HGNC:14280 CIC gene CIC Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Mental retardation, autosomal dominant 45 617600 21076407; 28288114; 24896178 False 3 33;0;67 30.556 False ENSG00000079432 ENSG00000079432 HGNC:14214 CIC gene CIC Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Mental retardation, autosomal dominant 45 617600 28288114;24896178;21076407 False 3 0;0;0 30.556 False ENSG00000079432 ENSG00000079432 HGNC:14214 CISD2 gene CISD2 Expert Review Green;NHS GMS;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Wolfram syndrome 2 604928 27604308;17846994;25056293;25371195;29237418 False 3 0;0;100 30.556 False ENSG00000145354 ENSG00000145354 HGNC:24212 CIT gene CIT Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly 17, primary, autosomal recessive, 617090 False 3 100;0;0 30.556 False ENSG00000122966 ENSG00000122966 HGNC:1985 CKAP2L gene CKAP2L Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal FILIPPI SYNDROME. SYNDACTYLY, TYPE I, WITH MICROCEPHALY AND MENTAL RETARDATION 0 False 3 100;0;0 30.556 False ENSG00000169607 ENSG00000169607 HGNC:26877 CLCN2 gene CLCN2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukoencephalopathy with ataxia, OMIM:615651 25655951 False 3 0;0;0 30.556 False ENSG00000114859 ENSG00000114859 HGNC:2020 CLCN3 gene CLCN3 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Neurodevelopmental disorder with hypotonia and brain abnormalities, OMIM:619512;Neurodevelopmental disorder with seizures and brain abnormalities, OMIM:619517 34186028 False 3 100;0;0 30.556 False Other ENSG00000109572 ENSG00000109572 HGNC:2021 CLCN4 gene CLCN4 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Raynaud-Claes syndrome, OMIM:300114 25644381 False 3 0;0;100 30.556 False ENSG00000073464 ENSG00000073464 HGNC:2022 CLCN6 gene CLCN6 NHS GMS;Expert Review Green;Other Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodegeneration, childhood-onset, hypotonia, respiratory insufficiency and brain imaging abnormalities OMIM:619173 29667327;26658788;25794116;21107136;33217309;16950870 False 3 100;0;0 30.556 False ENSG00000011021 ENSG00000011021 HGNC:2024 CLDN11 gene CLDN11 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Leukodystrophy, hypomyelinating, 22, OMIM:619328 33313762 False 3 100;0;0 30.556 False ENSG00000013297 ENSG00000013297 HGNC:8514 CLDN11 gene CLDN11 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Leukodystrophy, hypomyelinating, 22, OMIM:619328 33313762 False 3 100;0;0 30.556 False ENSG00000013297 ENSG00000013297 HGNC:8514 CLDN16 gene CLDN16 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypomagnesemia 3, renal, OMIM:248250 27604308 False 3 0;0;0 30.556 False ENSG00000113946 ENSG00000113946 HGNC:2037 CLDN19 gene CLDN19 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypomagnesemia 5, renal, with ocular involvement 248190 27604308;22422540;17033971 False 3 0;0;0 30.556 False ENSG00000164007 ENSG00000164007 HGNC:2040 CLDN5 gene CLDN5 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted intellectual disability, MONDO:0001071 36477332 False 3 100;0;0 30.556 False ENSG00000184113 ENSG00000184113 HGNC:2047 CLDN5 gene CLDN5 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Brain calcifications 36477332 False 3 100;0;0 30.556 False ENSG00000184113 ENSG00000184113 HGNC:2047 CLEC16A gene CLEC16A Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal severe neurodevelopmental disorder including microcephaly, brain atrophy, corpus callosum dysgenesis, and growth retardation 36538041;37175930 False 3 100;0;0 30.556 False ENSG00000038532 ENSG00000038532 HGNC:29013 CLN3 gene CLN3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ceroid lipofuscinosis, neuronal, 3, 204200 False 3 0;0;0 30.556 False ENSG00000188603 ENSG00000188603 HGNC:2074 CLN3 gene CLN3 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ceroid lipofuscinosis, neuronal, 3, 204200;NEURONAL CEROID LIPOFUSCINOSIS TYPE 3 (CLN3) False 3 100;0;0 30.556 False ENSG00000188603 ENSG00000188603 HGNC:2074 CLN5 gene CLN5 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ceroid lipofuscinosis, neuronal, 5 OMIM:256731;neuronal ceroid lipofuscinosis 5 MONDO:0009745 False 3 100;0;0 30.556 False ENSG00000102805 ENSG00000102805 HGNC:2076 CLN5 gene CLN5 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ceroid lipofuscinosis, neuronal, 5 OMIM:256731;neuronal ceroid lipofuscinosis 5 MONDO:0009745 False 3 0;0;0 30.556 False ENSG00000102805 ENSG00000102805 HGNC:2076 CLN6 gene CLN6 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ceroid lipofuscinosis, neuronal, 6, 601780Ceroid lipofuscinosis, neuronal, Kufs type, adult onset, 204300;CEROID LIPOFUSCINOSIS, NEURONAL, 6 False 3 100;0;0 30.556 False ENSG00000128973 ENSG00000128973 HGNC:2077 CLN6 gene CLN6 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ceroid lipofuscinosis, neuronal, 6, 601780;Ceroid lipofuscinosis, neuronal, Kufs type, adult onset, 204300 False 3 0;0;0 30.556 False ENSG00000128973 ENSG00000128973 HGNC:2077 CLN8 gene CLN8 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ceroid lipofuscinosis, neuronal, 8 False 3 0;0;0 30.556 False ENSG00000182372 ENSG00000182372 HGNC:2079 CLN8 gene CLN8 Expert Review Green;Radboud University Medical Center, Nijmegen;UKGTN Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ceroid lipofuscinosis, neuronal, 8, 600143Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, 610003;NEURONAL CEROID LIPOFUSCINOSIS TYPE 8 (CLN8) False 3 100;0;0 30.556 False ENSG00000182372 ENSG00000182372 HGNC:2079 CLP1 gene CLP1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pontocerebellar hypoplasia 10 OMIM:615803;Pontocerebellar hypoplasia type 10 MONDO:0014349 24766809 False 3 0;100;0 30.556 False ENSG00000172409 ENSG00000172409 HGNC:16999 CLPB gene CLPB NHS GMS;Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal 3-methylglutaconic aciduria, type VIIB, autosomal recessive, OMIM:616271;3-methylglutaconic aciduria, type VIIA, autosomal dominant, OMIM:619835;Neutropenia, severe congenital, 9, autosomal dominant, OMIM:619813 25597510;25597511;25650066;25595726;26916670;28687938;34140661 False 3 33;67;0 30.556 False ENSG00000162129 ENSG00000162129 HGNC:30664 CLPB gene CLPB NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal 3-methylglutaconic aciduria, type VIIB, autosomal recessive, OMIM:616271;3-methylglutaconic aciduria, type VIIA, autosomal dominant, OMIM: 619835;Neutropenia, severe congenital, 9, autosomal dominant, OMIM: 619813 25597510;25597511;25650066;25595726;26916670;28687938;34140661 False 3 100;0;0 30.556 False ENSG00000162129 ENSG00000162129 HGNC:30664 CLPB gene CLPB NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal 3-methylglutaconic aciduria, type VIIB, autosomal recessive, OMIM:616271;3-methylglutaconic aciduria, type VIIA, autosomal dominant, OMIM: 619835;Neutropenia, severe congenital, 9, autosomal dominant, OMIM: 619813 25597510;25597511;25650066;26916670;28687938;34140661 False 3 100;0;0 30.556 True ENSG00000162129 ENSG00000162129 HGNC:30664 CLPP gene CLPP Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Perrault syndrome 3, 614129 False 3 100;0;0 30.556 True ENSG00000125656 ENSG00000125656 HGNC:2084 CLPP gene CLPP Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Perrault syndrome 3, OMIM:614129 27899912;23541340;25956234;26970254;27087618;27650058 False 3 100;0;0 30.556 False ENSG00000125656 ENSG00000125656 HGNC:2084 CLPP gene CLPP Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Perrault syndrome 3, 614129 False 3 100;0;0 30.556 False ENSG00000125656 ENSG00000125656 HGNC:2084 CLTC gene CLTC Other;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Mental retardation, autosomal dominant 56, OMIM:617854 26822784;29100083 False 3 0;0;0 30.556 False ENSG00000141367 ENSG00000141367 HGNC:2092 CMPK2 gene CMPK2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Basal ganglia calcification, idiopathic, 10, autosomal recessive, OMIM:621018;basal ganglia calcification, idiopathic, 10, autosomal recessive, MONDO:0975875 33340416;36443312 False 3 100;0;0 30.556 False ENSG00000134326 ENSG00000134326 HGNC:27015 CMPK2 gene CMPK2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial UMP-CMP kinase 2 deficiency;Developmental delay;Failure to thrive 33340416;36443312 False 3 100;0;0 30.556 False ENSG00000134326 ENSG00000134326 HGNC:27015 CMPK2 gene CMPK2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Basal ganglia calcification, idiopathic, 10, autosomal recessive, OMIM:621018;basal ganglia calcification, idiopathic, 10, autosomal recessive, MONDO:0975875 33340416;36443312 False 3 100;0;0 30.556 False ENSG00000134326 ENSG00000134326 HGNC:27015 CNKSR2 gene CNKSR2 Victorian Clinical Genetics Services;Expert Review Green;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Intellectual developmental disorder, X-linked, syndromic, Houge type, OMIM:301008;intellectual disability, X-linked, syndromic, Houge type, MONDO:0030909 28098945;25223753;22511892;25644381;28098945;34266427 False 3 100;0;0 30.556 False ENSG00000149970 ENSG00000149970 HGNC:19701 CNNM2 gene CNNM2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Hypomagnesaemia type 6, renal (Disorder of magnesium metabolism);Hypomagnesemia 6, renal 613882;Hypomagnesemia, seizures, and mental retardation 616418 27604308 False 3 100;0;0 30.556 False ENSG00000148842 ENSG00000148842 HGNC:103 CNNM2 gene CNNM2 Radboud University Medical Center, Nijmegen;UKGTN;Illumina TruGenome Clinical Sequencing Services;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Hypomagnesemia, seizures, and mental retardation, OMIM:616418;Hypomagnesemia, seizures, and mental retardation, MONDO:0014631 21397062; 24699222; 27604308 False 3 100;0;0 30.556 False ENSG00000148842 ENSG00000148842 HGNC:103 CNOT1 gene CNOT1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Holoprosencephaly 12, with or without pancreatic agenesis, 618500;global developmental delay 31006510;21679367;31006513 False 3 0;0;0 30.556 False ENSG00000125107 ENSG00000125107 HGNC:7877 CNOT2 gene CNOT2 Expert Review Green;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies, 618608 31512373;31145527;28135719;28159701;30768759;21505450;18076123;22247066 False 3 100;0;0 30.556 False ENSG00000111596 ENSG00000111596 HGNC:7878 CNOT3 gene CNOT3 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown CNOT3 syndrome;intellectual disability, global developmental delay;Intellectual developmental disorder with speech delay, autism, and dysmorphic facies, 618672 25529582;28135719;28135719;31201375;24121232 False 3 100;0;0 30.556 False ENSG00000088038 ENSG00000088038 HGNC:7879 CNOT9 gene CNOT9 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted intellectual disability, MONDO:0001071 37092538 False 3 100;0;0 30.556 False ENSG00000144580 ENSG00000144580 HGNC:10445 CNTNAP1 gene CNTNAP1 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypomyelinating neuropathy, congenital, 3 618186;Lethal congenital contracture syndrome 7 616286 28374019;29511323;27668699 False 3 100;0;0 30.556 False ENSG00000108797 ENSG00000108797 HGNC:8011 CNTNAP1 gene CNTNAP1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypomyelinating neuropathy, congenital, 3, OMIM:618186 28374019;29511323;29882456 False 3 100;0;0 30.556 False ENSG00000108797 ENSG00000108797 HGNC:8011 CNTNAP2 gene CNTNAP2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cortical dysplasia-focal epilepsy syndrome, 610042{Autism susceptibility 15}, 612100Pitt-Hopkins like syndrome 1, 610042;CORTICAL DYSPLASIA-FOCAL EPILEPSY SYNDROME (CDFES) False 3 100;0;0 30.556 False ENSG00000174469 ENSG00000174469 HGNC:13830 COA6 gene COA6 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 13, OMIM:616501 False 3 100;0;0 30.556 False ENSG00000168275 ENSG00000168275 HGNC:18025 COA6 gene COA6 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 13, OMIM:616501 22277967;24549041;25959673;25339201 False 3 100;0;0 30.556 False ENSG00000168275 ENSG00000168275 HGNC:18025 COA7 gene COA7 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 OMIM:618387;spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MONDO:0020770 27683825;29718187;30885959 False 3 100;0;0 30.556 False ENSG00000162377 ENSG00000162377 HGNC:25716 COA7 gene COA7 Expert Review Green;Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 OMIM:618387;spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MONDO:0020770 27683825;29718187 False 3 0;0;0 30.556 False ENSG00000162377 ENSG00000162377 HGNC:25716 COA7 gene COA7 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 OMIM:618387;spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MONDO:0020770 29718187;27683825 False 3 0;0;0 30.556 False ENSG00000162377 ENSG00000162377 HGNC:25716 COASY gene COASY Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodegeneration with brain iron accumulation 6, OMIM:615643;neurodegeneration with brain iron accumulation 6, MONDO:0014290;Pontocerebellar hypoplasia, type 12, OMIM:618266;pontocerebellar hypoplasia, type 12, MONDO:0032643 11980892;25778941;24360804;27021474;28489334;30089828;36495139 False 3 33;67;0 30.556 False ENSG00000068120 ENSG00000068120 HGNC:29932 COG1 gene COG1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIg, 611209;COG1-CDG (CDG-IIG) False 3 100;0;0 30.556 False ENSG00000166685 ENSG00000166685 HGNC:6545 COG1 gene COG1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Component of COG complex 1 deficiency (Disorders of multiple glycosylation and other glycosylation pathways, conserved oligomeric Golgi (COG) complex deficiency);Congenital disorder of glycosylation, type IIg 611209 27604308 False 3 0;0;0 30.556 False ENSG00000166685 ENSG00000166685 HGNC:6545 COG4 gene COG4 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIj, 613489;COG4-CDG (CDG-IIJ) 19494034;21185756 False 3 60;40;0 30.556 False ENSG00000103051 ENSG00000103051 HGNC:18620 COG4 gene COG4 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Component of COG complex 4 deficiency (Disorders of multiple glycosylation and other glycosylation pathways, conserved oligomeric Golgi (COG) complex deficiency);Congenital disorder of glycosylation, type IIj 613489 19651599;21185756;19494034;11980916 False 3 0;0;0 30.556 False ENSG00000103051 ENSG00000103051 HGNC:18620 COG5 gene COG5 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIi 613612;Component of COG complex 5 deficiency (Disorders of multiple glycosylation and other glycosylation pathways, conserved oligomeric Golgi (COG) complex deficiency) 27604308 False 3 0;0;0 30.556 False ENSG00000164597 ENSG00000164597 HGNC:14857 COG5 gene COG5 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type III, 613612;COG5-CDG;CDG-III 19690088;23430875;23228021;28960046 False 3 0;100;0 30.556 False ENSG00000164597 ENSG00000164597 HGNC:14857 COG6 gene COG6 Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIl, 614576;Shaheen syndrome, 615328 26260076;20605848;23430903;23606727;28139241;28742265;29445937;29709711 False 3 100;0;0 30.556 False ENSG00000133103 ENSG00000133103 HGNC:18621 COG6 gene COG6 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Component of COG complex 6 deficiency (Disorders of multiple glycosylation and other glycosylation pathways, conserved oligomeric Golgi (COG) complex deficiency);Shaheen syndrome 615328;Congenital disorder of glycosylation, type IIl 614576 26260076;11980916 False 3 0;0;0 30.556 False ENSG00000133103 ENSG00000133103 HGNC:18621 COG7 gene COG7 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Component of COG complex 7 deficiency (Disorders of multiple glycosylation and other glycosylation pathways, conserved oligomeric Golgi (COG) complex deficiency);Congenital disorder of glycosylation, type IIe 608779 27604308 False 3 0;0;0 30.556 False ENSG00000168434 ENSG00000168434 HGNC:18622 COG7 gene COG7 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIe, 608779;COG7-CDG (CDG-IIE) False 3 100;0;0 30.556 False ENSG00000168434 ENSG00000168434 HGNC:18622 COG8 gene COG8 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIh 611182;Component of COG complex 8 deficiency (Disorders of multiple glycosylation and other glycosylation pathways, conserved oligomeric Golgi (COG) complex deficiency) 17220172;17331980;11980916 False 3 0;0;0 30.556 False ENSG00000213380 ENSG00000213380 HGNC:18623 COG8 gene COG8 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIh, 611182;COG8-CDG (CDG-IIH) False 3 100;0;0 30.556 False ENSG00000213380 ENSG00000213380 HGNC:18623 COL4A1 gene COL4A1 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Variable phenotype - porencephaly, destructive cerebral lesions, eye anomalies, intracerebral calcification;Porencephaly 1 MIM#607595 False 3 0;0;0 30.556 False ENSG00000187498 ENSG00000187498 HGNC:2202 COL4A1 gene COL4A1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Porencephaly 1, 175780Brain small vessel disease with hemorrhage, 607595Angiopathy, hereditary, with nephropathy, aneurysms, and muscle, 611773Brain small vessel disease with Axenfeld-Rieger anomaly, 607595{Hemorrhage, intracerebral, susceptibility to}, 614519;PORENCEPHALY 1 False 3 100;0;0 30.556 False ENSG00000187498 ENSG00000187498 HGNC:2202 COL4A2 gene COL4A2 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Porencephaly 2, 614483{Hemorrhage, intracerebral, susceptibility to}, 614519;PORENCEPHALY 2 False 3 100;0;0 30.556 False ENSG00000134871 ENSG00000134871 HGNC:2203 COL4A3BP gene COL4A3BP Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual developmental disorder, autosomal dominant 34, OMIM:616351 25533962;33347465;34688657;36976648;37892645 False 3 100;0;0 30.556 False ENSG00000113163 ENSG00000113163 HGNC:2205 COLEC11 gene COLEC11 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3MC syndrome 2, 265050;3MC SYNDROME 2 False 3 100;0;0 30.556 False ENSG00000118004 ENSG00000118004 HGNC:17213 COLGALT1 gene COLGALT1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Brain small vessel disease 3, OMIM:618360 30412317;33709034;31759980 False 3 100;0;0 30.556 False ENSG00000130309 ENSG00000130309 HGNC:26182 COPB2 gene COPB2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted osteoporosis;developmental delay 34450031 False 3 100;0;0 30.556 False ENSG00000184432 ENSG00000184432 HGNC:2232 COQ2 gene COQ2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Coenzyme Q10 deficiency, primary, 1, OMIM:607426 False 3 100;0;0 30.556 True ENSG00000173085 ENSG00000173085 HGNC:25223 COQ2 gene COQ2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal General Leukodystrophy & Mitochondrial Leukoencephalopathy;Coenzyme Q10 deficiency, primary, 1, OMIM:607426 25655951 False 3 0;0;0 30.556 False ENSG00000173085 ENSG00000173085 HGNC:25223 COQ2 gene COQ2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Coenzyme Q10 deficiency, primary, 1, OMIM:607426 27604308 False 3 100;0;0 30.556 False ENSG00000173085 ENSG00000173085 HGNC:25223 COQ4 gene COQ4 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Coenzyme Q10 deficiency, primary, 7, OMIM:616276 27604308 False 3 100;0;0 30.556 False ENSG00000167113 ENSG00000167113 HGNC:19693 COQ4 gene COQ4 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal COENZYME Q10 DEFICIENCY, PRIMARY, 7 25658047 False 3 0;100;0 30.556 False ENSG00000167113 ENSG00000167113 HGNC:19693 COQ4 gene COQ4 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Coenzyme Q10 deficiency, primary, 7, OMIM:616276 False 3 100;0;0 30.556 True ENSG00000167113 ENSG00000167113 HGNC:19693 COQ6 gene COQ6 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Steroid-resistant nephrotic syndrome;Disorders of ubiquinone metabolism and biosynthesis;Coenzyme Q10 deficiency, primary, 6, 614650 PMID: 21540551 False 3 100;0;0 30.556 True ENSG00000119723 ENSG00000119723 HGNC:20233 COQ6 gene COQ6 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Coenzyme Q10 deficiency, primary, 6, 614650;Steroid-resistant nephrotic syndrome;Disorders of CoQ10 biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Disorders of ubiquinone metabolism and biosynthesis 27604308 False 3 100;0;0 30.556 False ENSG00000119723 ENSG00000119723 HGNC:20233 COQ7 gene COQ7 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal "?Coenzyme Q10 deficiency, primary, 8 616733" 26084283;28409910 False 3 50;50;0 30.556 False ENSG00000167186 ENSG00000167186 HGNC:2244 COQ7 gene COQ7 Expert Review Green;NHS GMS;Expert list;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Coenzyme Q10 deficiency, primary, 8 616733;complex multisystem presentation 28409910;26084283;30369941 False 3 50;50;0 30.556 True ENSG00000167186 ENSG00000167186 HGNC:2244 COQ8A gene COQ8A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of ubiquinone metabolism and biosynthesis;Coenzyme Q10 deficiency, primary, 4, 612016;Coenzyme Q10 deficiency False 3 100;0;0 30.556 True ENSG00000163050 ENSG00000163050 HGNC:16812 COQ8A gene COQ8A Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Coenzyme Q10 deficiency, primary 4, 612016;Spinocerebellar Ataxia Type 25655951 False 3 0;0;0 30.556 False ENSG00000163050 ENSG00000163050 HGNC:16812 COQ8A gene COQ8A London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Coenzyme Q10 deficiency;Disorders of CoQ10 biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Disorders of ubiquinone metabolism and biosynthesis;Coenzyme Q10 deficiency, primary, 4, 612016 27604308 False 3 100;0;0 30.556 False ENSG00000163050 ENSG00000163050 HGNC:16812 COQ8A gene COQ8A Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Coenzyme Q10 deficiency, primary, 4, 612016;COENZYME Q10 DEFICIENCY 25529582;24896178 False 3 100;0;0 30.556 False ENSG00000163050 ENSG00000163050 HGNC:16812 COQ8B gene COQ8B Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Nephrotic syndrome, type 9 24270420 False 3 100;0;0 30.556 False ENSG00000123815 ENSG00000123815 HGNC:19041 COQ8B gene COQ8B Victorian Clinical Genetics Services;Expert Review Green;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Nephrotic syndrome, type 9 PMID: 24270420 (8 unrelated families). False 3 100;0;0 30.556 True ENSG00000123815 ENSG00000123815 HGNC:19041 COQ9 gene COQ9 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of ubiquinone metabolism and biosynthesis;Coenzyme Q10 deficiency, primary, 5, 614654;Coenzyme Q10 deficiency False 3 50;50;0 30.556 True ENSG00000088682 ENSG00000088682 HGNC:25302 COQ9 gene COQ9 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Coenzyme Q10 deficiency, primary, 5, 614654;Coenzyme Q10 deficiency;Disorders of CoQ10 biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Disorders of ubiquinone metabolism and biosynthesis 27604308 False 3 50;50;0 30.556 False ENSG00000088682 ENSG00000088682 HGNC:25302 COX10 gene COX10 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046;General Leukodystrophy & Mitochondrial Leukoencephalopathy 24100867;25655951;12928484 False 3 0;0;0 30.556 False ENSG00000006695 ENSG00000006695 HGNC:2260 COX10 gene COX10 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046 11317352;17275378;10746566;15214016;17604671;19107570;22499348;9843204;10647889;15455402;15863660;10944442;20818383;9837813;12928484 False 3 100;0;0 30.556 False ENSG00000006695 ENSG00000006695 HGNC:2260 COX10 gene COX10 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046;Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due to cytochrome coxidase deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000006695 ENSG00000006695 HGNC:2260 COX10 gene COX10 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046 False 3 100;0;0 30.556 False ENSG00000006695 ENSG00000006695 HGNC:2260 COX11 gene COX11 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 23, OMIM:620275;Mitochondrial complex IV deficiency, nuclear type 23, MONDO:0859520 36030551;38068960 False 3 50;0;50 30.556 False ENSG00000166260 ENSG00000166260 HGNC:2261 COX11 gene COX11 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 23, OMIM:620275;Mitochondrial complex IV deficiency, nuclear type 23, MONDO:0859520 36030551;38068960 False 3 50;0;50 30.556 False ENSG00000166260 ENSG00000166260 HGNC:2261 COX11 gene COX11 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 23, OMIM:620275;Mitochondrial complex IV deficiency, nuclear type 23, MONDO:0859520 36030551;38068960 False 3 67;0;33 30.556 False ENSG00000166260 ENSG00000166260 HGNC:2261 COX14 gene COX14 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, 220110;Isolated complex IV deficiency;Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors) 27604308 False 3 100;0;0 30.556 False ENSG00000178449 ENSG00000178449 HGNC:28216 COX15 gene COX15 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119;Mitochondrial Leukoencephalopathy 25655951 False 3 0;0;0 30.556 False ENSG00000014919 ENSG00000014919 HGNC:2263 COX15 gene COX15 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119 27604308 False 3 100;0;0 30.556 False ENSG00000014919 ENSG00000014919 HGNC:2263 COX15 gene COX15 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119 False 3 100;0;0 30.556 False ENSG00000014919 ENSG00000014919 HGNC:2263 COX15 gene COX15 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119 False 3 100;0;0 30.556 False ENSG00000014919 ENSG00000014919 HGNC:2263 COX18 gene COX18 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal mitochondrial disease, MONDO:0044970;Charcot-Marie-Tooth disease, MONDO:0015626 37468577;40830826 False 3 50;25;25 30.556 False ENSG00000163626 ENSG00000163626 HGNC:26801 COX18 gene COX18 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal mitochondrial disease, MONDO:0044970;Charcot-Marie-Tooth disease, MONDO:0015626 37468577;40830826 False 3 33;33;33 30.556 False ENSG00000163626 ENSG00000163626 HGNC:26801 COX20 gene COX20 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex IV deficiency;Mitochondrial complex IV deficiency, 220110 False 3 100;0;0 30.556 True ENSG00000203667 ENSG00000203667 HGNC:26970 COX20 gene COX20 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, 220110;Isolated complex IV deficiency;Complex IV Mitochondrial respiratory chain disorders caused by nuclear variants only;OXPHOS assembly factors 27604308 False 3 100;0;0 30.556 False ENSG00000203667 ENSG00000203667 HGNC:26970 COX4I1 gene COX4I1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 16, OMIM:619060 28766551;31290619;33578848 False 3 50;50;0 30.556 False ENSG00000131143 ENSG00000131143 HGNC:2265 COX4I1 gene COX4I1 Expert Review Green;NHS GMS;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 16, OMIM:619060 28766551;31290619;33578848 False 3 67;33;0 30.556 True ENSG00000131143 ENSG00000131143 HGNC:2265 COX5A gene COX5A Expert Review Green;NHS GMS;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Mitochondrial complex IV deficiency, nuclear type 20, OMIM:619064;Mitochondrial complex IV deficiency, nuclear type 23, MONDO:0859520 28247525;35246835 False 3 50;50;0 30.556 True ENSG00000178741 ENSG00000178741 HGNC:2267 COX5A gene COX5A NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Mitochondrial complex IV deficiency, nuclear type 20, OMIM:619064;Mitochondrial complex IV deficiency, nuclear type 23, MONDO:0859520 28247525;35246835 False 3 50;50;0 30.556 False ENSG00000178741 ENSG00000178741 HGNC:2267 COX6A1 gene COX6A1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Charcot-Marie-Tooth disease, recessive intermediate D, 616039 False 3 100;0;0 30.556 False ENSG00000111775 ENSG00000111775 HGNC:2277 COX6A1 gene COX6A1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Charcot-Marie-Tooth disease, recessive intermediate D, 616039 False 3 100;0;0 30.556 True ENSG00000111775 ENSG00000111775 HGNC:2277 COX6A2 gene COX6A2 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 18, OMIM:619062 23460811;31155743;32744742 False 3 67;33;0 30.556 False ENSG00000156885 ENSG00000156885 HGNC:2279 COX6A2 gene COX6A2 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 18, OMIM:619062 23460811;31155743;32744742 False 3 67;33;0 30.556 False ENSG00000156885 ENSG00000156885 HGNC:2279 COX6B1 gene COX6B1 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 7, OMIM:619051 18499082;24781756 False 3 100;0;0 30.556 False ENSG00000126267 ENSG00000126267 HGNC:2280 COX6B1 gene COX6B1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 7, OMIM:619051 18499082;24781756 False 3 100;0;0 30.556 False ENSG00000126267 ENSG00000126267 HGNC:2280 COX7B gene COX7B London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Isolated complex IV deficiency;Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits);Linear skin defects with multiple congenital anomalies;Aplasia cutis congenita, reticulolinear, with microcephaly, facial dysmorphism and other congenital anomalies, 300887;MICROPHTHALMIA WITH LINEAR SKIN LESIONS 27604308 False 3 100;0;0 30.556 False ENSG00000131174 ENSG00000131174 HGNC:2291 COX7B gene COX7B Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Isolated complex IV deficiency;Aplasia cutis congenita, reticulolinear, with microcephaly, facial dysmorphism and other congenital anomalies, 300887;MICROPHTHALMIA WITH LINEAR SKIN LESIONS;Linear skin defects with multiple congenital anomalies False 3 100;0;0 30.556 True ENSG00000131174 ENSG00000131174 HGNC:2291 CP gene CP London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cerebellar ataxia, 604290;Hemosiderosis, systemic, due to aceruloplasminemia, 604290 False 3 0;0;0 30.556 False ENSG00000047457 ENSG00000047457 HGNC:2295 CPE gene CPE Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder and hypogonadotropic hypogonadism, OMIM:619326 26120850;32936766;34383079 False 3 67;33;0 30.556 False ENSG00000109472 ENSG00000109472 HGNC:2303 CPLX1 gene CPLX1 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental and epileptic encephalopathy 63, OMIM:617976;developmental and epileptic encephalopathy, 63, MONDO:0033372 26539891;28422131 False 3 100;0;0 30.556 False ENSG00000168993 ENSG00000168993 HGNC:2309 CPOX gene CPOX London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Coproporphyria, OMIM:121300;Harderoporphyria, OMIM:618892 6886003;7757079;8012360;9454777;10505225;11074238;11309681;16159891;21103937;23236641;23605133;30828546;33008663;37540847;38940544;40296768 False 3 100;0;0 30.556 False ENSG00000080819 ENSG00000080819 HGNC:2321 CPS1 gene CPS1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Carbamoylphosphate synthetase I deficiency;Carbamoylphosphate synthetase I deficiency (Urea cycle disorders and inherited hyperammonaemias) 27604308;24816252 False 3 0;0;0 30.556 False ENSG00000021826 ENSG00000021826 HGNC:2323 CPS1 gene CPS1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Carbamoylphosphate synthetase I deficiency, 237300{Pulmonary hypertension, neonatal, susceptibility to}, 615371{Venoocclusive disease after bone marrow transplantation};CARBAMOYL PHOSPHATE SYNTHETASE 1 DEFICIENCY (CPS1D) False 3 100;0;0 30.556 False ENSG00000021826 ENSG00000021826 HGNC:2323 CPT1A gene CPT1A NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Carnitine palmitoyltransferase I (CPTI) deficiency (Disorders of carnitine transport and the carnitine cycle);CPT deficiency, hepatic, type IA 27604308 False 3 0;0;100 30.556 False ENSG00000110090 ENSG00000110090 HGNC:2328 CPT2 gene CPT2 NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal CPT II deficiency, infantile, OMIM:600649;CPT II deficiency, lethal neonatal, OMIM:608836;CPT II deficiency, myopathic, stress-induced, OMIM:255110;Carnitine palmitoyltransferase II (CPTII) deficiency (Disorders of carnitine transport and the carnitine cycle) 23911907;10873395;11994355;15622536;21913903;23184072;24843804 False 3 50;0;50 30.556 False ENSG00000157184 ENSG00000157184 HGNC:2330 CRADD gene CRADD Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mental retardation, autosomal recessive 34, with variant lissencephaly, OMIM:614499 22279524;27773430;30914828 False 3 33;0;67 30.556 False ENSG00000169372 ENSG00000169372 HGNC:2340 CRB2 gene CRB2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal VENTRICULOMEGALY WITH CYSTIC KIDNEY DISEASE 25557780 False 3 33;67;0 30.556 False ENSG00000148204 ENSG00000148204 HGNC:18688 CREB3L3 gene CREB3L3 Expert Review Green;NHS GMS;South West GLH Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Hypertriglyceridemia 2, OMIM:619324;Hypertriglyceridemia (disease) MONDO:0005347 29954705;21666694;26427795;22135386 False 3 100;0;0 30.556 False ENSG00000060566 ENSG00000060566 HGNC:18855 CREBBP gene CREBBP Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Rubinstein-Taybi syndrome, 180849;RUBINSTEIN-TAYBI SYNDROME TYPE 1 (RSTS1) False 3 100;0;0 30.556 False ENSG00000005339 ENSG00000005339 HGNC:2348 CRELD1 gene CRELD1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Jeffries-Lakhani neurodevelopmental syndrome, OMIM:620771 37947183;39313616 False 3 100;0;0 30.556 False ENSG00000163703 ENSG00000163703 HGNC:14630 CRLS1 gene CRLS1 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 57, OMIM:620167 35147173 False 3 100;0;0 30.556 False ENSG00000088766 ENSG00000088766 HGNC:16148 CRLS1 gene CRLS1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 57, OMIM:620167 35147173 False 3 100;0;0 30.556 False ENSG00000088766 ENSG00000088766 HGNC:16148 CRNKL1 gene CRNKL1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Microcephaly, progressive, with simplified gyral pattern and cerebellar hypoplasia, OMIM:621436;complex neurodevelopmental disorder, MONDO:0100038 40857589 False 3 100;0;0 30.556 False ENSG00000101343 ENSG00000101343 HGNC:15762 CSDE1 gene CSDE1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Autism;Global developmental delay;Intellectual disability 31579823 False 3 100;0;0 30.556 False ENSG00000009307 ENSG00000009307 HGNC:29905 CSF1R gene CSF1R NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Leukoencephalopathy, diffuse hereditary, with spheroids, OMIM:221820;Brain abnormalities, neurodegeneration, and dysosteosclerosis, OMIM:618476 22197934;24336230;23408870;30982609;30982608 False 3 100;0;0 30.556 False ENSG00000182578 ENSG00000182578 HGNC:2433 CSGALNACT1 gene CSGALNACT1 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation;Skeletal dysplasia, mild, with joint laxity and advanced bone age OMIM:618870;skeletal dysplasia, mild, with joint laxity and advanced bone age MONDO:0030029 31705726;31325655;31705726 False 3 100;0;0 30.556 False ENSG00000147408 ENSG00000147408 HGNC:24290 CSNK1G1 gene CSNK1G1 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown severe non-syndromic early-onset epilepsy;Global developmental delay;Intellectual disability;Autism;Seizures;Abnormality of the face;Abnormality of limbs 24463883;33009664 False 3 0;25;75 30.556 False ENSG00000169118 ENSG00000169118 HGNC:2454 CSNK2A1 gene CSNK2A1 Victorian Clinical Genetics Services;Expert Review Green;Other Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Okur-Chung neurodevelopmental syndrome, OMIM:617062 PubMed: 27048600 False 3 100;0;0 30.556 False ENSG00000101266 ENSG00000101266 HGNC:2457 CSNK2B gene CSNK2B Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Poirier-Bienvenu neurodevelopmental syndrome, OMIM:618732;Poirier-Bienvenu neurodevelopmental syndrome, MONDO:0032889 28762608;28585349;27094248;30655572 False 3 100;0;0 30.556 False ENSG00000204435 ENSG00000204435 HGNC:2460 CSPP1 gene CSPP1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal JOUBERT SYNDROME WITH OR WITHOUT JEUNE ASPHYXIATING THORACIC DYSTROPHY 24360808 False 3 33;67;0 30.556 False ENSG00000104218 ENSG00000104218 HGNC:26193 CSTB gene CSTB Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800 9012407;15329070;9342192;8596935 False 3 33;67;0 30.556 False Other - please provide details in the comments ENSG00000160213 ENSG00000160213 HGNC:2482 CTBP1 gene CTBP1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome, 617915 27094857;28955726;31041561 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000159692 ENSG00000159692 HGNC:2494 CTC1 gene CTC1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Coats Plus syndrome;Cerebroretinal microangiopathy with calcifications and cysts, 612199 22387016;22267198 False 3 0;0;0 30.556 False ENSG00000178971 ENSG00000178971 HGNC:26169 CTCF gene CTCF Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted INTELLECTUAL DISABILITY 23746550 False 3 100;0;0 30.556 False ENSG00000102974 ENSG00000102974 HGNC:13723 CTDP1 gene CTDP1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital cataracts, facial dysmorphism, and neuropathy, 604168;CONGENITAL CATARACTS FACIAL DYSMORPHISM AND NEUROPATHY SYNDROME (CCFDN) False 3 100;0;0 30.556 False ENSG00000060069 ENSG00000060069 HGNC:2498 CTH gene CTH London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cystathioninuria, 219500 False 3 0;0;0 30.556 False ENSG00000116761 ENSG00000116761 HGNC:2501 CTNNA2 gene CTNNA2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cortical dysplasia, complex, with other brain malformations 9, OMIM:618174 30013181 False 3 0;100;0 30.556 False ENSG00000066032 ENSG00000066032 HGNC:2510 CTNNB1 gene CTNNB1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with spastic diplegia and visual defects, OMIM:615075 23033978;24614104;25326669;26968164;27915094;34321325 False 3 100;0;0 30.556 False ENSG00000168036 ENSG00000168036 HGNC:2514 CTNND1 gene CTNND1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown developmental delay 32196547 False 3 100;0;0 30.556 False ENSG00000198561 ENSG00000198561 HGNC:2515 CTNS gene CTNS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cystinosis, atypical nephropathic 219750 False 3 0;0;0 30.556 False ENSG00000040531 ENSG00000040531 HGNC:2518 CTR9 gene CTR9 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Macrocephaly, HP:0000256;Motor delay, HP:0001270;intellectual disability, MONDO:0001071;Delayed speech and language development;Behavioral abnormality;Autistic behavior;Failure to thrive;Feeding difficulties;Abnormality of the cardiovascular system 35499524;35717577 False 3 67;33;0 30.556 False ENSG00000198730 ENSG00000198730 HGNC:16850 CTSA gene CTSA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Galactosialidosis 27604308 False 3 0;0;0 30.556 False ENSG00000064601 ENSG00000064601 HGNC:9251 CTSA gene CTSA Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Galactosialidosis, 256540;GALACTOSIALIDOSIS (GSL) False 3 50;50;0 30.556 False ENSG00000064601 ENSG00000064601 HGNC:9251 CTSC gene CTSC Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Haim-Munk syndrome 245010;Papillon-Lefevre syndrome 245000;Periodontitis 1, juvenile 170650 27604308 False 3 0;0;0 30.556 False ENSG00000109861 ENSG00000109861 HGNC:2528 CTSD gene CTSD London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ceroid lipofuscinosis, neuronal, 10, 610127 False 3 0;0;0 30.556 False ENSG00000117984 ENSG00000117984 HGNC:2529 CTSD gene CTSD Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ceroid lipofuscinosis, neuronal, 10, 610127;NEURONAL CEROID LIPOFUSCINOSIS TYPE 10 (CLN10) False 3 100;0;0 30.556 False ENSG00000117984 ENSG00000117984 HGNC:2529 CTSF gene CTSF NHS GMS;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ceroid lipofuscinosis, neuronal, 13, Kufs type OMIM:615362;neuronal ceroid lipofuscinosis 13 MONDO:0014147 23297359;25274848 False 3 100;0;0 30.556 False ENSG00000174080 ENSG00000174080 HGNC:2531 CTSK gene CTSK London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pycnodysostosis 27604308 False 3 0;0;0 30.556 False ENSG00000143387 ENSG00000143387 HGNC:2536 CTU2 gene CTU2 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal DREAM PL syndrome;Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, 618142 27480277;26633546 False 3 100;0;0 30.556 False ENSG00000174177 ENSG00000174177 HGNC:28005 CUBN gene CUBN London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intrinsic factor receptor deficiency due to CUBN mutations (Disorders of cobalamin absorption, transport and metabolism);Megaloblastic anemia-1, Finnish type;Proteinuric renal disease;Unexplained kidney failure in young people False 3 0;0;0 30.556 False ENSG00000107611 ENSG00000107611 HGNC:2548 CUL3 gene CUL3 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with or without autism or seizures, OMIM:619239 32341456;25969726;31696658;33097317;30311385 False 3 100;0;0 30.556 False ENSG00000036257 ENSG00000036257 HGNC:2553 CUL4B gene CUL4B Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory;UKGTN Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked, syndromic 15 (Cabezas type), 300354;MENTAL RETARDATION SYNDROMIC X-LINKED CABEZAS TYPE (MRXC) False 3 100;0;0 30.556 False ENSG00000158290 ENSG00000158290 HGNC:2555 CUX1 gene CUX1 Expert Review;Expert Review Green;Expert Review;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Global developmental delay with or without impaired intellectual development, 618330 25059644;20510857;30014507 False 3 100;0;0 30.556 False ENSG00000257923 ENSG00000257923 HGNC:2557 CUX2 gene CUX2 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental and epileptic encephalopathy 67, OMIM:618141;Seizures;Intellectual disability;Autistic behaviour 21331220;26350204;29630738;29795476;23020937;23934111 False 3 40;0;60 30.556 False ENSG00000111249 ENSG00000111249 HGNC:19347 CWC27 gene CWC27 Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Retinitis pigmentosa with or without skeletal anomalies, 250410 28285769 False 3 100;0;0 30.556 False ENSG00000153015 ENSG00000153015 HGNC:10664 CWF19L1 gene CWF19L1 Expert Review Green;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spinocerebellar ataxia, autosomal recessive 17, 616127;intellectual disability, developmental delay 25361784;15981765;26197978;27016154;30167849 False 3 100;0;0 30.556 False ENSG00000095485 ENSG00000095485 HGNC:25613 CXorf56 gene CXorf56 Expert Review Green;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Intellectual developmental disorder, X-linked 107, OMIM:301013 29374277;31822863 False 3 50;50;0 30.556 False ENSG00000018610 ENSG00000018610 HGNC:26239 CYB5R3 gene CYB5R3 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Methemoglobinemia, type I, 250800Methemoglobinemia, type II, 250800;METHEMOGLOBINEMIA DUE TO DEFICIENCY OF METHEMOGLOBIN REDUCTASE False 3 100;0;0 30.556 False ENSG00000100243 ENSG00000100243 HGNC:2873 CYC1 gene CYC1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 6; MC3DN6 23910460 False 3 33;67;0 30.556 False ENSG00000179091 ENSG00000179091 HGNC:2579 CYC1 gene CYC1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex III deficiency;Mitochondrial complex III deficiency, nuclear type 6, 615453 False 3 100;0;0 30.556 False ENSG00000179091 ENSG00000179091 HGNC:2579 CYC1 gene CYC1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex III deficiency;Mitochondrial complex III deficiency, nuclear type 6, 615453 False 3 100;0;0 30.556 True ENSG00000179091 ENSG00000179091 HGNC:2579 CYCS gene CYCS Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Thrombocytopenia 4, OMIM:612004 18345000;24326104;30051457 False 3 100;0;0 30.556 False ENSG00000172115 ENSG00000172115 HGNC:19986 CYCS gene CYCS Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Thrombocytopenia 4, OMIM:612004 18345000;24326104;30051457 False 3 75;25;0 30.556 False ENSG00000172115 ENSG00000172115 HGNC:19986 CYFIP2 gene CYFIP2 Expert Review;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Epileptic encephalopathy, early infantile, 65, 618008;Epileptic encephalopathy, early infantile 65, 618008 12818175;30664714;20537992;29534297;25432536;27524794;29667327 False 3 100;0;0 30.556 False ENSG00000055163 ENSG00000055163 HGNC:13760 CYP27A1 gene CYP27A1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal General Leukodystrophy & Mitochondrial Leukoencephalopathy;Cerebrotendinous xanthomatosis, 213700 25655951 False 3 0;0;0 30.556 False ENSG00000135929 ENSG00000135929 HGNC:2605 CYP27A1 gene CYP27A1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cerebrotendinous xanthomatosis, 213700 27604308 False 3 0;0;0 30.556 False ENSG00000135929 ENSG00000135929 HGNC:2605 CYP2U1 gene CYP2U1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 56, autosomal recessive False 3 0;0;0 30.556 False ENSG00000155016 ENSG00000155016 HGNC:20582 CYP7B1 gene CYP7B1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Bile acid synthesis defect, congenital, 3 613812;Spastic paraplegia 5A, autosomal recessive 270800 27604308;9802883;18252231;19187859;31337596 False 3 0;0;0 30.556 False ENSG00000172817 ENSG00000172817 HGNC:2652 CYP7B1 gene CYP7B1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 5A, autosomal recessive , OMIM:270800 19187859;19439420;24117163 False 3 67;33;0 30.556 False ENSG00000172817 ENSG00000172817 HGNC:2652 D2HGDH gene D2HGDH NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal D-2-hydroxyglutaric aciduria 27604308 False 3 0;0;100 30.556 False ENSG00000180902 ENSG00000180902 HGNC:28358 D2HGDH gene D2HGDH Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal L2-Hydroxyglutaric aciduria 25655951 False 3 0;0;0 30.556 False ENSG00000180902 ENSG00000180902 HGNC:28358 D2HGDH gene D2HGDH Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal D-2-hydroxyglutaric aciduria, 600721 15609246;16081310 False 3 0;25;75 30.556 False ENSG00000180902 ENSG00000180902 HGNC:28358 DAG1 gene DAG1 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Walker-Warburg syndrome;Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9 613818;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9 616538 21388311;25529582 False 3 50;50;0 30.556 False ENSG00000173402 ENSG00000173402 HGNC:2666 DAGLA gene DAGLA NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted intellectual disability, MONDO:0001071 35737950 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000134780 ENSG00000134780 HGNC:1165 DARS gene DARS Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypomyelination with brainstem and spinal cord involvement and leg spasticity False 3 25;25;50 30.556 False ENSG00000115866 ENSG00000115866 HGNC:2678 DARS gene DARS Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypomyelination with brainstem and spinal cord involvement and leg spasticity False 3 0;0;0 30.556 False ENSG00000115866 ENSG00000115866 HGNC:2678 DARS gene DARS Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal HYPOMYELINATION WITH BRAIN STEM AND SPINAL CORD INVOLVEMENT AND LEG SPASTICITY. 23643384;23643384 False 3 33;67;0 30.556 False ENSG00000115866 ENSG00000115866 HGNC:2678 DARS2 gene DARS2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, OMIM:611105 25655951 False 3 0;0;0 30.556 False ENSG00000117593 ENSG00000117593 HGNC:25538 DARS2 gene DARS2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, 611105;Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) 27604308 False 3 100;0;0 30.556 False ENSG00000117593 ENSG00000117593 HGNC:25538 DARS2 gene DARS2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, OMIM:611105 False 3 100;0;0 30.556 False ENSG00000117593 ENSG00000117593 HGNC:25538 DARS2 gene DARS2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, 611105 False 3 100;0;0 30.556 True ENSG00000117593 ENSG00000117593 HGNC:25538 DBH gene DBH London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dopamine beta-hydroxylase deficiency False 3 100;0;0 30.556 False ENSG00000123454 ENSG00000123454 HGNC:2689 DBT gene DBT Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Maple syrup urine disease, type II, 248600;MAPLE SYRUP URINE DISEASEQ 25529582;24896178;31112740 False 3 100;0;0 30.556 False ENSG00000137992 ENSG00000137992 HGNC:2698 DBT gene DBT London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dihydrolipoamide branched chain transacylase deficiency (Maple syrup urine disease, disorder of branched-chain amino acid metabolism not classified as organic aciduria);Maple syrup urine disease, type II 27604308 False 3 0;0;0 30.556 False ENSG00000137992 ENSG00000137992 HGNC:2698 DCAF17 gene DCAF17 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Woodhouse-Sakati syndrome, OMIM:241080 19026396;20507343;30409855;31726291 False 3 100;0;0 30.556 False ENSG00000115827 ENSG00000115827 HGNC:25784 DCAF17 gene DCAF17 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Woodhouse-Sakati syndrome, 241080;WOODHOUSE-SAKATI SYNDROME (WOSAS) False 3 0;100;0 30.556 False ENSG00000115827 ENSG00000115827 HGNC:25784 DCHS1 gene DCHS1 Other;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Van Maldergem syndrome 1, OMIM:601390 24056717 False 3 33;67;0 30.556 False ENSG00000166341 ENSG00000166341 HGNC:13681 DCPS gene DCPS Expert Review Green;Expert Review;Literature;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Al-Raqad syndrome, 616459;Al-Raqad syndrome (OMIM 616459) 25701870;30289615;25712129 False 3 100;0;0 30.556 False ENSG00000110063 ENSG00000110063 HGNC:29812 DCX gene DCX Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Lissencephaly, X-linked, OMIM:300067;Subcortical laminal heterotopia, X-linked, OMIM:300067 False 3 100;0;0 30.556 False ENSG00000077279 ENSG00000077279 HGNC:2714 DCXR gene DCXR Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal [Pentosuria] 260800 27604308;22042873;23988570 False 3 0;0;0 30.556 False ENSG00000169738 ENSG00000169738 HGNC:18985 DDB1 gene DDB1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual disability 33743206 False 3 100;0;0 30.556 False ENSG00000167986 ENSG00000167986 HGNC:2717 DDB2 gene DDB2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Xeroderma pigmentosum, group E, DDB-negative subtype, 278740 False 3 0;0;0 30.556 False ENSG00000134574 ENSG00000134574 HGNC:2718 DDC gene DDC Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Aromatic L-amino acid decarboxylase deficiency, OMIM:608643;Aromatic L-amino acid decarboxylase deficiency, MONDO:0012084 28100251;30952622;30689738;25597765;24788355 False 3 50;50;0 30.556 False ENSG00000132437 ENSG00000132437 HGNC:2719 DDC gene DDC London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Aromatic L-amino acid decarboxylase deficiency, OMIM:608643;Aromatic L-amino acid decarboxylase deficiency, MONDO:0012084 27604308;24816252;28100251;30952622 False 3 100;0;0 30.556 False ENSG00000132437 ENSG00000132437 HGNC:2719 DDHD2 gene DDHD2 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 54, autosomal recessive, 615033;COMPLEX HEREDITARY SPASTIC PARAPLEGIA False 3 100;0;0 30.556 False ENSG00000085788 ENSG00000085788 HGNC:29106 DDOST gene DDOST Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Ir, OMIM:614507 22305527;34462534 False 3 100;0;0 30.556 False ENSG00000244038 ENSG00000244038 HGNC:2728 DDX11 gene DDX11 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal WARSAW BREAKAGE SYNDROME (WBRS) 20137776;23033317 False 3 33;67;0 30.556 False ENSG00000013573 ENSG00000013573 HGNC:2736 DDX17 gene DDX17 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 39405200 False 3 100;0;0 30.556 False ENSG00000100201 ENSG00000100201 HGNC:2740 DDX23 gene DDX23 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Global developmental delay with speech and behavioral abnormalities, MONDO:0030995 33057194;34050707 False 3 100;0;0 30.556 False ENSG00000174243 ENSG00000174243 HGNC:17347 DDX39B gene DDX39B Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 39918047 False 3 100;0;0 30.556 False ENSG00000198563 ENSG00000198563 HGNC:13917 DDX3X gene DDX3X Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, OMIM:300958 26235985 False 3 100;0;0 30.556 False loss-of-function (truncating variants and curated list of variants) ENSG00000215301 ENSG00000215301 HGNC:2745 DDX59 gene DDX59 Expert Review Green;Literature;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Orofaciodigital syndrome V, 174300 28711741;29127725;23972372;30914295 False 3 100;0;0 30.556 False ENSG00000118197 ENSG00000118197 HGNC:25360 DDX6 gene DDX6 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Generalized hypotonia;Global developmental delay;Intellectual disability;Unsteady gait;Abnormality of the cardiovascular system;Abnormality of the genitourinary system;Abnormality of limbs 31422817 False 3 100;0;0 30.556 False ENSG00000110367 ENSG00000110367 HGNC:2747 DEAF1 gene DEAF1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal ?Dyskinesia, seizures, and intellectual developmental disorder, 617171;Mental retardation, autosomal dominant 24, 615828 21076407;35981081 False 3 100;0;0 30.556 False ENSG00000177030 ENSG00000177030 HGNC:14677 DEGS1 gene DEGS1 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 18, OMIM:618404 30620338;30620337;31186544 False 3 100;0;0 30.556 False ENSG00000143753 ENSG00000143753 HGNC:13709 DEGS1 gene DEGS1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy hypomyelinating 18, MIM 618404);developmental delay 30620337;30620338;31186544 False 3 100;0;0 30.556 False ENSG00000143753 ENSG00000143753 HGNC:13709 DENND5B gene DENND5B Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown DENND5B associated neurodevelopmental disorder 38387458 False 3 100;0;0 30.556 False ENSG00000170456 ENSG00000170456 HGNC:28338 DEPDC5 gene DEPDC5 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Epilepsy, familial focal, with variable foci 1, OMIM:604364 14510823;15329069;10825362;10577924;9851433;23542701 False 3 33;67;0 30.556 False ENSG00000100150 ENSG00000100150 HGNC:18423 DGUOK gene DGUOK London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Deoxyguanosine kinase deficiency (Disorders of purine metabolism);Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), 251880;Mitochondrial DNA Depletion Syndrome;Disorders of mitochondrial DNA maintenance and integrity;Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) 27604308 False 3 100;0;0 30.556 False ENSG00000114956 ENSG00000114956 HGNC:2858 DGUOK gene DGUOK Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal General Leukodystrophy & Mitochondrial Leukoencephalopathy;Mitochondrial Leukoencephalopathy;Mitochondrial DNA depletion syndrome 3 25655951 False 3 0;0;0 30.556 False ENSG00000114956 ENSG00000114956 HGNC:2858 DGUOK gene DGUOK Victorian Clinical Genetics Services;UKGTN;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of mitochondrial DNA maintenance and integrity;Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), 251880;Mitochondrial DNA Depletion Syndrome False 3 100;0;0 30.556 False ENSG00000114956 ENSG00000114956 HGNC:2858 DHCR24 gene DHCR24 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Desmosterolosis, 602398;DESMOSTEROLOSIS False 3 100;0;0 30.556 False ENSG00000116133 ENSG00000116133 HGNC:2859 DHCR24 gene DHCR24 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Desmosterolosis 602398 27604308;11519011;21559050;21671375 False 3 0;0;0 30.556 False ENSG00000116133 ENSG00000116133 HGNC:2859 DHCR7 gene DHCR7 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;IUGR and IGF abnormalities;Smith - Lemli - Opitz syndrome (Disorders of sterol biosynthesis);Disorders of sex development;Cataracts 27604308 False 3 100;0;0 30.556 False ENSG00000172893 ENSG00000172893 HGNC:2860 DHCR7 gene DHCR7 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Smith-Lemli-Opitz syndrome, 270400;SMITH-LEMLI-OPITZ SYNDROME (SLOS) False 3 100;0;0 30.556 False ENSG00000172893 ENSG00000172893 HGNC:2860 DHDDS gene DHDDS NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental delay and seizures with or without movement abnormalities, OMIM:617836 29100083;32654954;33798445;34182312;34382076;34504728 False 3 100;0;0 30.556 False ENSG00000117682 ENSG00000117682 HGNC:20603 DHFR gene DHFR London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dihydrofolate reductase deficiency (Disorders of folate metabolism and transport);Megaloblastic anemia due to dihydrofolate reductase deficiency 27604308 False 3 0;0;0 30.556 False ENSG00000228716 ENSG00000228716 HGNC:2861 DHFR gene DHFR Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Megaloblastic anemia due to dihydrofolate reductase deficiency, 613839;MEGALOBLASTIC ANEMIA DUE TO DIHYDROFOLATE REDUCTASE DEFICIENCY False 3 100;0;0 30.556 False ENSG00000228716 ENSG00000228716 HGNC:2861 DHODH gene DHODH Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Miller syndrome 263750 27604308;19915526;27626380 False 3 0;0;0 30.556 False ENSG00000102967 ENSG00000102967 HGNC:2867 DHPS gene DHPS Expert Review;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Abnormality of head or neck;Seizures;Abnormal muscle tone, Global developmental delay, Intellectual disability, Seizures, EEG abnormality, Behavioral abnormality, Abnormality of head or neck;EEG abnormality;Behavioral abnormality;Abnormal muscle tone;Intellectual disability;Global developmental delay 21389784;30661771;21850436 False 3 100;0;0 30.556 False ENSG00000095059 ENSG00000095059 HGNC:2869 DHRSX gene DHRSX Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type 1DD, OMIM:301133 38821050 False 3 50;0;50 30.556 False ENSG00000169084 ENSG00000169084 HGNC:18399 DHRSX gene DHRSX Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type 1DD, OMIM:301133 38821050 False 3 50;0;50 30.556 False ENSG00000169084 ENSG00000169084 HGNC:18399 DHTKD1 gene DHTKD1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 2-Oxoadipic aciduria (Disorders of histidine, tryptophan or lysine metabolism);2-Aminoadipic aciduria (Disorders of histidine, tryptophan or lysine metabolism);2-aminoadipic and 2-oxoadipic aciduria, 204750 27604308 False 3 25;25;50 30.556 False ENSG00000181192 ENSG00000181192 HGNC:23537 DHTKD1 gene DHTKD1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 2-aminoadipic 2-oxoadipic aciduria, 204750;Charcot-Marie-Tooth disease, axonal, type 2Q, 615025;2-AMINOADIPIC AND 2-OXOADIPIC ACIDURIA False 3 100;0;0 30.556 False ENSG00000181192 ENSG00000181192 HGNC:23537 DHX30 gene DHX30 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown microcephaly, developmental delay intellectual disability, mild cerebral volume loss, hypotonia, seizures, short stature, failure to thrive, and generalized hirsutism 28327206 False 3 33;0;67 30.556 False ENSG00000132153 ENSG00000132153 HGNC:16716 DHX37 gene DHX37 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies, MIM#618731 26539891;31256877;35982159 False 3 100;0;0 30.556 False ENSG00000150990 ENSG00000150990 HGNC:17210 DHX9 gene DHX9 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual developmental disorder, autosomal dominant 75, OMIM:620988 37467750 False 3 100;0;0 30.556 False ENSG00000135829 ENSG00000135829 HGNC:2750 DIAPH1 gene DIAPH1 Expert Review Green;Other Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Seizures, cortical blindness, microcephaly syndrome, 616632; developmental delay; intellectual disability 24781755; 26463574 False 3 0;0;0 30.556 False ENSG00000131504 ENSG00000131504 HGNC:2876 DIS3L2 gene DIS3L2 Expert Review Green;Victorian Clinical Genetics Services;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Gene2Phenotype confirmed gene with ID HPO False 3 100;0;0 30.556 False ENSG00000144535 ENSG00000144535 HGNC:28648 DKC1 gene DKC1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Dyskeratosis congenita, X-linked, 305000;DKC1-RELATED DYSKERATOSIS CONGENITA False 3 33;67;0 30.556 False ENSG00000130826 ENSG00000130826 HGNC:2890 DLAT gene DLAT London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dihydrolipoyl transacetylase deficiency (Disorders of pyruvate metabolism);Pyruvate dehydrogenase E2 deficiency, 245348 27604308 False 3 100;0;0 30.556 False ENSG00000150768 ENSG00000150768 HGNC:2896 DLAT gene DLAT Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pyruvate dehydrogenase E2 deficiency, 245348 False 3 100;0;0 30.556 True ENSG00000150768 ENSG00000150768 HGNC:2896 DLD gene DLD Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dihydrolipoamide dehydrogenase deficiency, OMIM:246900;Leigh syndrome False 3 100;0;0 30.556 True ENSG00000091140 ENSG00000091140 HGNC:2898 DLD gene DLD Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dihydrolipoamide dehydrogenase deficiency, OMIM:246900 False 3 100;0;0 30.556 False ENSG00000091140 ENSG00000091140 HGNC:2898 DLD gene DLD London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dihydrolipoamide dehydrogenase deficiency, OMIM:246900;Dihydrolipoyl dehydrogenase deficiency (Disorders of pyruvate metabolism);Leigh syndrome 27604308 False 3 100;0;0 30.556 False ENSG00000091140 ENSG00000091140 HGNC:2898 DLG3 gene DLG3 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked 90, 300850;MENTAL RETARDATION X-LINKED TYPE 90 (MRX90) False 3 100;0;0 30.556 False ENSG00000082458 ENSG00000082458 HGNC:2902 DLG4 gene DLG4 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual disability;Marfanoid habitus;Intellectual developmental disorder 62 #618793 27479843;25123844;19617690;29460436;23020937;28135719 False 3 40;20;40 30.556 False ENSG00000132535 ENSG00000132535 HGNC:2903 DLL1 gene DLL1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures, OMIM:618709 31353024;31602192 False 3 100;0;0 30.556 False ENSG00000198719 ENSG00000198719 HGNC:2908 DMD gene DMD Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Duchenne muscular dystrophy, 310200Becker muscular dystrophy, 300376Cardiomyopathy, dilated, 3B, 302045;BECKER MUSCULAR DYSTROPHY (BMD) False 3 100;0;0 30.556 False ENSG00000198947 ENSG00000198947 HGNC:2928 DMXL2 gene DMXL2 Expert Review Green;Other Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sensorineural Hearing Loss;ORPHA90636;Epileptic encephalopathy, early infantile, 81, 618663;?Polyendocrine-polyneuropathy syndrome, 616113 25248098;30237576;31688942 False 3 50;0;50 30.556 False ENSG00000104093 ENSG00000104093 HGNC:2938 DNA2 gene DNA2 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 6;615156;Disorders of mitochondrial DNA maintenance and integrity False 3 100;0;0 30.556 False ENSG00000138346 ENSG00000138346 HGNC:2939 DNA2 gene DNA2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Disorders of mitochondrial DNA maintenance and integrity;Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 6;615156 False 3 100;0;0 30.556 True ENSG00000138346 ENSG00000138346 HGNC:2939 DNAJC12 gene DNAJC12 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperphenylalaninemia, mild, non-BH4-deficient, 617384 28132689 False 3 0;0;0 30.556 False ENSG00000108176 ENSG00000108176 HGNC:28908 DNAJC12 gene DNAJC12 Victorian Clinical Genetics Services;Expert Review Green;Other Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperphenylalaninemia, mild, non-BH4-deficient, 617384; Hyperphenylalaninemia, Dystonia, and Intellectual Disability 28132689 False 3 100;0;0 30.556 False ENSG00000108176 ENSG00000108176 HGNC:28908 DNAJC19 gene DNAJC19 Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-methylglutaconic aciduria, type V, 610198 27928778;27426421;16055927 False 3 0;33;67 30.556 False ENSG00000205981 ENSG00000205981 HGNC:30528 DNAJC19 gene DNAJC19 London North GLH;NHS GMS;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-methylglutaconic aciduria, type V, 610198;Disorders of the mitochondrial import system;3-methylglutaconic aciduria, type V 27604308;27426421;16055927;27928778 False 3 100;0;0 30.556 False ENSG00000205981 ENSG00000205981 HGNC:30528 DNAJC19 gene DNAJC19 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of the mitochondrial import system;3-methylglutaconic aciduria, type V, 610198 16055927;22797137;27604308;27928778;27426421 False 3 100;0;0 30.556 False ENSG00000205981 ENSG00000205981 HGNC:30528 DNAJC5 gene DNAJC5 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Ceroid lipofuscinosis, neuronal, 4, Parry type, 162350 27604308;21820099 False 3 0;0;0 30.556 False ENSG00000101152 ENSG00000101152 HGNC:16235 DNM1 gene DNM1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental and epileptic encephalopathy 31, OMIM:616346 0 False 3 0;100;0 30.556 False ENSG00000106976 ENSG00000106976 HGNC:2972 DNM1L gene DNM1L London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Encephalopahty, lethal, due to defective mitochondrial peroxisomal fission, 614388;Encephalopahty, lethal, due to defective mitochondrial peroxisomal fission;Disorders of mitochondrial dynamics, fusion and fission (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) 27604308 False 3 100;0;0 30.556 False ENSG00000087470 ENSG00000087470 HGNC:2973 DNM1L gene DNM1L Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Encephalopahty, lethal, due to defective mitochondrial peroxisomal fission, 614388 PMID: 26825290;17460227 False 3 100;0;0 30.556 True ENSG00000087470 ENSG00000087470 HGNC:2973 DNM1L gene DNM1L Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, MIM#614388 False 3 100;0;0 30.556 False Other ENSG00000087470 ENSG00000087470 HGNC:2973 DNM2 gene DNM2 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Centronuclear myopathy 1, 160150;Charcot-Marie-Tooth disease, axonal type 2M, 606482;Charcot-Marie-Tooth disease, dominant intermediate B, 606482 23813975;https://doi.org/10.1016/j.nmd.2012.06.124 False 3 100;0;0 30.556 True ENSG00000079805 ENSG00000079805 HGNC:2974 DNM2 gene DNM2 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal "Centronuclear myopathy 1 160150;Charcot-Marie-Tooth disease, axonal type 2M 606482;Charcot-Marie-Tooth disease, dominant intermediate B 606482" 18560793;17932957;17636067;17008356;16227997;15731758 False 3 100;0;0 30.556 False ENSG00000079805 ENSG00000079805 HGNC:2974 DNMT3A gene DNMT3A Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Tatton-Brown-Rahman syndrome OMIM:615879;Heyn-Sproul-Jackson syndrome OMIM:618724;MONDO:0032882 24614070 False 3 100;0;0 30.556 False Other ENSG00000119772 ENSG00000119772 HGNC:2978 DNMT3B gene DNMT3B Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Immunodeficiency-centromeric instability-facial anomalies syndrome 1, 242860;IMMUNODEFICIENCY-CENTROMERIC INSTABILITY-FACIAL ANOMALIES SYNDROME 1 False 3 100;0;0 30.556 False ENSG00000088305 ENSG00000088305 HGNC:2979 DOCK3 gene DOCK3 Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia OMIM:618292;neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia MONDO:0032661 29130632;28195318;30976111 False 3 0;100;0 30.556 False ENSG00000088538 ENSG00000088538 HGNC:2989 DOCK4 gene DOCK4 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neuronevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 38526744 False 3 100;0;0 30.556 False ENSG00000128512 ENSG00000128512 HGNC:19192 DOCK6 gene DOCK6 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Adams-Oliver syndrome 2, 614219;intellectual disability, developmental delay 21820096;28884918;27077170;26457590;25824905;25091416;23522784 False 3 67;33;0 30.556 False ENSG00000130158 ENSG00000130158 HGNC:19189 DOCK7 gene DOCK7 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 23; EIEE23 24814191 False 3 0;100;0 30.556 False ENSG00000116641 ENSG00000116641 HGNC:19190 DOHH gene DOHH Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, OMIM:620066 35858628 False 3 100;0;0 30.556 False ENSG00000129932 ENSG00000129932 HGNC:28662 DOLK gene DOLK London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Im 610768;Dolichol kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways) 24144945;22242004 False 3 0;0;0 30.556 False ENSG00000175283 ENSG00000175283 HGNC:23406 DOLK gene DOLK Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal CONGENITAL DISORDERS OF GLYCOSYLATION 17273964;22242004 False 3 33;67;0 30.556 False ENSG00000175283 ENSG00000175283 HGNC:23406 DPAGT1 gene DPAGT1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Ij, 608093Myasthenic syndrome, congenital, with tubular aggregates 2, 614750;MYASTHENIC SYNDROME, CONGENITAL, WITH TUBULAR AGGREGATES 2 False 3 100;0;0 30.556 False ENSG00000172269 ENSG00000172269 HGNC:2995 DPAGT1 gene DPAGT1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Myasthenic syndrome, congenital, 13, with tubular aggregates 614750;UDP-GlcNAc:Dol-P-GlcNac-P transferase deficiency (Disorders of protein N-glycosylation);Congenital disorder of glycosylation, type Ij 608093 27604308 False 3 0;0;0 30.556 False ENSG00000172269 ENSG00000172269 HGNC:2995 DPF2 gene DPF2 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Coffin-Siris syndrome 7, 618027;intellectual disability 26350204;29429572 False 3 40;0;60 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000133884 ENSG00000133884 HGNC:9964 DPH1 gene DPH1 Expert Review Green;Expert Review;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental delay with short stature, dysmorphic facial features, and sparse hair, OMIM:616901 25558065;26220823;27457812;29362492;29410513;30877278 False 3 100;0;0 30.556 False ENSG00000108963 ENSG00000108963 HGNC:3003 DPH5 gene DPH5 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties, OMIM:620070 35482014 False 3 67;33;0 30.556 False ENSG00000117543 ENSG00000117543 HGNC:24270 DPM1 gene DPM1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Ie, OMIM:608799;GDP-Man:Dol-P mannosyltransferase deficiency (Disorders of multiple glycosylation and other glycosylation pathways) 27604308 False 3 0;0;0 30.556 False ENSG00000000419 ENSG00000000419 HGNC:3005 DPM1 gene DPM1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Ie, OMIM:608799 False 3 100;0;0 30.556 False ENSG00000000419 ENSG00000000419 HGNC:3005 DPM2 gene DPM2 Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Iu, OMIM:615042 23109149;26453362;33129689 False 3 100;0;0 30.556 False ENSG00000136908 ENSG00000136908 HGNC:3006 DPM2 gene DPM2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Iu, OMIM:615042 23109149;33129689 False 3 0;0;0 30.556 True ENSG00000136908 ENSG00000136908 HGNC:3006 DPM3 gene DPM3 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15 612937 19576565;28803818 False 3 0;0;0 30.556 False ENSG00000179085 ENSG00000179085 HGNC:3007 DPYD gene DPYD London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dihydropyrimidine dehydrogenase deficiency 274270;Dihydropyrimidine dehydrogenase deficiency (Disorders of pyrimidine metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000188641 ENSG00000188641 HGNC:3012 DPYD gene DPYD Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dihydropyrimidine dehydrogenase deficiency;5-fluorouracil toxicity 274270 False 3 0;0;0 30.556 False ENSG00000188641 ENSG00000188641 HGNC:3012 DPYD gene DPYD Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dihydropyrimidine dehydrogenase deficiency, 2742705-fluorouracil toxicity, 274270 False 3 0;0;100 30.556 False ENSG00000188641 ENSG00000188641 HGNC:3012 DPYS gene DPYS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dihydropyrimidinuria, OMIM:222748;Dihydropyrimidinase deficiency (Disorders of pyrimidine metabolism) 27604308;32600357 False 3 0;0;0 30.556 False ENSG00000147647 ENSG00000147647 HGNC:3013 DPYS gene DPYS Expert Review Green;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dihydropyrimidinuria, OMIM:222748 9266350;17383919;20362666;27604308;26771602;29054612 False 3 100;0;0 30.556 False ENSG00000147647 ENSG00000147647 HGNC:3013 DPYSL5 gene DPYSL5 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities 33894126 False 3 100;0;0 30.556 False ENSG00000157851 ENSG00000157851 HGNC:20637 DTYMK gene DTYMK Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Global developmental delay;Intellectual disability;Microcephaly;Seizures;Global brain atrophy;Cardiorespiratory arrest 31271740;34918187;35346037 False 3 100;0;0 30.556 False ENSG00000168393 ENSG00000168393 HGNC:3061 DYM gene DYM Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dyggve-Melchior-Clausen disease, 223800Smith-McCort dysplasia, 607326;SMITH-MCCORT DYSPLASIA (SMC) False 3 100;0;0 30.556 False ENSG00000141627 ENSG00000141627 HGNC:21317 DYM gene DYM Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Encephalopahty, lethal, due to defective mitochondrial peroxisomal fission, 614388;Dyggve-Melchior-Clausen disease, 223800;Smith-McCort dysplasia, 607326 False 3 0;100;0 30.556 False ENSG00000141627 ENSG00000141627 HGNC:21317 DYNC1H1 gene DYNC1H1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Mental Retardation, Dominant;Charcot-Marie-Tooth disease, axonal, type 20, 614228;Mental retardation, autosomal dominant 13, 614563;Spinal muscular atrophy, lower extremity-predominant, AD, 158600;SPINAL MUSCULAR ATROPHY, LOWER EXTREMITY-PREDOMINANT, AD 25529582;24896178;22459677 False 3 100;0;0 30.556 False ENSG00000197102 ENSG00000197102 HGNC:2961 DYRK1A gene DYRK1A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Mental retardation, autosomal dominant 7, 614104;MENTAL RETARDATION AUTOSOMAL DOMINANT TYPE 7 False 3 100;0;0 30.556 False ENSG00000157540 ENSG00000157540 HGNC:3091 EARS2 gene EARS2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 12, 614924;Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Multiple respiratory chain complex deficiencies (disorders of protein synthesis) 27604308 False 3 100;0;0 30.556 False ENSG00000103356 ENSG00000103356 HGNC:29419 EARS2 gene EARS2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal General Leukodystrophy & Mitochondrial Leukoencephalopathy;Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL);Combined oxidative phosphorylation deficiency 12 25655951 False 3 0;0;0 30.556 False ENSG00000103356 ENSG00000103356 HGNC:29419 EARS2 gene EARS2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 12, 614924 False 3 100;0;0 30.556 True ENSG00000103356 ENSG00000103356 HGNC:29419 EARS2 gene EARS2 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 12, MIM#614924 22492562;23008233 False 3 100;0;0 30.556 False ENSG00000103356 ENSG00000103356 HGNC:29419 EBF3 gene EBF3 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Hypotonia, ataxia, and delayed development syndrome OMIM:617330;hypotonia, ataxia, and delayed development syndrome MONDO:0015021 False 3 100;0;0 30.556 False ENSG00000108001 ENSG00000108001 HGNC:19087 EBP gene EBP London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) MEND syndrome 300960 XLR;Chondrodysplasia punctata, X-linked dominant 302960 XLD;X-linked dominant chondrodysplasia punctata 2 (Disorders of sterol biosynthesis) 27604308 False 3 0;0;0 30.556 False ENSG00000147155 ENSG00000147155 HGNC:3133 EBP gene EBP Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) CHONDRODYSPLASIA PUNCTATA 2, X-LINKED 10391219;10942423;12503101;11038443;10391218 False 3 50;50;0 30.556 False ENSG00000147155 ENSG00000147155 HGNC:3133 ECHS1 gene ECHS1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, OMIM:616277 False 3 100;0;0 30.556 False ENSG00000127884 ENSG00000127884 HGNC:3151 ECHS1 gene ECHS1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, OMIM:616277 False 3 100;0;0 30.556 True ENSG00000127884 ENSG00000127884 HGNC:3151 EDEM3 gene EDEM3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type 2V, OMIM:619493 34143952 False 3 100;0;0 30.556 False ENSG00000116406 ENSG00000116406 HGNC:16787 EDEM3 gene EDEM3 NHS GMS;Expert Review Green;Other Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type 2V, OMIM:619493 34143952 False 3 100;0;0 30.556 False ENSG00000116406 ENSG00000116406 HGNC:16787 EED gene EED Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Cohen-Gibson syndrome, 617561;Human overgrowth syndrome type;Overgrowth with Intellectual disability 25787343;27193220;27868325;28229514;28475857 False 3 100;0;0 30.556 False ENSG00000074266 ENSG00000074266 HGNC:3188 EEF1A2 gene EEF1A2 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted INFANTILE EPILEPTIC ENCEPHALOPATHY 23647072 False 3 100;0;0 30.556 False ENSG00000101210 ENSG00000101210 HGNC:3192 EEF1D gene EEF1D Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with thin corpus callosum, hypotonia, and absent language, OMIM:621150 36576126;30787422;38083972;28097321 False 3 100;0;0 30.556 False ENSG00000104529 ENSG00000104529 HGNC:3211 EEFSEC gene EEFSEC Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with progressive spasticity and brain abnormalities, OMIM:621102 39753114 False 3 100;0;0 30.556 False ENSG00000132394 ENSG00000132394 HGNC:24614 EFTUD2 gene EFTUD2 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Mandibulofacial dysostosis, Guion-Almeida type, 610536;MANDIBULOFACIAL DYSOSTOSIS WITH MICROCEPHALY; MFDM False 3 100;0;0 30.556 False ENSG00000108883 ENSG00000108883 HGNC:30858 EHBP1L1 gene EHBP1L1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal non-immune hydrops fetalis MONDO:0009369 34645488;26833786;https://dmdd.org.uk/mutants/Ehbp1l1 False 3 100;0;0 30.556 False ENSG00000173442 ENSG00000173442 HGNC:30682 EHMT1 gene EHMT1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Kleefstra syndrome, 610253;9Q SUBTELOMERIC DELETION SYNDROME (9Q- SYNDROME) False 3 100;0;0 30.556 False ENSG00000181090 ENSG00000181090 HGNC:24650 EIF2AK2 gene EIF2AK2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, OMIM:618877 32197074;33236446 False 3 100;0;0 30.556 False ENSG00000055332 ENSG00000055332 HGNC:9437 EIF2AK3 gene EIF2AK3 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Wolcott-Rallison syndrome, 226980;WOLCOTT-RALLISON SYNDROME (WRS) False 3 100;0;0 30.556 False ENSG00000172071 ENSG00000172071 HGNC:3255 EIF2B1 gene EIF2B1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukoencephalopathy with vanishing white matter, 603896;Childhood Ataxia with Central Nervous System Hypomyelination;General Leukodystrophy & Mitochondrial Leukoencephalopathy;eIF2B related disorder (Vanishing WM Disease or CACH) 16807905;25655951;15776425 False 3 0;0;0 30.556 False ENSG00000111361 ENSG00000111361 HGNC:3257 EIF2B2 gene EIF2B2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukoencephalopathy with vanishing white matter, 603896;Childhood Ataxia with Central Nervous System Hypomyelination;General Leukodystrophy & Mitochondrial Leukoencephalopathy;eIF2B related disorder (Vanishing WM Disease or CACH);Ovarioleukodystrophy, 603896 25655951 False 3 0;0;0 30.556 False ENSG00000119718 ENSG00000119718 HGNC:3258 EIF2B3 gene EIF2B3 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal General Leukodystrophy & Mitochondrial Leukoencephalopathy;Leukoencephalopathy with vanishing white matter 603896;eIF2B related disorder (Vanishing WM Disease or CACH) 11835386;25655951;19158808 False 3 0;0;0 30.556 False ENSG00000070785 ENSG00000070785 HGNC:3259 EIF2B4 gene EIF2B4 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ovarioleukodystrophy, 603896;Leukoencephaly with vanishing white matter, 603896 11835386;25089094;25655951;12707859;26043506 False 3 0;0;0 30.556 False ENSG00000115211 ENSG00000115211 HGNC:3260 EIF2B5 gene EIF2B5 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukoencephalopathy with vanishing white matter, 603896;Ovarioleukodystrophy, 603896;General Leukodystrophy & Mitochondrial Leukoencephalopathy;eIF2B related disorder (Vanishing WM Disease or CACH) 12325082;25655951;11704758 False 3 0;0;0 30.556 False ENSG00000145191 ENSG00000145191 HGNC:3261 EIF2S3 gene EIF2S3 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Mental retardation, X-linked, syndromic, Borck type, 300987 False 3 33;0;67 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000130741 ENSG00000130741 HGNC:3267 EIF3F gene EIF3F Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mental retardation, autosomal recessive 67, OMIM:618295 30409806 False 3 100;0;0 30.556 False ENSG00000175390 ENSG00000175390 HGNC:3275 EIF4A2 gene EIF4A2 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Neurodevelopmental disorder 36528028 False 3 100;0;0 30.556 False ENSG00000156976 ENSG00000156976 HGNC:3284 EIF4A3 gene EIF4A3 Victorian Clinical Genetics Services;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Robin sequence with cleft mandible and limb anomalies, 268305;Richieri-Costa-Pereira syndrome;intellectual disability 25529582;24360810;29112243;21271648;23376982 False 3 100;0;0 30.556 False ENSG00000141543 ENSG00000141543 HGNC:18683 EIF5A gene EIF5A Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Faundes-Banka syndrome, OMIM:619376 33547280 False 3 100;0;0 30.556 False ENSG00000132507 ENSG00000132507 HGNC:3300 ELAC2 gene ELAC2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 17, 615440;infantile hypertrophic cardiomyopathy, lactic acidosis, and isolated complex I deficiency False 3 100;0;0 30.556 True ENSG00000006744 ENSG00000006744 HGNC:14198 ELAC2 gene ELAC2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal INFANTILE HYPERTROPHIC CARDIOMYOPATHY, LACTIC ACIDOSIS, AND ISOLATED COMPLEX I DEFICIENCY 0 False 3 33;67;0 30.556 False ENSG00000006744 ENSG00000006744 HGNC:14198 ELAC2 gene ELAC2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal infantile hypertrophic cardiomyopathy, lactic acidosis, and isolated complex I deficiency;Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 17, 615440 False 3 100;0;0 30.556 False ENSG00000006744 ENSG00000006744 HGNC:14198 ELFN1 gene ELFN1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder, MONDO:0700092 40576023;34509675;34452636 False 3 100;0;0 30.556 False ENSG00000225968 ENSG00000225968 HGNC:33154 ELOVL1 gene ELOVL1 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, OMIM:618527 23689133;29496980;30487246;32123819 False 3 100;0;0 30.556 False ENSG00000066322 ENSG00000066322 HGNC:14418 ELOVL4 gene ELOVL4 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Stargardt disease 3, 600110Macular dystrophy, autosomal dominant, chromosome 6-linked, 600110Ichthyosis, spastic quadriplegia, and mental retardation, 614457;ICHTHYOSIS, SPASTIC QUADRIPLEGIA, AND MENTAL RETARDATION False 3 100;0;0 30.556 False ENSG00000118402 ENSG00000118402 HGNC:14415 ELP2 gene ELP2 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mental retardation, autosomal recessive 58 617270 21937992;25847581 False 3 33;0;67 30.556 False ENSG00000134759 ENSG00000134759 HGNC:18248 EMC1 gene EMC1 NHS GMS;Expert Review Green;Literature;Literature;Expert Review Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875 29271071;26942288;30914295 False 3 100;0;0 30.556 False ENSG00000127463 ENSG00000127463 HGNC:28957 EMC10 gene EMC10 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with dysmorphic facies and variable seizures, OMIM:619264 32869858;33531666 False 3 100;0;0 30.556 False ENSG00000161671 ENSG00000161671 HGNC:27609 EML1 gene EML1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Band heterotopia, OMIM:600348 28556411; 24859200 False 3 0;100;0 30.556 False ENSG00000066629 ENSG00000066629 HGNC:3330 ENO3 gene ENO3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Glycogen storage disease XIII 27604308;25267339;11506403;25929793 False 3 100;0;0 30.556 False ENSG00000108515 ENSG00000108515 HGNC:3354 ENTPD1 gene ENTPD1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 64, autosomal recessive, OMIM:615683 21937992;24482476;29691679;30652007;35471564;35758610 False 3 50;0;50 30.556 False ENSG00000138185 ENSG00000138185 HGNC:3363 ENTPD1 gene ENTPD1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 64, autosomal recessive, OMIM:615683 35471564 False 3 100;0;0 30.556 False ENSG00000138185 ENSG00000138185 HGNC:3363 EOGT gene EOGT Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Adams-Oliver syndrome 4 OMIM:615297;Adams-Oliver syndrome 4 MONDO:0014124 23522784;31368252;29924900 False 3 100;0;0 30.556 False ENSG00000163378 ENSG00000163378 HGNC:28526 EP300 gene EP300 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted RUBINSTEIN-TAYBI SYNDROME TYPE 2 (RSTS2) 17299436;15706485;20014264;19353645 False 3 100;0;0 30.556 False ENSG00000100393 ENSG00000100393 HGNC:3373 EPB41L3 gene EPB41L3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental disorder with seizures and myelination defects 39292993 False 3 100;0;0 30.556 False ENSG00000082397 ENSG00000082397 HGNC:3380 EPB41L3 gene EPB41L3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental disorder with seizures and myelination defects 39292993 False 3 100;0;0 30.556 False ENSG00000082397 ENSG00000082397 HGNC:3380 EPG5 gene EPG5 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Vici syndrome, 242840;IMMUNODEFICIENCY WITH CLEFT LIP/PALATE, CATARACT, HYPOPIGMENTATION, AND ABSENT CORPUS CALLOSUM 28624465;23222957;26917586;23674064;25331754;23838600;26395118 False 3 0;0;0 30.556 False ENSG00000152223 ENSG00000152223 HGNC:29331 EPG5 gene EPG5 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal IMMUNODEFICIENCY WITH CLEFT LIP/PALATE, CATARACT, HYPOPIGMENTATION, AND ABSENT CORPUS CALLOSUM 3344762;23222957 False 3 33;67;0 30.556 False ENSG00000152223 ENSG00000152223 HGNC:29331 EPM2A gene EPM2A London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Myoclonic epilepsy of Lafora 1, OMIM:254780 27604308 False 3 0;0;0 30.556 False ENSG00000112425 ENSG00000112425 HGNC:3413 EPRS gene EPRS Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal "Leukodystrophy, hypomyelinating, 15, MIM# 617951" 29576217;33805425 False 3 100;0;0 30.556 False ENSG00000136628 ENSG00000136628 HGNC:3418 ERBB4 gene ERBB4 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted intellectual disability MONDO:0001071 33603162;23633123;15219717;30498032 False 3 100;0;0 30.556 False ENSG00000178568 ENSG00000178568 HGNC:3432 ERCC1 gene ERCC1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cerebrooculofacioskeletal syndrome 4, OMIM:610758 17273966 False 3 33;67;0 30.556 False ENSG00000012061 ENSG00000012061 HGNC:3433 ERCC2 gene ERCC2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Xeroderma pigmentosum, group D, 278730Trichothiodystrophy, 601675Cerebrooculofacioskeletal syndrome 2, 610756;CEREBRO-OCULO-FACIO-SKELETAL SYNDROME TYPE 2 (COFS2) False 3 100;0;0 30.556 False ENSG00000104884 ENSG00000104884 HGNC:3434 ERCC3 gene ERCC3 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Xeroderma pigmentosum, group B, 610651Trichothiodystrophy, 601675;XERODERMA PIGMENTOSUM COMPLEMENTATION GROUP B (XP-B) False 3 100;0;0 30.556 False ENSG00000163161 ENSG00000163161 HGNC:3435 ERCC5 gene ERCC5 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Xeroderma pigmentosum, group G, 278780Xeroderma pigmentosum, group G/Cockayne syndrome, 278780;XERODERMA PIGMENTOSUM COMPLEMENTATION GROUP G (XP-G) False 3 100;0;0 30.556 False ENSG00000134899 ENSG00000134899 HGNC:3437 ERCC6 gene ERCC6 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal De Sanctis-Cacchione syndrome;PMID: 26204423;Cockayne syndrome;UV-sensitive syndrome;Cockayne syndrome phenotype and UV-sensitive syndrome;Cockayne syndrome B;UV-sensitive syndrome 1;Intercranial Calcifications;Cockayne syndrome, type B;General Leukodystrophy & Mitochondrial Leukoencephalopathy PMID: 7063265 False 3 0;0;0 30.556 False Other - please provide details in the comments ENSG00000225830 ENSG00000225830 HGNC:3438 ERCC6 gene ERCC6 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal De Sanctis-Cacchione syndrome, OMIM:278800 False 3 100;0;0 30.556 False ENSG00000225830 ENSG00000225830 HGNC:3438 ERCC6L2 gene ERCC6L2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Bone marrow failure syndrome 2, 615715 24507776 False 3 33;67;0 30.556 False ENSG00000182150 ENSG00000182150 HGNC:26922 ERCC8 gene ERCC8 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cockayne syndrome, type A, 216400UV-sensitive syndrome 2, 614621;COCKAYNE SYNDROME TYPE A (CSA) False 3 100;0;0 30.556 False ENSG00000049167 ENSG00000049167 HGNC:3439 ERCC8 gene ERCC8 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal PMID: 26204423;UV-sensitive syndrome;Cockayne syndrome phenotype and UV-sensitive syndrome;Cockayne syndrome, type A;General Leukodystrophy & Mitochondrial Leukoencephalopathy;Cockayne Syndrome 25655951 False 3 0;0;0 30.556 False Other - please provide details in the comments ENSG00000049167 ENSG00000049167 HGNC:3439 ERI1 gene ERI1 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal intellectual disability, MONDO:0001071 36208065;37352860 False 3 100;0;0 30.556 False ENSG00000104626 ENSG00000104626 HGNC:23994 ERLIN2 gene ERLIN2 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 18, autosomal recessive, 611225;intellectual disability;AUTOSOMAL RECESSIVE MENTAL RETARDATION 27824013;25977983;23897027;23109145;23109142;23085305;22554690;21796390;21330303 False 3 40;20;40 30.556 False ENSG00000147475 ENSG00000147475 HGNC:1356 ESAM gene ESAM NHS GMS;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity, OMIM:620371 36996813 False 3 100;0;0 30.556 False ENSG00000149564 ENSG00000149564 HGNC:17474 ESAM gene ESAM NHS GMS;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity, OMIM:620371 36996813 False 3 100;0;0 30.556 False ENSG00000149564 ENSG00000149564 HGNC:17474 ESCO2 gene ESCO2 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Roberts syndrome, 268300SC phocomelia syndrome, 269000;SC PHOCOMELIA SYNDROME (SCPS) False 3 100;0;0 30.556 False ENSG00000171320 ENSG00000171320 HGNC:27230 ETFA gene ETFA Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glutaric acidemia IIA, OMIM:231680;multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282 19249206;1430199;1882842;12815589;17412732;7912128 False 3 33;67;0 30.556 False ENSG00000140374 ENSG00000140374 HGNC:3481 ETFA gene ETFA NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glutaric acidemia IIA, OMIM:231680;multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282 25929793;27604308 False 3 100;0;0 30.556 False ENSG00000140374 ENSG00000140374 HGNC:3481 ETFB gene ETFB NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glutaric acidemia IIB, OMIM:231680;multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282 7912128;12815589;25929793;27604308 False 3 50;0;50 30.556 False ENSG00000105379 ENSG00000105379 HGNC:3482 ETFB gene ETFB Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glutaric acidemia IIB, OMIM:231680;multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282 7912128;12815589;25929793;27604308;30847515;32550677 False 3 33;67;0 30.556 False ENSG00000105379 ENSG00000105379 HGNC:3482 ETFDH gene ETFDH London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Secondary CoQ10 deficiency (Mitochondrial respiratory chain disorders (caused by nuclear variants only));GLUTARIC ACIDURIA TYPE 2C;Glutaric acidemia IIC;Disorders of ubiquinone metabolism and biosynthesis;ETF-ubiquinone oxidoreductase deficiency (Disorders of mitochondrial fatty acid oxidation) 27604308;24816252 False 3 100;0;0 30.556 False ENSG00000171503 ENSG00000171503 HGNC:3483 ETFDH gene ETFDH Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal GLUTARIC ACIDURIA TYPE 2C 0 False 3 33;67;0 30.556 False ENSG00000171503 ENSG00000171503 HGNC:3483 ETFDH gene ETFDH Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glutaric Acidemia IIC;Mitochondrial Leukoencephalopathy 25655951 False 3 0;0;0 30.556 False ENSG00000171503 ENSG00000171503 HGNC:3483 ETFDH gene ETFDH Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of ubiquinone metabolism and biosynthesis;GLUTARIC ACIDURIA TYPE 2C;Glutaric acidemia IIC False 3 100;0;0 30.556 True ENSG00000171503 ENSG00000171503 HGNC:3483 ETHE1 gene ETHE1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex IV deficiency;Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Ethylmalonic encephalopathy, 602473;Ethylmalonic encephalopathy False 3 100;0;0 30.556 True ENSG00000105755 ENSG00000105755 HGNC:23287 ETHE1 gene ETHE1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ethylmalonic encephalopathy, 602473;ETHYLMALONIC ENCEPHALOPATHY False 3 100;0;0 30.556 False ENSG00000105755 ENSG00000105755 HGNC:23287 ETHE1 gene ETHE1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ethylmalonic encephalopathy, 602473;Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Isolated complex IV deficiency;Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors);Ethylmalonic encephalopathy 27604308 False 3 100;0;0 30.556 False ENSG00000105755 ENSG00000105755 HGNC:23287 EXOSC3 gene EXOSC3 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pontocerebellar hypoplasia, type 1B, OMIM:614678 0 False 3 100;0;0 30.556 False ENSG00000107371 ENSG00000107371 HGNC:17944 EXOSC8 gene EXOSC8 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pontocerebellar hypoplasia, type 1C, OMIM:616081 24989451;38017281;34210538 False 3 100;0;0 30.556 False ENSG00000120699 ENSG00000120699 HGNC:17035 EXT1 gene EXT1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Multiple exostoses type I (Disorders of protein O-glycosylation, O-xylosylglycan synthesis deficiencies);Exostoses, multiple, type 1 133700 27604308 False 3 0;0;0 30.556 False ENSG00000182197 ENSG00000182197 HGNC:3512 EXT2 gene EXT2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Multiple exostoses type II (Disorders of protein O-glycosylation, O-xylosylglycan synthesis deficiencies);Exostoses, multiple, type 2 133701;?Seizures, scoliosis, and macrocephaly syndrome 616682 12417417 False 3 0;0;0 30.556 False ENSG00000151348 ENSG00000151348 HGNC:3513 EXT2 gene EXT2 NHS GMS;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Seizures, scoliosis, and macrocephaly syndrome, 616682;autosomal recessive EXT2-related syndrome 25529582;26246518;30997052;30288735 False 3 100;0;0 30.556 False ENSG00000151348 ENSG00000151348 HGNC:3513 EXTL3 gene EXTL3 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Immunoskeletal dysplasia with neurodevelopmental abnormalities, OMIM:617425 28148688;28132690 False 3 100;0;0 30.556 False ENSG00000012232 ENSG00000012232 HGNC:3518 EZH1 gene EZH1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 37433783 False 3 100;0;0 30.556 False Other ENSG00000108799 ENSG00000108799 HGNC:3526 EZH2 gene EZH2 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted WEAVER SYNDROME 2 0 False 3 33;67;0 30.556 False ENSG00000106462 ENSG00000106462 HGNC:3527 FA2H gene FA2H Expert list;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 35, autosomal recessive, OMIM:612319;hereditary spastic paraplegia 35, MONDO:0012866 27604308 False 3 0;0;100 30.556 False ENSG00000103089 ENSG00000103089 HGNC:21197 FA2H gene FA2H Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 35, autosomal recessive OMIM:612319;hereditary spastic paraplegia 35 MONDO:0012866 31837835;30446360;22965561;21592092 False 3 100;0;0 30.556 False ENSG00000103089 ENSG00000103089 HGNC:21197 FAH gene FAH London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Tyrosinemia, type I 27604308 False 3 0;0;0 30.556 False ENSG00000103876 ENSG00000103876 HGNC:3579 FAM126A gene FAM126A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 5, 610532;LEUKODYSTROPHY HYPOMYELINATING TYPE 5 (HLD5) False 3 100;0;0 30.556 False ENSG00000122591 ENSG00000122591 HGNC:24587 FAM126A gene FAM126A Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypomyelination and Congenital Cataract;Leukodystrophy, hypomyelinating, 5, 610532 25655951 False 3 0;0;0 30.556 False ENSG00000122591 ENSG00000122591 HGNC:24587 FAM177A1 gene FAM177A1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 25558065;38767059 False 3 100;0;0 30.556 False ENSG00000151327 ENSG00000151327 HGNC:19829 FAM20C gene FAM20C Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal RAINE SYNDROME 20825432;19250384;17924334 False 3 33;67;0 30.556 False ENSG00000177706 ENSG00000177706 HGNC:22140 FAM50A gene FAM50A Expert Review Green;Literature Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Mental retardation syndrome, X-linked, Armfield type, OMIM:300261;Armfield syndrome, MONDO:0010284 32703943 False 3 100;0;0 30.556 False ENSG00000071859 ENSG00000071859 HGNC:18786 FAR1 gene FAR1 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Peroxisomal fatty acyl-CoA reductase 1 disorder, OMIM:616154 25439727;30561787;33239752 False 3 100;0;0 30.556 False ENSG00000197601 ENSG00000197601 HGNC:26222 FARS2 gene FARS2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Combined oxidative phosphorylation deficiency 14, 614946 27604308 False 3 100;0;0 30.556 False ENSG00000145982 ENSG00000145982 HGNC:21062 FARS2 gene FARS2 Expert Review;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 77, autosomal recessive, 617046;Combined oxidative phosphorylation deficiency 14, 614946 30869852 False 3 100;0;0 30.556 False ENSG00000145982 ENSG00000145982 HGNC:21062 FARS2 gene FARS2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 14, 614946 False 3 100;0;0 30.556 True ENSG00000145982 ENSG00000145982 HGNC:21062 FARSA gene FARSA Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Rajab interstitial lung disease with brain calcifications 2, OMIM:619013 31355908;33598926 False 3 100;0;0 30.556 False ENSG00000179115 ENSG00000179115 HGNC:3592 FARSA gene FARSA Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Rajab interstitial lung disease with brain calcifications 2, OMIM:619013 31355908 False 3 0;0;100 30.556 False ENSG00000179115 ENSG00000179115 HGNC:3592 FASTKD2 gene FASTKD2 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 44, OMIM:618855 False 3 100;0;0 30.556 False ENSG00000118246 ENSG00000118246 HGNC:29160 FASTKD2 gene FASTKD2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 44, OMIM:618855 27604308 False 3 100;0;0 30.556 False ENSG00000118246 ENSG00000118246 HGNC:29160 FAT4 gene FAT4 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal PERIVENTRICULAR NEURONAL HETEROTOPIA 24056717 False 3 33;67;0 30.556 False ENSG00000196159 ENSG00000196159 HGNC:23109 FBP1 gene FBP1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycogen Storage Disease;Glycogen Storage Disorders- Liver;Fructose-1,6-bisphosphatase deficiency (Disorders of gluconeogenesis) 27604308 False 3 0;0;0 30.556 False ENSG00000165140 ENSG00000165140 HGNC:3606 FBRSL1 gene FBRSL1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual disability;Microcephaly;Heart defect;Cleft palate;Contractures;Hearing impairment;Skin creases 32424618 False 3 100;0;0 30.556 False ENSG00000112787 ENSG00000112787 HGNC:29308 FBXL3 gene FBXL3 Expert Review Green;Expert Review;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Short stature;Intellectual developmental disorder with short stature, facial anomalies, and speech defects, 606220;Intellectual disability 30481285 False 3 100;0;0 30.556 False ENSG00000005812 ENSG00000005812 HGNC:13599 FBXL4 gene FBXL4 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) OMIM:615471;mitochondrial DNA depletion syndrome 13 MONDO:0014198 23993194 False 3 33;67;0 30.556 False ENSG00000112234 ENSG00000112234 HGNC:13601 FBXL4 gene FBXL4 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) OMIM:615471;mitochondrial DNA depletion syndrome 13 MONDO:0014198 False 3 100;0;0 30.556 False ENSG00000112234 ENSG00000112234 HGNC:13601 FBXL4 gene FBXL4 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) OMIM:615471;mitochondrial DNA depletion syndrome 13 MONDO:0014198 False 3 100;0;0 30.556 True ENSG00000112234 ENSG00000112234 HGNC:13601 FBXO11 gene FBXO11 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities 618089 30057029;29796876;27620904;27479843;28097321 False 3 100;0;0 30.556 True ENSG00000138081 ENSG00000138081 HGNC:13590 FBXO22 gene FBXO22 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Tayoun-Maawali syndrome, OMIM:621184 40215970 False 3 100;0;0 30.556 False ENSG00000167196 ENSG00000167196 HGNC:13593 FBXO28 gene FBXO28 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Developmental and epileptic encephalopathy 100, OMIM:619777;developmental and epileptic encephalopathy 100, MONDO:0030695 30160831;33280099 False 3 100;0;0 30.556 False ENSG00000143756 ENSG00000143756 HGNC:29046 FBXO31 gene FBXO31 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal ?Mental retardation, autosomal recessive 45, OMIM:615979;Intellectual disability, autosomal dominant 24623383;32989326;33675180 False 3 100;0;0 30.556 False ENSG00000103264 ENSG00000103264 HGNC:16510 FBXW11 gene FBXW11 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental, jaw, eye, and digital syndrome, OMIM:618914;neurodevelopmental, jaw, eye, and digital syndrome, MONDO:003005 31402090 False 3 100;0;0 30.556 False ENSG00000072803 ENSG00000072803 HGNC:13607 FBXW7 gene FBXW7 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Developmental delay, hypotonia, and impaired language, OMIM:620012 33057194;35395208;30885698;26482194;19963109;20332316 False 3 75;25;0 30.556 False ENSG00000109670 ENSG00000109670 HGNC:16712 FDX2 gene FDX2 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy OMIM:251900;mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy MONDO:0020714 24281368;28803783;30010796 False 3 50;50;0 30.556 False ENSG00000267673 ENSG00000267673 HGNC:30546 FDX2 gene FDX2 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy OMIM:251900;mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy MONDO:0020714 24281368;28803783;30010796 False 3 50;50;0 30.556 False ENSG00000267673 ENSG00000267673 HGNC:30546 FDXR gene FDXR Expert Review Green;Literature;Expert Review;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Auditory neuropathy and optic atrophy, OMIM:617717;Multiple mitochondrial dysfunctions syndrome 9B, OMIM:620887 28965846 False 3 100;0;0 30.556 False ENSG00000161513 ENSG00000161513 HGNC:3642 FDXR gene FDXR Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Auditory neuropathy and optic atrophy, OMIM:617717;Multiple mitochondrial dysfunctions syndrome 9B, OMIM:620887 28965846 False 3 100;0;0 30.556 True ENSG00000161513 ENSG00000161513 HGNC:3642 FECH gene FECH Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Protoporphyria, erythropoietic, 1, OMIM:177000;protoporphyria, erythropoietic, 1, MONDO:0008319 7857832;11753383;16385445;16911284;27604308;32873934;38940544;39969427 False 3 100;0;0 30.556 False ENSG00000066926 ENSG00000066926 HGNC:3647 FEM1B gene FEM1B Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with behavioral, ear, and skeletal abnormalities, OMIM:621263;neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 31036916;38465576 False 3 67;0;33 30.556 False ENSG00000169018 ENSG00000169018 HGNC:3649 FGD1 gene FGD1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Aarskog-Scott syndrome, 305400Mental retardation, X-linked syndromic 16, 305400;AARSKOG-SCOTT SYNDROME (AAS) False 3 100;0;0 30.556 False ENSG00000102302 ENSG00000102302 HGNC:3663 FGF12 gene FGF12 Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Epileptic encephalopathy, early infantile, 47, 617166 25529582;27164707;27830185;27872899 False 3 100;0;0 30.556 False Other - please provide details in the comments ENSG00000114279 ENSG00000114279 HGNC:3668 FGFR2 gene FGFR2 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown "Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis 207410;Apert syndrome 101200;Beare-Stevenson cutis gyrata syndrome 123790;Bent bone dysplasia syndrome 614592;Craniofacial-skeletal-dermatologic dysplasia 101600;Craniosynostosis, nonspecific;Crouzon syndrome 123500;Gastric cancer, somatic 613659;Jackson-Weiss syndrome 123150;LADD syndrome 149730;Pfeiffer syndrome 101600;Saethre-Chotzen syndrome 101400;Scaphocephaly and Axenfeld-Rieger anomaly;Scaphocephaly, maxillary retrusion, and mental retardation 609579" 27604308 False 3 0;0;0 30.556 False ENSG00000066468 ENSG00000066468 HGNC:3689 FH gene FH London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Fumarase deficiency, OMIM:606812;Disorders of the citric acid cycle 27604308 False 3 100;0;0 30.556 False ENSG00000091483 ENSG00000091483 HGNC:3700 FH gene FH Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Fumarase deficiency, OMIM:606812 False 3 100;0;0 30.556 False ENSG00000091483 ENSG00000091483 HGNC:3700 FH gene FH Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Fumarase deficiency, OMIM:606812 False 3 100;0;0 30.556 True ENSG00000091483 ENSG00000091483 HGNC:3700 FIBP gene FIBP Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Thauvin-Robinet-Faivre syndrome, OMIM:617107;tall stature-intellectual disability-renal anomalies syndrome, MONDO:0014918 26660953;27183861;37876348;37218527 False 3 50;50;0 30.556 False ENSG00000172500 ENSG00000172500 HGNC:3705 FIG4 gene FIG4 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Charcot-Marie-Tooth disease, type 4J, OMIM:611228;Charcot-Marie-Tooth disease type 4J MONDO:0012640;Yunis Varon syndrome OMIM:216340;Yunis-Varon syndrome MONDO:0008995 17572665;25529582 False 3 33;67;0 30.556 False ENSG00000112367 ENSG00000112367 HGNC:16873 FIG4 gene FIG4 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Charcot-Marie-Tooth disease, type 4J, OMIM:611228;Yunis-Varon syndrome, OMIM:216340;leukoencephalopathy, HP:0002352 30740813;29688489 False 3 100;0;0 30.556 False ENSG00000112367 ENSG00000112367 HGNC:16873 FILIP1 gene FILIP1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal intellectual disability, MONDO:0001071 36344539;37163662 False 3 100;0;0 30.556 False ENSG00000118407 ENSG00000118407 HGNC:21015 FKRP gene FKRP Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5, 613153Muscular dystrophy-dystroglycanopathy (congenital with or without mental retardation), type B, 5,606612Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5, 607155;MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY LIMB-GIRDLE TYPE C5 (MDDGC5) False 3 100;0;0 30.556 False ENSG00000181027 ENSG00000181027 HGNC:17997 FKRP gene FKRP London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy-dystroglycanopathy (congenital with or without mental retardation), type B, 5 606612;Fukutin-related protein deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies);Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5 607155;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5 613153 27604308 False 3 0;0;0 30.556 False ENSG00000181027 ENSG00000181027 HGNC:17997 FKTN gene FKTN Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4, 253800Muscular dystrophy-dystroglycanopathy (congenital without mental retardation), type B, 4, 613152Cardiomyopathy, dilated, 1X, 611615Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4, 611588;MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITHOUT MENTAL RETARDATION TYPE B4 (MDDGB4) False 3 100;0;0 30.556 False ENSG00000106692 ENSG00000106692 HGNC:3622 FKTN gene FKTN London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy-dystroglycanopathy (congenital without mental retardation), type B, 4 613152;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 253800;Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4 611588;Fukutin deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) 27604308 False 3 0;0;0 30.556 False ENSG00000106692 ENSG00000106692 HGNC:3622 FLAD1 gene FLAD1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Multiple acyl-CoA dehydrogenase deficiencies (MADDs) PubMed: 27259049 False 3 0;100;0 30.556 False ENSG00000160688 ENSG00000160688 HGNC:24671 FLAD1 gene FLAD1 Victorian Clinical Genetics Services;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Multiple acyl-CoA dehydrogenase deficiencies (MADDs) PubMed: 27259049 False 3 0;100;0 30.556 True ENSG00000160688 ENSG00000160688 HGNC:24671 FLVCR1 gene FLVCR1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with microcephaly, absent speech, and hypotonia, OMIM:621060;neurodevelopmental disorder with microcephaly, absent speech, and hypotonia, MONDO:0976126 30656474;22279524;21267618;21070897;9409377;30444160;39306721 False 3 50;33;17 30.556 False ENSG00000162769 ENSG00000162769 HGNC:24682 FLVCR2 gene FLVCR2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal PROLIFERATIVE VASCULOPATHY AND HYDRAENCEPHALY-HYDROCEPHALY SYNDROME 20206334;19635601;20518025 False 3 33;67;0 30.556 False ENSG00000119686 ENSG00000119686 HGNC:20105 FLVCR2 gene FLVCR2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Proliferative vasculopathy and hydraencephaly-hydrocephaly syndrome, 225790 False 3 0;0;0 30.556 False ENSG00000119686 ENSG00000119686 HGNC:20105 FMN2 gene FMN2 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal NONSYNDROMIC AUTOSOMAL-RECESSIVE INTELLECTUAL DISABILITY 25480035 False 3 100;0;0 30.556 False ENSG00000155816 ENSG00000155816 HGNC:14074 FMO3 gene FMO3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Trimethylaminuria (Disorders and variants of enzymes that oxidise xenobiotics other than cytochrome P450) 27604308 False 3 100;0;0 30.556 False ENSG00000007933 ENSG00000007933 HGNC:3771 FMR1 gene FMR1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory;UKGTN Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Fragile X syndrome, OMIM:300624;Fragile X tremor/ataxia syndrome, OMIM:300623 21267007;25171808;28176767;29178241 False 3 100;0;0 30.556 False Other - please provide details in the comments ENSG00000102081 ENSG00000102081 HGNC:3775 FOLR1 gene FOLR1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal NEURODEGENERATION DUE TO CEREBRAL FOLATE TRANSPORT DEFICIENCY 21937992;19732866 False 3 33;67;0 30.556 False ENSG00000110195 ENSG00000110195 HGNC:3791 FOLR1 gene FOLR1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodegeneration due to cerebral folate transport deficiency, 613068;Cerebral folate deficiency due to FOLR1 deficiency (Disorders of folate metabolism and transport) 27604308 False 3 0;0;0 30.556 False ENSG00000110195 ENSG00000110195 HGNC:3791 FOLR1 gene FOLR1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodegeneration due to cerebral folate transport deficiency, 613068 False 3 0;0;0 30.556 False ENSG00000110195 ENSG00000110195 HGNC:3791 FOSL2 gene FOSL2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Aplasia cutis-enamel dysplasia syndrome, OMIM:620789 36197437 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000075426 ENSG00000075426 HGNC:3798 FOXG1 gene FOXG1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Rett Syndrome, congenital variant OMIM:613454;Rett syndrome, congenital variant MONDO:0013270 21441262;19564653;19578037;27029630;18571142 False 3 100;0;0 30.556 False ENSG00000176165 ENSG00000176165 HGNC:3811 FOXP1 gene FOXP1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Mental retardation with language impairment and autistic features, 613670;Mental Retardation with Language Impairment and Autistic Features;MENTAL RETARDATION WITH LANGUAGE IMPAIRMENT AND AUTISTIC FEATURES (MRLIAF) False 3 100;0;0 30.556 False ENSG00000114861 ENSG00000114861 HGNC:3823 FOXP2 gene FOXP2 Victorian Clinical Genetics Services;Expert Review Green;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Speech-Language Disorder 1;SPEECH-LANGUAGE DISORDER 1 False 3 100;0;0 30.556 False ENSG00000128573 ENSG00000128573 HGNC:13875 FOXRED1 gene FOXRED1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial Diseases;Leigh syndrome due to mitochondrial complex I deficiency, 256000Mitochondrial complex I deficiency, 252010;Isolated complex I deficiency;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors);Mitochondrial Respiratory Chain Complex I Deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000110074 ENSG00000110074 HGNC:26927 FOXRED1 gene FOXRED1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 19, OMIM:618241;mitochondrial complex 1 deficiency, nuclear type 19, MONDO:0032624 20858599;10080174;17262856;23553477;20382551;22499348;12616398;15159508;11349233;11181577;21203893;9837812;10330338;19185523;16200211;15824269;10944442;20818383;9463323 False 3 33;67;0 30.556 False ENSG00000110074 ENSG00000110074 HGNC:26927 FOXRED1 gene FOXRED1 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Leigh syndrome due to mitochondrial complex I deficiency, 256000Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex I Deficiency False 3 100;0;0 30.556 False ENSG00000110074 ENSG00000110074 HGNC:26927 FRA10AC1 gene FRA10AC1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities, OMIM:620113 34694367;35871492;35821753 False 3 100;0;0 30.556 False ENSG00000148690 ENSG00000148690 HGNC:1162 FRMD5 gene FRMD5 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with eye movement abnormalities and ataxia, OMIM:620094 36206744 False 3 100;0;0 30.556 False ENSG00000171877 ENSG00000171877 HGNC:28214 FRMPD4 gene FRMPD4 Expert Review Green;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Mental retardation, X-linked 104, 300983;global developmental delay;intellectual disability 26350204;24896178;25644381;20613765;23871722;29267967 False 3 20;40;40 30.556 False ENSG00000169933 ENSG00000169933 HGNC:29007 FTCD gene FTCD Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glutamate formiminotransferase deficiency 229100 27604308;12815595;29178637 False 3 0;0;0 30.556 False ENSG00000160282 ENSG00000160282 HGNC:3974 FTCD gene FTCD Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal GLUTAMATE FORMIMINOTRANSFERASE DEFICIENCY (FIGLU-URIA) 12815595 False 3 33;67;0 30.556 False ENSG00000160282 ENSG00000160282 HGNC:3974 FTSJ1 gene FTSJ1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked 9, 309549;MENTAL RETARDATION X-LINKED TYPE 44 (MRX44) False 3 100;0;0 30.556 False ENSG00000068438 ENSG00000068438 HGNC:13254 FUCA1 gene FUCA1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Fucosidosis, 230000;FUCOSIDOSIS (FUCA1D);intellectual disability 8401503;9762612;8097260;2012122;2642067;1281988 False 3 100;0;0 30.556 False ENSG00000179163 ENSG00000179163 HGNC:4006 FUCA1 gene FUCA1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Fucosidosis;General Leukodystrophy & Mitochondrial Leukoencephalopathy 25655951 False 3 0;0;0 30.556 False ENSG00000179163 ENSG00000179163 HGNC:4006 FUCA1 gene FUCA1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Fucosidosis, 230000 False 3 0;0;0 30.556 False ENSG00000179163 ENSG00000179163 HGNC:4006 FUK gene FUK Expert Review Green;NHS GMS;Expert Review;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation with defective fucosylation 2, OMIM:618324 30503518;35718084;36426412 False 3 67;33;0 30.556 False ENSG00000157353 ENSG00000157353 HGNC:29500 FUK gene FUK Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation with defective fucosylation 2 OMIM:618324;congenital disorder of glycosylation with defective fucosylation 2 MONDO:0020777 30503518;35718084;36426412 False 3 67;33;0 30.556 False ENSG00000157353 ENSG00000157353 HGNC:29500 FUT8 gene FUT8 Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation with defective fucosylation, 618005;Intellectual disability 29304374;15917429 False 3 100;0;0 30.556 False ENSG00000033170 ENSG00000033170 HGNC:4019 FUT8 gene FUT8 Expert Review Green;Expert Review;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation with defective fucosylation, 618005 29304374 False 3 100;0;0 30.556 False ENSG00000033170 ENSG00000033170 HGNC:4019 FXN gene FXN Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Friedreich ataxia OMIM:229300;Friedreich ataxia with retained reflexes OMIM:229300;Friedreich ataxia 1 MONDO:0100340 27604308 False 3 75;0;25 30.556 False ENSG00000165060 ENSG00000165060 HGNC:3951 FZR1 gene FZR1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental and epileptic encephalopathy 109, OMIM:620145 31318984;34788397 False 3 100;0;0 30.556 False ENSG00000105325 ENSG00000105325 HGNC:24824 G6PC gene G6PC London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycogen storage disease Ia, OMIM:232200 27604308 False 3 0;0;0 30.556 False ENSG00000131482 ENSG00000131482 HGNC:4056 G6PC3 gene G6PC3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dursun syndrome False 3 0;0;0 30.556 False ENSG00000141349 ENSG00000141349 HGNC:24861 GAA gene GAA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycogen storage disease II, 232300 False 3 100;0;0 30.556 False ENSG00000171298 ENSG00000171298 HGNC:4065 GABBR2 gene GABBR2 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Developmental and epileptic encephalopathy 59, OMIM:617904;eurodevelopmental disorder with poor language and loss of hand skills, OMIM:617903 29100083;28061363;28135719;28856709;29369404;29377213;39028675 False 3 0;50;50 30.556 False ENSG00000136928 ENSG00000136928 HGNC:4507 GABRA1 gene GABRA1 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted JUVENILE MYOCLONIC EPILEPSY 23934111 False 3 33;67;0 30.556 False ENSG00000022355 ENSG00000022355 HGNC:4075 GABRA2 gene GABRA2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Epileptic encephalopathy, early infantile, 78, 618557;intellectual disability;developmental delay 29422393;29961870;31032849;31032848;doi.org/10.1101/678219 False 3 100;0;0 30.556 False ENSG00000151834 ENSG00000151834 HGNC:4076 GABRA5 gene GABRA5 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Epileptic encephalopathy, early infantile, 79, 618559;developmental delay 29961870;31056671 False 3 100;0;0 30.556 False ENSG00000186297 ENSG00000186297 HGNC:4079 GABRB2 gene GABRB2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Epileptic encephalopathy, infantile or early childhood, 2, 617829;intellectual disability 25124326;27789573 False 3 0;100;0 30.556 False ENSG00000145864 ENSG00000145864 HGNC:4082 GABRB3 gene GABRB3 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted CHILDHOOD ABSENCE EPILEPSY TYPE 5 18514161 False 3 33;67;0 30.556 False ENSG00000166206 ENSG00000166206 HGNC:4083 GABRD gene GABRD Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted {Epilepsy, idiopathic generalized, 10}, OMIM:613060;{Epilepsy, juvenile myoclonic, susceptibility to}, OMIM:613060 34633442 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000187730 ENSG00000187730 HGNC:4084 GABRG2 gene GABRG2 Expert Review Green;Victorian Clinical Genetics Services;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Epilepsy, generalized, with febrile seizures plus, type 3 611277;Febrile seizures, familial, 8 611277;{Epilepsy, childhood absence, susceptibility to, 2} 607681 25124326;28460589 False 3 100;0;0 30.556 False ENSG00000113327 ENSG00000113327 HGNC:4087 GABRG2 gene GABRG2 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Febrile seizures, familial, 8 611277;Epilepsy, generalized, with febrile seizures plus, type 3 611277;{Epilepsy, childhood absence, susceptibility to, 2} 607681 23708187;16510738;15342642;34957497 False 3 100;0;0 30.556 False ENSG00000113327 ENSG00000113327 HGNC:4087 GAD1 gene GAD1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal "?Cerebral palsy, spastic quadriplegic, 1 603513;Developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele" 15571623;26503795;24896178;26350204;https://doi-org.ezproxy.library.qmul.ac.uk/10.1093/brain/awaa085 False 3 33;0;67 30.556 False ENSG00000128683 ENSG00000128683 HGNC:4092 GALC gene GALC London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Krabbe disease, OMIM:245200 27604308 False 3 0;0;0 30.556 False ENSG00000054983 ENSG00000054983 HGNC:4115 GALC gene GALC Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Krabbe disease, OMIM:245200 8786069;8297359;20886637;21070211 False 3 33;67;0 30.556 False ENSG00000054983 ENSG00000054983 HGNC:4115 GALC gene GALC Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Krabbe disease, OMIM:245200 False 3 0;0;0 30.556 False ENSG00000054983 ENSG00000054983 HGNC:4115 GALE gene GALE London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;Uridine diphosphate galactose-4-epimerase deficiency (Disorders of galactose metabolism);Galactose epimerase deficiency, OMIM:230350;MONDO:0009257 27604308 False 3 0;0;0 30.556 False ENSG00000117308 ENSG00000117308 HGNC:4116 GALE gene GALE Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Galactose epimerase deficiency, 230350;EPIMERASE-DEFICIENCY GALACTOSEMIA (EDG) False 3 100;0;0 30.556 False ENSG00000117308 ENSG00000117308 HGNC:4116 GALK1 gene GALK1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Galactokinase deficiency with cataracts, 230200 False 3 0;0;0 30.556 False ENSG00000108479 ENSG00000108479 HGNC:4118 GALM gene GALM Expert Review Green;Literature;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Galactosemia IV, OMIM:618881;MONDO:0030105 30451973;30910422 False 3 100;0;0 30.556 False ENSG00000143891 ENSG00000143891 HGNC:24063 GALNS gene GALNS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MUCOPOLYSACCHARIDOSIS TYPE 4A;Mucopolysaccharidosis Type IVA;Mucopolysaccharidosis IVA, 253000;Mucopolysaccharidosis, Type IV;MPS IVA, Morquio A disease (MPS IV, Morquio disease) 27604308 False 3 0;0;0 30.556 False ENSG00000141012 ENSG00000141012 HGNC:4122 GALNT2 gene GALNT2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIt 618885 27508872;32293671 False 3 100;0;0 30.556 False ENSG00000143641 ENSG00000143641 HGNC:4124 GALNT2 gene GALNT2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIt 618885 27508872;32293671 False 3 100;0;0 30.556 False ENSG00000143641 ENSG00000143641 HGNC:4124 GALNT3 gene GALNT3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Polypeptide N-acetylgalactosaminyl transferase deficiency (Disorders of protein O-glycosylation, O-N-acetylgalactosaminylglycan synthesis deficiencies);Tumoral calcinosis, hyperphosphatemic, familial 211900 15133511 False 3 0;0;0 30.556 False ENSG00000115339 ENSG00000115339 HGNC:4125 GALT gene GALT London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Galactosemia, OMIM:230400 27604308 False 3 0;0;0 30.556 False ENSG00000213930 ENSG00000213930 HGNC:4135 GALT gene GALT Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Galactosemia, OMIM:230400 False 3 100;0;0 30.556 False ENSG00000213930 ENSG00000213930 HGNC:4135 GAMT gene GAMT Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cerebral creatine deficiency syndrome 2, 612736;GUANIDINOACETATE METHYLTRANSFERASE DEFICIENCY (GAMT DEFICIENCY) False 3 100;0;0 30.556 False ENSG00000130005 ENSG00000130005 HGNC:4136 GAMT gene GAMT Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cerebral creatine deficiency syndrome 2 612736 27604308;17101918;15651030;8651275 False 3 100;0;0 30.556 False ENSG00000130005 ENSG00000130005 HGNC:4136 GAN gene GAN Expert Review Green;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Giant axonal neuropathy-1, OMIM:256850 18595793;19231187;20301315 False 3 100;0;0 30.556 False ENSG00000261609 ENSG00000261609 HGNC:4137 GARS gene GARS Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Charcot-Marie-Tooth disease, type 2D;Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Neuropathy, distal hereditary motor, type VA False 3 100;0;0 30.556 False ENSG00000106105 ENSG00000106105 HGNC:4162 GARS gene GARS Victorian Clinical Genetics Services;Expert Review Green;Expert list;Expert Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Charcot-Marie-Tooth disease, type 2D;Neuropathy, distal hereditary motor, type VA False 3 100;0;0 30.556 True ENSG00000106105 ENSG00000106105 HGNC:4162 GATAD2B gene GATAD2B Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Mental retardation, autosomal dominant 18, 615074;NONSPECIFIC SEVERE ID False 3 100;0;0 30.556 False ENSG00000143614 ENSG00000143614 HGNC:30778 GATM gene GATM London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Arginine:glycine amidinotransferase deficiency (Mitochondrial respiratory chain disorders (caused by nuclear variants only), disorders of creatinine metabolism);arginine:glycine amidinotransferase deficiency;Cerebral creatine deficiency syndrome 3, 612718 27604308 False 3 100;0;0 30.556 False ENSG00000171766 ENSG00000171766 HGNC:4175 GATM gene GATM Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cerebral creatine deficiency syndrome 3, OMIM:612718 False 3 100;0;0 30.556 False ENSG00000171766 ENSG00000171766 HGNC:4175 GBA gene GBA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Gaucher disease, perinatal lethal, 608013;Gaucher disease, type III, 231000;Gaucher disease, type II, 230900;Gaucher disease, type I, 230800;Gaucher disease, type IIIC, 231005;Gaucher disease;Gaucher disease (Sphingolipidoses) 27604308 False 3 0;0;0 30.556 False ENSG00000177628 ENSG00000177628 HGNC:4177 GBE1 gene GBE1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Polyglucosan body disease, adult form, OMIM:263570;General Leukodystrophy & Mitochondrial Leukoencephalopathy 25655951 False 3 0;0;0 30.556 False ENSG00000114480 ENSG00000114480 HGNC:4180 GBE1 gene GBE1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycogen storage disease IV, OMIM:232500;Polyglucosan body disease, adult form, OMIM:263570 27604308 False 3 100;0;0 30.556 False ENSG00000114480 ENSG00000114480 HGNC:4180 GCDH gene GCDH London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glutaricaciduria, type I, 231670 False 3 0;0;0 30.556 False ENSG00000105607 ENSG00000105607 HGNC:4189 GCDH gene GCDH Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal GLUTARICACIDEMIA TYPE 1 8900228;10699052;8900227;11174631;7795610 False 3 100;0;0 30.556 False ENSG00000105607 ENSG00000105607 HGNC:4189 GCH1 gene GCH1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230Hyperphenylalaninemia, BH4-deficient, B, 233910;DYSTONIA TYPE 5 (DYT5) False 3 100;0;0 30.556 False ENSG00000131979 ENSG00000131979 HGNC:4193 GCH1 gene GCH1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Dystonia, DOPA-responsive, with or without hyperphenylalaninemia 27604308 False 3 0;0;0 30.556 False ENSG00000131979 ENSG00000131979 HGNC:4193 GCLC gene GCLC London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Gamma-glutamylcysteine synthetase deficiency (Disorders of the gamma-glutamyl cycle);Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency 230450 27604308 False 3 100;0;0 30.556 False ENSG00000001084 ENSG00000001084 HGNC:4311 GCSH gene GCSH Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 7, OMIM:620423;Glycine encephalopathy;Transient neonatal hyperglycinemia 27604308;16450403;36190515 False 3 67;0;33 30.556 False ENSG00000140905 ENSG00000140905 HGNC:4208 GCSH gene GCSH Expert Review Green;NHS GMS;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 7, OMIM:620423;Glycine encephalopathy;Transient neonatal hyperglycinemia 36190515 False 3 50;0;50 30.556 False ENSG00000140905 ENSG00000140905 HGNC:4208 GDAP1 gene GDAP1 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Charcot-Marie-Tooth disease, axonal, type 2K, OMIM:607831;Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, OMIM:607706;Charcot-Marie-Tooth disease, recessive intermediate, A, OMIM:608340;Charcot-Marie-Tooth disease, type 4A, OMIM:214400 PMID: 11743579 False 3 100;0;0 30.556 True ENSG00000104381 ENSG00000104381 HGNC:15968 GDAP1 gene GDAP1 Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Charcot-Marie-Tooth disease, axonal, type 2K, OMIM:607831;Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, OMIM:607706;Charcot-Marie-Tooth disease, recessive intermediate, A, OMIM:608340;Charcot-Marie-Tooth disease, type 4A, OMIM:214400 PMID: 11743579 False 3 67;0;33 30.556 False ENSG00000104381 ENSG00000104381 HGNC:15968 GDI1 gene GDI1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked 41, 300849;MENTAL RETARDATION X-LINKED TYPE 41 (MRX41) False 3 100;0;0 30.556 False ENSG00000203879 ENSG00000203879 HGNC:4226 GEMIN4 gene GEMIN4 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities, OMIM:617913 25558065;27878435;35052432;35861185 False 3 100;0;0 30.556 False ENSG00000179409 ENSG00000179409 HGNC:15717 GEMIN5 gene GEMIN5 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction, OMIM:619333 33963192 False 3 100;0;0 30.556 False ENSG00000082516 ENSG00000082516 HGNC:20043 GFAP gene GFAP Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown General Leukodystrophy & Mitochondrial Leukoencephalopathy 25655951 False 3 0;0;0 30.556 False Other - please provide details in the comments ENSG00000131095 ENSG00000131095 HGNC:4235 GFAP gene GFAP Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Alexander disease, 203450;ALEXANDER DISEASE 12975300;11567214;12034796;12447932;11138011;14557587;25529582;24896178 False 3 100;0;0 30.556 False ENSG00000131095 ENSG00000131095 HGNC:4235 GFER gene GFER Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay, 613076;Intellectual disability 19409522;26018198;28155230 False 3 33;0;67 30.556 False ENSG00000127554 ENSG00000127554 HGNC:4236 GFER gene GFER London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Disorders of the mitochondrial import system;Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay,613076;Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) 27604308 False 3 100;0;0 30.556 False ENSG00000127554 ENSG00000127554 HGNC:4236 GFER gene GFER Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Disorders of the mitochondrial import system;Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay,613076 PMID: 26018198;19409522 False 3 100;0;0 30.556 False ENSG00000127554 ENSG00000127554 HGNC:4236 GFM1 gene GFM1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 1, 609060 False 3 100;0;0 30.556 True ENSG00000168827 ENSG00000168827 HGNC:13780 GFM1 gene GFM1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 1 17160893 False 3 33;67;0 30.556 False ENSG00000168827 ENSG00000168827 HGNC:13780 GFM1 gene GFM1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal General Leukodystrophy & Mitochondrial Leukoencephalopathy;Combined oxidative phosphorylation deficiency 1;Mitochondrial Leukoencephalopathy 25655951 False 3 0;0;0 30.556 False ENSG00000168827 ENSG00000168827 HGNC:13780 GFM1 gene GFM1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 1, 609060;Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) 27604308 False 3 100;0;0 30.556 False ENSG00000168827 ENSG00000168827 HGNC:13780 GFM2 gene GFM2 Expert Review Green;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 39, OMIM:618397 22700954;26016410;29075935 False 3 100;0;0 30.556 False ENSG00000164347 ENSG00000164347 HGNC:29682 GFM2 gene GFM2 Expert Review Green;Victorian Clinical Genetics Services;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 39, OMIM:618397;Early-onset neurological presentations of mitochondrial disease and impaired expression of OXPHOS subunits 29075935;22700954;26016410 False 3 100;0;0 30.556 False ENSG00000164347 ENSG00000164347 HGNC:29682 GFPT1 gene GFPT1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Myasthenia, congenital, 12, with tubular aggregates(Disorders of protein N-glycosylation) 610542;Congenital myasthenic sydrome (Disorders of protein N-glycosylation) 27604308 False 3 0;0;0 30.556 False ENSG00000198380 ENSG00000198380 HGNC:4241 GIF gene GIF London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intrinsic factor deficiency 27604308 False 3 0;0;0 30.556 False ENSG00000134812 ENSG00000134812 HGNC:4268 GJA1 gene GJA1 Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Oculodentodigital dysplasia, OMIM:164200;Oculodentodigital dysplasia, autosomal recessive, OMIM:257850 False 3 0;0;0 30.556 False ENSG00000152661 ENSG00000152661 HGNC:4274 GJB1 gene GJB1 Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Charcot-Marie-Tooth neuropathy, X-linked dominant, 1 False 3 0;0;0 30.556 False ENSG00000169562 ENSG00000169562 HGNC:4283 GJC2 gene GJC2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 44, autosomal recessive, 613206;Leukodystrophy, hypomyelinating, 2, 608804;Lymphedema, hereditary, IC, 613480 25655951 False 3 0;0;0 30.556 False ENSG00000198835 ENSG00000198835 HGNC:17494 GJC2 gene GJC2 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 2, OMIM:608804 False 3 100;0;0 30.556 False ENSG00000198835 ENSG00000198835 HGNC:17494 GK gene GK Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Glycerol kinase deficiency 307030 27604308;8651297;9719371;10737976;10736265 False 3 0;0;0 30.556 False ENSG00000198814 ENSG00000198814 HGNC:4289 GK gene GK Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Glycerol kinase deficiency, 307030;GLYCEROL KINASE DEFICIENCY False 3 33;67;0 30.556 False ENSG00000198814 ENSG00000198814 HGNC:4289 GLA gene GLA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Fabry disease, cardiac variant, 301500;Fabry Disease;Fabry disease (Sphingolipidoses);Fabry disease, 301500 27604308 False 3 0;0;0 30.556 False ENSG00000102393 ENSG00000102393 HGNC:4296 GLB1 gene GLB1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MUCOPOLYSACCHARIDOSIS TYPE 4B;MPS IVB, Morquio B disease (MPS IV, Morquio disease);Mucopolysaccharidosis type IVB (Morquio), 253010;GM1-gangliosidosis (Sphingolipidoses);GM1-gangliosidosis, type II, 230600;GM1-gangliosidosis, type III, 230650;Mucopolysaccharidosis, Type IV;Mucopolysaccharidosis Type IVB;GM1-gangliosidosis, type I, 230500 27604308 False 3 0;0;0 30.556 False ENSG00000170266 ENSG00000170266 HGNC:4298 GLB1 gene GLB1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal GM1-gangliosidosis, type I, 230500GM1-gangliosidosis, type II, 230600GM1-gangliosidosis, type III, 230650Mucopolysaccharidosis type IVB (Morquio), 253010;MUCOPOLYSACCHARIDOSIS TYPE 4B (MPS4B) 1928092;1606711;1909089;10737981;10841810;8199591;1907800;8213816 False 3 100;0;0 30.556 False ENSG00000170266 ENSG00000170266 HGNC:4298 GLB1 gene GLB1 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal GM1-gangliosidosis, type I, OMIM:230500;GM1-gangliosidosis, type II, OMIM:230600 25691190 False 3 100;0;0 30.556 False ENSG00000170266 ENSG00000170266 HGNC:4298 GLDC gene GLDC Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycine encephalopathy, 605899;GLDC-RELATED GLYCINE ENCEPHALOPATHY False 3 100;0;0 30.556 False ENSG00000178445 ENSG00000178445 HGNC:4313 GLDC gene GLDC London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycine encephalopathy, 605899 False 3 0;0;0 30.556 False ENSG00000178445 ENSG00000178445 HGNC:4313 GLI2 gene GLI2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Holoprosencephaly-9, 610829;GLI2-RELATED HOLOPROSENCEPHALY False 3 100;0;0 30.556 False ENSG00000074047 ENSG00000074047 HGNC:4318 GLIS3 gene GLIS3 Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Diabetes mellitus, neonatal, with congenital hypothyroidism, 610199 False 3 100;0;0 30.556 False ENSG00000107249 ENSG00000107249 HGNC:28510 GLRA1 gene GLRA1 Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Hyperekplexia, hereditary 1, 149400 False 3 100;0;0 30.556 False ENSG00000145888 ENSG00000145888 HGNC:4326 GLRA2 gene GLRA2 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Intellectual developmental disorder, X-linked syndromic, Pilorge type, OMIM:301076;intellectual developmental disorder, X-linked, syndromic, Pilorge type, MONDO:0024772 20531469;20479760;26370147;28588452;35294868;29057625 False 3 60;0;40 30.556 False ENSG00000101958 ENSG00000101958 HGNC:4327 GLRX5 gene GLRX5 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spasticity, childhood-onset, with hyperglycinemia, OMIM:616859 24334290;30770271 False 3 100;0;0 30.556 False ENSG00000182512 ENSG00000182512 HGNC:20134 GLRX5 gene GLRX5 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of iron homeostasis;Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive, 205950 False 3 100;0;0 30.556 True ENSG00000182512 ENSG00000182512 HGNC:20134 GLRX5 gene GLRX5 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive, 205950;Disorders of iron homeostasis 27604308 False 3 100;0;0 30.556 False ENSG00000182512 ENSG00000182512 HGNC:20134 GLS gene GLS Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412;Developmental and epileptic encephalopathy 71, OMIM:618328;?Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, OMIM:618339 29468182;30970188;30575854;30239721 False 3 67;33;0 30.556 False ENSG00000115419 ENSG00000115419 HGNC:4331 GLUD1 gene GLUD1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Hyperinsulinemic hypoglycemia and hyperammonemia (Urea cycle disorders and inherited hyperammonaemias);Hyperinsulinism-hyperammonemia syndrome, 606762 27604308 False 3 33;0;67 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000148672 ENSG00000148672 HGNC:4335 GLUL gene GLUL Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glutamine deficiency, congenital, OMIM:610015;Developmental and epileptic encephalopathy 116, OMIM:620806;congenital brain dysgenesis due to glutamine synthetase deficiency, MONDO:0012393;developmental and epileptic encephalopathy 116, MONDO:0970945 16267323;21353613;38579670;39985170;41083803 False 3 50;50;0 30.556 False ENSG00000135821 ENSG00000135821 HGNC:4341 GLUL gene GLUL Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glutamine deficiency, congenital 610015 27604308;16267323;21353613 False 3 0;0;0 30.556 False ENSG00000135821 ENSG00000135821 HGNC:4341 GLYCTK gene GLYCTK Victorian Clinical Genetics Services;Expert Review Green;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal D-glyceric aciduria 220120 False 3 100;0;0 30.556 False ENSG00000168237 ENSG00000168237 HGNC:24247 GLYCTK gene GLYCTK London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal D-glyceric aciduria 220120;D-glyceric aciduria (Disorders of serine, glycine or glycerate metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000168237 ENSG00000168237 HGNC:24247 GM2A gene GM2A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal GM2-gangliosidosis, AB variant, 272750;GM2-GANGLIOSIDOSIS TYPE AB (GM2GAB) 8900233;10364519;1915858;8244332;25529582 False 3 100;0;0 30.556 False ENSG00000196743 ENSG00000196743 HGNC:4367 GM2A gene GM2A London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal GM2-gangliosidosis, AB variant, 272750 False 3 0;0;0 30.556 False ENSG00000196743 ENSG00000196743 HGNC:4367 GMPPA gene GMPPA Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal GLYCOSYLATION DISORDER CHARACTERIZED BY INTELLECTUAL DISABILITY AND AUTONOMIC DYSFUNCTION 24035193 False 3 100;0;0 30.556 False ENSG00000144591 ENSG00000144591 HGNC:22923 GMPPA gene GMPPA Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Alacrima, achalasia, and mental retardation syndrome (MIM# 615510) 24035193;28574218 False 3 100;0;0 30.556 False ENSG00000144591 ENSG00000144591 HGNC:22923 GMPPB gene GMPPB Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal "Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 OMIM:615350;muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14 MONDO:0014140;Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 OMIM:615351;muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14 MONDO:0014141;Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 OMIM:615352;autosomal recessive limb-girdle muscular dystrophy type 2T MONDO:0014142" 23768512;26503795;24896178;25529582 False 3 33;0;67 30.556 False ENSG00000173540 ENSG00000173540 HGNC:22932 GMPPB gene GMPPB Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal "Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 OMIM:615350;muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14 MONDO:0014140;Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 OMIM:615351;muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14 MONDO:0014141;Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 OMIM:615352;autosomal recessive limb-girdle muscular dystrophy type 2T MONDO:0014142" False 3 0;0;0 30.556 False ENSG00000173540 ENSG00000173540 HGNC:22932 GNAI1 gene GNAI1 Victorian Clinical Genetics Services;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities, OMIM:619854 25529582;28135719 False 3 100;0;0 30.556 False ENSG00000127955 ENSG00000127955 HGNC:4384 GNAI2 gene GNAI2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Syndromic intellectual disability 31036916;27787898;39298586 False 3 50;50;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000114353 ENSG00000114353 HGNC:4385 GNAO1 gene GNAO1 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted EPILEPTIC ENCEPHALOPATHY;Neurodevelopmental disorder with involuntary movements, 617493;Epileptic encephalopathy, early infantile, 17, 615473 23993195 False 3 33;67;0 30.556 False ENSG00000087258 ENSG00000087258 HGNC:4389 GNAS gene GNAS Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Pseudohypoparathyroidism Ia, OMIM:103580;pseudohypoparathyroidism type 1A, MONDO:0007078;Pseudohypoparathyroidism Ic, OMIM:612462;pseudohypoparathyroidism type 1C, MONDO:0012911;Pseudopseudohypoparathyroidism, OMIM:612463;pseudopseudohypoparathyroidism, MONDO:0012912 False 3 100;0;0 30.556 False ENSG00000087460 ENSG00000087460 HGNC:4392 GNB1 gene GNB1 Victorian Clinical Genetics Services;Expert Review Green;Other Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Mental retardation, autosomal dominant 42 OMIM:616973;intellectual disability, autosomal dominant 42 MONDO:0014855 27108799;28087732 False 3 100;0;0 30.556 False ENSG00000078369 ENSG00000078369 HGNC:4396 GNB2 gene GNB2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with hypotonia and dysmorphic facies, OMIM:619503 31698099;33971351;34183358 False 3 100;0;0 30.556 False ENSG00000172354 ENSG00000172354 HGNC:4398 GNB5 gene GNB5 Expert Review Green;Literature;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder with cardiac arrhythmia, OMIM:617173;Language delay and ADHD/cognitive impairment with or without cardiac arrhythmia, OMIM:617182 27677260;28697420;29368331;30914295;27523599 False 3 100;0;0 30.556 False ENSG00000069966 ENSG00000069966 HGNC:4401 GNE gene GNE London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Sialuria OMIM:269921;sialuria MONDO:0010028;Nonaka myopathy OMIM:605820;GNE myopathy MONDO:0011603 26721333 False 3 0;0;0 30.556 False ENSG00000159921 ENSG00000159921 HGNC:23657 GNMT gene GNMT Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal "Glycine N-methyltransferase deficiency 606664" 27604308;17660255;11810299;14739680 False 3 0;0;0 30.556 False ENSG00000124713 ENSG00000124713 HGNC:4415 GNPAT gene GNPAT London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Rhizomelic chondrodysplasia punctata type 2 (Peroxisomal disorders);Rhizomelic chondrodysplasia punctata, type 2 222765 27604308 False 3 0;0;0 30.556 False ENSG00000116906 ENSG00000116906 HGNC:4416 GNPAT gene GNPAT Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Chondrodysplasia punctata, rhizomelic, type 2, 222765;RHIZOMELIC CHONDRODYSPLASIA PUNCTATA TYPE 2 (RCDP2) False 3 100;0;0 30.556 False ENSG00000116906 ENSG00000116906 HGNC:4416 GNPTAB gene GNPTAB Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MUCOLIPIDOSIS TYPE II (MLII) 16465621;16200072;16116615 False 3 50;50;0 30.556 False ENSG00000111670 ENSG00000111670 HGNC:29670 GNPTAB gene GNPTAB London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mucolipidosis, Type II;Mucolipidosis, Type III Alpha/Beta;Mucolipidosis III alpha/beta;Mucolipidosis II, I-cell disease (Other lysosomal disorders);Mucolipidosis II alpha/beta 27604308 False 3 0;0;0 30.556 False ENSG00000111670 ENSG00000111670 HGNC:29670 GNPTG gene GNPTG London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mucolipidosis III, Pseudo-Hurler polydystrophy (Other lysosomal disorders);mucolipidpsis type III complementation group C;Mucolipidosis, Type III Gamma;Mucolipidosis III gamma 27604308 False 3 0;0;0 30.556 False ENSG00000090581 ENSG00000090581 HGNC:23026 GNPTG gene GNPTG Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MUCOLIPIDOSIS TYPE III COMPLEMENTATION GROUP C (MLIIIC) 19370764;20034096;10712439;19659762 False 3 33;67;0 30.556 False ENSG00000090581 ENSG00000090581 HGNC:23026 GNS gene GNS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mucopolysaccharidosis type IIID, OMIM:252940 27604308 False 3 0;0;0 30.556 False ENSG00000135677 ENSG00000135677 HGNC:4422 GNS gene GNS Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mucopolysaccharidosis type IIID, OMIM:252940 False 3 100;0;0 30.556 False ENSG00000135677 ENSG00000135677 HGNC:4422 GORAB gene GORAB Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Geroderma osteodysplasticum OMIM:231070;geroderma osteodysplastica MONDO:0009271 26000619;18348262;28807865;30631079 False 3 100;0;0 30.556 False ENSG00000120370 ENSG00000120370 HGNC:25676 GPAA1 gene GPAA1 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;Other Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycosylphosphatidylinositol biosynthesis defect 15, 617810;global developmental delay 29100095;24896178 False 3 0;0;0 30.556 False ENSG00000197858 ENSG00000197858 HGNC:4446 GPATCH11 gene GPATCH11 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 39572588 False 3 100;0;0 30.556 False ENSG00000152133 ENSG00000152133 HGNC:26768 GPC3 gene GPC3 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Simpson-Golabi-Behmel syndrome, type 1, 312870Wilms tumor, somatic, 194070;SIMPSON-GOLABI-BEHMEL SYNDROME, TYPE 1 False 3 100;0;0 30.556 False ENSG00000147257 ENSG00000147257 HGNC:4451 GPC4 gene GPC4 NHS GMS;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Keipert syndrome OMIM# 301026 30982611 False 3 100;0;0 30.556 False ENSG00000076716 ENSG00000076716 HGNC:4452 GPD1 gene GPD1 Expert Review Green;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypertriglyceridemia, transient infantile, 614480 24549054;22226083 False 3 0;0;0 30.556 False ENSG00000167588 ENSG00000167588 HGNC:4455 GPHN gene GPHN London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Molybdenum cofactor deficiency C, OMIM:615501;Mo cofactor deficiency, complementation group C (Disorders of molybdenum cofactor metabolism) 27604308;26613940;24561070;25866352;23393157;23275889;11095995;22040219 False 3 100;0;0 30.556 False ENSG00000171723 ENSG00000171723 HGNC:15465 GPIHBP1 gene GPIHBP1 NHS GMS;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperlipoproteinemia, type 1D OMIM:615947;hyperlipoproteinemia, type 1D MONDO:0014412 False 3 100;0;0 30.556 False ENSG00000182851 ENSG00000277494 HGNC:24945 GPT2 gene GPT2 Expert Review;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with microcephaly and spastic paraplegia, OMIM:616281 27601654;28130718;29226631;25758935 False 3 100;0;0 30.556 False ENSG00000166123 ENSG00000166123 HGNC:18062 GRHPR gene GRHPR London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Primary hyperoxaluria type II (Disorders of glyoxylate metabolism);Hyperoxaluria, primary, type II 27604308 False 3 0;0;0 30.556 False ENSG00000137106 ENSG00000137106 HGNC:4570 GRIA1 gene GRIA1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual developmental disorder, autosomal dominant 67, OMIM:619927;?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 28628100;23033978;26350204;24896178;35675825 False 3 60;0;40 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000155511 ENSG00000155511 HGNC:4571 GRIA2 gene GRIA2 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with language impairment and behavioral abnormalities, OMIM:618917;neurodevelopmental disorder with language impairment and behavioral abnormalities, MONDO:0030060 28725178;26350204;24896178;22669415;28630856;31300657;30847515 False 3 60;0;40 30.556 False ENSG00000120251 ENSG00000120251 HGNC:4572 GRIA3 gene GRIA3 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked 94, 300699;MENTAL RETARDATION X-LINKED TYPE 94 (MRX94) False 3 100;0;0 30.556 False ENSG00000125675 ENSG00000125675 HGNC:4573 GRIA4 gene GRIA4 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with or without seizures and gait abnormalities, 617864 29220673 False 3 100;0;0 30.556 False ENSG00000152578 ENSG00000152578 HGNC:4574 GRID2 gene GRID2 Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spinocerebellar ataxia, autosomal recessive 18, 616204 28856174;24078737;23611888;7792064;20395510 False 3 100;0;0 30.556 False ENSG00000152208 ENSG00000152208 HGNC:4576 GRIK2 gene GRIK2 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Mental retardation, autosomal recessive, 6, OMIM:611092;non-syndromic neurodevelopmental disorder (NDD), autosomal dominant 34375587;17847003;25039795 False 3 100;0;0 30.556 False ENSG00000164418 ENSG00000164418 HGNC:4580 GRIN1 gene GRIN1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant OMIM:614254;intellectual disability, autosomal dominant 8 MONDO:0013655;Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive OMIM:617820;neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive MONDO:0060629 28051072;27164704;28228639;21376300;25864721;27164704;23934111 False 3 33;0;67 30.556 False ENSG00000176884 ENSG00000176884 HGNC:4584 GRIN2A gene GRIN2A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Epilepsy with neurodevelopmental defects, 613971;EPILEPSY WITH NEURODEVELOPMENTAL DEFECTS False 3 100;0;0 30.556 False ENSG00000183454 ENSG00000183454 HGNC:4585 GRIN2B gene GRIN2B Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual developmental disorder, autosomal dominant 6, with or without seizures, OMIM:613970;Developmental and epileptic encephalopathy 27, OMIM:616139 20890276;24272827;28377535;35238837;36758276 False 3 100;0;0 30.556 False ENSG00000273079 ENSG00000273079 HGNC:4586 GRIN2D gene GRIN2D Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Epileptic encephalopathy, early infantile, 46, 617162;intellectual disability 27616483;30280376 False 3 100;0;0 30.556 False ENSG00000105464 ENSG00000105464 HGNC:4588 GRM1 gene GRM1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spinocerebellar ataxia, autosomal recessive 13, OMIM:614831 22901947;26308914;31319223;36140834 False 3 100;0;0 30.556 False ENSG00000152822 ENSG00000152822 HGNC:4593 GRM7 gene GRM7 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with seizures, hypotonia, and brain abnormalities, OMIM:618922 32248644;32286009 False 3 100;0;0 30.556 False ENSG00000196277 ENSG00000196277 HGNC:4599 GRN gene GRN Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal "Ceroid lipofuscinosis, neuronal, 11 OMIM:614706;neuronal ceroid lipofuscinosis 11 MONDO:0013866" 22608501;27021778;28000352;28404863;30922528;31855245 False 3 67;33;0 30.556 False ENSG00000030582 ENSG00000030582 HGNC:4601 GSS gene GSS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glutathione synthetase (GSS) deficiency;Glutathione synthetase deficiency 266130;Glutathione synthetase deficiency with 5-oxoprolinuria;Glutathione synthetase deficiency without 5-oxoprolinuria;Pyroglutamic aciduria;5-oxoprolinuria;Hemolytic anemia due to glutathione synthetase deficiency 231900;Glutathione synthetase deficiency (Disorders of the gamma-glutamyl cycle);Fanconi nephropathy 27604308 False 3 100;0;0 30.556 False ENSG00000100983 ENSG00000100983 HGNC:4624 GSTZ1 gene GSTZ1 Expert Review Green;NHS GMS;Eligibility statement prior genetic testing;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal [Maleylacetoacetate isomerase deficiency], OMIM:617596 27876694 False 3 100;0;0 30.556 False ENSG00000100577 ENSG00000100577 HGNC:4643 GTF2E2 gene GTF2E2 Expert Review Green;Literature;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Trichothiodystrophy 6, nonphotosensitive, OMIM:616943 26996949;28973399 False 3 100;0;0 30.556 False ENSG00000197265 ENSG00000197265 HGNC:4651 GTF2H5 gene GTF2H5 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Trichothiodystrophy, complementation group A, 601675;TRICHOTHIODYSTROPHY PHOTOSENSITIVE False 3 100;0;0 30.556 False ENSG00000272047 ENSG00000272047 HGNC:21157 GTF3C3 gene GTF3C3 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizures, OMIM:621201 28940097;28097321;30552426;40040844 False 3 25;75;0 30.556 False ENSG00000119041 ENSG00000119041 HGNC:4666 GTF3C5 gene GTF3C5 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 35503477;38520561 False 3 100;0;0 30.556 False ENSG00000148308 ENSG00000148308 HGNC:4668 GTPBP2 gene GTPBP2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Jaberi-Elahi syndrome, 617988;Global developmental delay;Intellectual disability;Seizures 26675814;29449720;25061210 False 3 100;0;0 30.556 False ENSG00000172432 ENSG00000172432 HGNC:4670 GTPBP3 gene GTPBP3 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 23 616198 False 3 100;0;0 30.556 True ENSG00000130299 ENSG00000130299 HGNC:14880 GTPBP3 gene GTPBP3 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MITOCHONDRIAL TRANSLATION DEFECT ASSOCIATED WITH HYPERTROPHIC CARDIOMYOPATHY, LACTIC ACIDOSIS, AND ENCEPHALOPATHY 25434004 False 3 33;67;0 30.556 False ENSG00000130299 ENSG00000130299 HGNC:14880 GTPBP3 gene GTPBP3 Victorian Clinical Genetics Services;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis and encephalopathy;Combined oxidative phosphorylation deficiency 23 False 3 100;0;0 30.556 True ENSG00000130299 ENSG00000130299 HGNC:14880 GUK1 gene GUK1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 21, OMIM:621071;mitochondrial dna depletion syndrome 21, MONDO:0976132 39230499 False 3 100;0;0 30.556 False ENSG00000143774 ENSG00000143774 HGNC:4693 GUK1 gene GUK1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 21, OMIM:621071;mitochondrial dna depletion syndrome 21, MONDO:0976132 39230499 False 3 100;0;0 30.556 False ENSG00000143774 ENSG00000143774 HGNC:4693 GUSB gene GUSB Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mucopolysaccharidosis VII, 253220;MUCOPOLYSACCHARIDOSIS TYPE 7 (MPS7) False 3 100;0;0 30.556 False ENSG00000169919 ENSG00000169919 HGNC:4696 GUSB gene GUSB London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MUCOPOLYSACCHARIDOSIS TYPE 7;Mucopolysaccharidosis VII, 253220;MPS VII, Sly disease (MPS IV, Morquio disease);Mucopolysaccharidosis Type VII;Mucopolysaccharidosis, Type VII 27604308 False 3 0;0;0 30.556 False ENSG00000169919 ENSG00000169919 HGNC:4696 GYG1 gene GYG1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Glycogen storage disease XV False 3 100;0;0 30.556 False ENSG00000163754 ENSG00000163754 HGNC:4699 GYS1 gene GYS1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycogen storage disease 0, muscle 27604308;21958591;24579562 False 3 100;0;0 30.556 False ENSG00000104812 ENSG00000104812 HGNC:4706 GYS2 gene GYS2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycogen Storage Disease;Glycogen Storage Disease Type 0, Liver;Glycogen Storage Disorders- Liver;Glycogen storage disease type 0a, liver (Glycogen storage disorders);Glycogen storage disease, type 0, 240600;fasting intolerance without enlarged liver 27604308 False 3 0;0;0 30.556 False ENSG00000111713 ENSG00000111713 HGNC:4707 H3F3A gene H3F3A Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental delay;Intellectual disability;Neurodegeneration;Epilepsy;Facial dysmorphism;Congenital anomalies 31942419;33268356;33057194 False 3 100;0;0 30.556 False ENSG00000163041 ENSG00000163041 HGNC:4764 H3F3B gene H3F3B Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental delay;Intellectual disability;Neurodegeneration;Epilepsy;Facial dysmorphism;Congenital anomalies 33268356 False 3 100;0;0 30.556 False ENSG00000132475 ENSG00000132475 HGNC:4765 HAAO gene HAAO Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple congenital malformations;VACTERL-like phenotype 27604308;17334708;28792876 False 3 0;0;0 30.556 False ENSG00000162882 ENSG00000162882 HGNC:4796 HACE1 gene HACE1 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia and psychomotor retardation with or without seizures 616756 26424145;26437029;29423242;31321300;33813722 False 3 100;0;0 30.556 False ENSG00000085382 ENSG00000085382 HGNC:21033 HADH gene HADH Expert Review Green;NHS GMS;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-hydroxyacyl-CoA dehydrogenase deficiency 231530;Hyperinsulinemic hypoglycemia, familial, 4 609975 27604308;11489939;26316438;23430856;23506826;25915078;26316438;27181376 False 3 0;0;100 30.556 False ENSG00000138796 ENSG00000138796 HGNC:4799 HADHA gene HADHA NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial trifunctional protein deficiency (Disorders of mitochondrial fatty acid oxidation);Trifunctional protein deficiency 609015 27604308 False 3 50;0;50 30.556 False ENSG00000084754 ENSG00000084754 HGNC:4801 HADHA gene HADHA Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal LONG CHAIN 3-HYDROXYACYL-COA DEHYDROGENASE DEFICIENCY 7811722 False 3 33;67;0 30.556 False ENSG00000084754 ENSG00000084754 HGNC:4801 HADHB gene HADHB NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial trifunctional protein deficiency (Disorders of mitochondrial fatty acid oxidation);Trifunctional protein deficiency 609015 27604308 False 3 50;0;50 30.556 False ENSG00000138029 ENSG00000138029 HGNC:4803 HADHB gene HADHB Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial trifunctional protein deficiency 2, OMIM:620300 35403730 False 3 100;0;0 30.556 False ENSG00000138029 ENSG00000138029 HGNC:4803 HAMP gene HAMP London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hemochromatosis, type 2B 613313;Hereditary haemochromatosis Type 2 (Disorder of iron metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000105697 ENSG00000105697 HGNC:15598 HARS2 gene HARS2 Expert Review Green;Expert Review Green;Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Multiple respiratory chain complex deficiencies (disorders of protein synthesis);?Perrault syndrome 2 614926;Perrault syndrome 2, 614926 27650058;21464306 False 3 33;33;33 30.556 False ENSG00000112855 ENSG00000112855 HGNC:4817 HARS2 gene HARS2 Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Perrault syndrome 2, 614926 21464306;27650058 False 3 50;50;0 30.556 True ENSG00000112855 ENSG00000112855 HGNC:4817 HCCS gene HCCS Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Microphthalmia, syndromic 7, 309801;Linear skin defects with multiple congenital anomalies 1 False 3 100;0;0 30.556 True ENSG00000004961 ENSG00000004961 HGNC:4837 HCCS gene HCCS NHS GMS;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Microphthalmia, syndromic 7, 309801;MICROPHTHALMIA SYNDROMIC TYPE 7 (MCOPS7) False 3 100;0;0 30.556 False ENSG00000004961 ENSG00000004961 HGNC:4837 HCCS gene HCCS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Linear skin defects with multiple congenital anomalies 1;Complex III (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors);Microphthalmia, syndromic 7, 309801 27604308 False 3 100;0;0 30.556 False ENSG00000004961 ENSG00000004961 HGNC:4837 HCFC1 gene HCFC1 Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked 3, 309541;MENTAL RETARDATION, X-LINKED 3; MRX3 False 3 100;0;0 30.556 False ENSG00000172534 ENSG00000172534 HGNC:4839 HCFC1 gene HCFC1 Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked 3 (methylmalonic acidemia and homocysteinemia, cblX type ) 309541 False 3 100;0;0 30.556 False ENSG00000172534 ENSG00000172534 HGNC:4839 HCN1 gene HCN1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 24; EIEE24 24747641 False 3 33;67;0 30.556 False ENSG00000164588 ENSG00000164588 HGNC:4845 HDAC3 gene HDAC3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 39047730 False 3 100;0;0 30.556 False ENSG00000171720 ENSG00000171720 HGNC:4854 HDAC4 gene HDAC4 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Brachydactyly-mental retardation syndrome, 600430;BRACHYDACTYLY-MENTAL RETARDATION SYNDROME (BDMR) 30848064;24715439;20691407;31209962;25529582;24896178 False 3 80;20;0 30.556 False ENSG00000068024 ENSG00000068024 HGNC:14063 HDAC8 gene HDAC8 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Wilson-Turner syndrome, 309585Cornelia de Lange syndrome 5, 300882;CORNELIA DE LANGE-LIKE SYNDROME False 3 100;0;0 30.556 False ENSG00000147099 ENSG00000147099 HGNC:13315 HECTD4 gene HECTD4 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum, OMIM:620250 36401616 False 3 100;0;0 30.556 False ENSG00000173064 ENSG00000173064 HGNC:26611 HECW2 gene HECW2 Victorian Clinical Genetics Services;BRIDGE study SPEED NEURO Tier1 Gene;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with hypotonia, seizures, and absent language, OMIM:617268 27389779;27334371;34321324 False 3 0;0;0 30.556 False Other ENSG00000138411 ENSG00000138411 HGNC:29853 HEPACAM gene HEPACAM Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Megalencephalic leukoencephalopathy with subcortical cysts 2A, OMIM:613925;Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation, OMIM:613926 25655951 False 3 0;0;0 30.556 False ENSG00000165478 ENSG00000165478 HGNC:26361 HEPACAM gene HEPACAM Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Megalencephalic leukoencephalopathy with subcortical cysts 2A, OMIM:613925;Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation, OMIM:613926 21419380 False 3 100;0;0 30.556 False ENSG00000165478 ENSG00000165478 HGNC:26361 HERC1 gene HERC1 Expert Review Green;Other Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Macrocephaly, dysmorphic facies, and psychomotor retardation 617011 26138117;26153217;27108999 False 3 100;0;0 30.556 False ENSG00000103657 ENSG00000103657 HGNC:4867 HERC2 gene HERC2 Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mental retardation, autosomal recessive 38, OMIM:615516 23065719;23243086;30902390;32571899;27848944;26077850;27759030 False 3 50;50;0 30.556 False ENSG00000128731 ENSG00000128731 HGNC:4868 HESX1 gene HESX1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Growth hormone deficiency with pituitary anomalies, OMIM:182230;Pituitary hormone deficiency, combined, 5, OMIM:182230;Septooptic dysplasia, OMIM:182230 False 3 100;0;0 30.556 False ENSG00000163666 ENSG00000163666 HGNC:4877 HEXA gene HEXA Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Tay-Sachs disease, 272800;GM2-gangliosidosis, several forms, 272800;GM2-GANGLIOSIDOSIS TYPE 1 (GM2G1) False 3 100;0;0 30.556 False ENSG00000213614 ENSG00000213614 HGNC:4878 HEXA gene HEXA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal GM2-gangliosidosis, several forms, 272800;Tay-Sachs disease, 272800 False 3 0;0;0 30.556 False ENSG00000213614 ENSG00000213614 HGNC:4878 HEXB gene HEXB London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sandhoff disease, infantile, juvenile, and adult forms, OMIM:268800 27604308 False 3 0;0;0 30.556 False ENSG00000049860 ENSG00000049860 HGNC:4879 HEXB gene HEXB Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sandhoff disease, infantile, juvenile, and adult forms, OMIM:268800 False 3 100;0;0 30.556 False ENSG00000049860 ENSG00000049860 HGNC:4879 HFE gene HFE London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hemochromatosis, OMIM:235200 27604308 False 3 100;0;0 30.556 False ENSG00000010704 ENSG00000010704 HGNC:4886 HFE2 gene HFE2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hemochromatosis, type 2A, 602390;Hereditary haemochromatosis Type 2 (Disorder of iron metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000168509 ENSG00000168509 HGNC:4887 HGD gene HGD London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Alkaptonuria 27604308 False 3 0;0;0 30.556 False ENSG00000113924 ENSG00000113924 HGNC:4892 HGSNAT gene HGSNAT London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mucopolysaccharidosis Type III;Mucopolysaccharidosis, Type III;Retinitis Pigmentosa 73;Mucopolysaccharidosis type IIIC (Sanfilippo C), 252930;Mucopolysaccharidosis Type IIIC;MPS IIIC, Sanfilippo C disease (Mucopolysaccharidoses) 27604308 False 3 0;0;0 30.556 False ENSG00000165102 ENSG00000165102 HGNC:26527 HGSNAT gene HGSNAT Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MUCOPOLYSACCHARIDOSIS TYPE 3C (MPS3C) 16960811;18518886;18024218;17033958;20825431 False 3 100;0;0 30.556 False ENSG00000165102 ENSG00000165102 HGNC:26527 HIBCH gene HIBCH London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-hydroxyisobutryl-CoA hydrolase deficiency, 250620;HIBCH deficiency;Methacrylic aciduria (Organic acidurias) 27604308 False 3 100;0;0 30.556 False ENSG00000198130 ENSG00000198130 HGNC:4908 HIBCH gene HIBCH Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-hydroxyisobutryl-CoA hydrolase deficiency, 250620;HIBCH deficiency PMID: 25251209;24299452 False 3 100;0;0 30.556 True ENSG00000198130 ENSG00000198130 HGNC:4908 HIBCH gene HIBCH Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal HIBCH DEFICIENCY 7122152 False 3 33;67;0 30.556 False ENSG00000198130 ENSG00000198130 HGNC:4908 HID1 gene HID1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Syndromic infantile encephalopathy;Hypopituitarism;Developmental and epileptic encephalopathy 105 with hypopituitarism, OMIM:619983 33999436 False 3 100;0;0 30.556 False ENSG00000167861 ENSG00000167861 HGNC:15736 HIKESHI gene HIKESHI Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 13, OMIM:616881 26545878;28000699 False 3 100;0;0 30.556 False ENSG00000149196 ENSG00000149196 HGNC:26938 HIST1H1E gene HIST1H1E Victorian Clinical Genetics Services;Expert Review Green;Other Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Rahman syndrome, 617537; mild to severe intellectual disability 28475857;34788807 False 3 0;0;0 30.556 False ENSG00000168298 ENSG00000168298 HGNC:4718 HIST1H4C gene HIST1H4C Expert Review Green;Victorian Clinical Genetics Services;Gene2Phenotype Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Tessadori-van Haaften neurodevelopmental syndrome 1, OMIM:619758 28920961;35202563 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000197061 ENSG00000197061 HGNC:4787 HIST1H4E gene HIST1H4E Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Tessadori-van Haaften neurodevelopmental syndrome 3, OMIM:619950;Tessadori-Van Haaften neurodevelopmental syndrome 3 MONDO:0030993 35202563 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000198518 ENSG00000276966 HGNC:4790 HIVEP2 gene HIVEP2 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Mental retardation, autosomal dominant 43, 616977;MRD43;Intellectual disability 23020937;26153216;27003583;26350204 False 3 33;0;67 30.556 False ENSG00000010818 ENSG00000010818 HGNC:4921 HK1 gene HK1 NHS GMS;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with visual defects and brain anomalies, OMIM:618547 30778173;28135719 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000156515 ENSG00000156515 HGNC:4922 HLCS gene HLCS Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Holocarboxylase synthetase deficiency, 253270;HOLOCARBOXYLASE SYNTHETASE DEFICIENCY False 3 33;67;0 30.556 False ENSG00000159267 ENSG00000159267 HGNC:4976 HLCS gene HLCS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Holocarboxylase synthetase deficiency;Holocarboxylase synthetase deficiency, 253270;lactic acidosis with seizures and eczema, immune deficiency;Holocarboxylase synthetase deficiency (Disorders of biotin metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000159267 ENSG00000159267 HGNC:4976 HLCS gene HLCS Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Holocarboxylase synthetase deficiency, 253270 False 3 100;0;0 30.556 True ENSG00000159267 ENSG00000159267 HGNC:4976 HMBS gene HMBS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Porphyria, acute intermittent OMIM:176000;acute intermittent porphyria MONDO:0008294;Leukoencephalopathy, porphyria-related OMIM:620711;leukoencephalopathy, porphyria-related, MONDO:0958226;Encephalopathy, porphyria-related, OMIM:620704;encephalopathy, porphyria-related, MONDO:0958224 27604308;38940544;27539938;14262853;1577472;15534187;14970743;27558376;31153822;34089223;2511016;1714233 False 3 100;0;0 30.556 False ENSG00000256269 ENSG00000256269 HGNC:4982 HMBS gene HMBS Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukoencephalopathy, HP:0002352 27558376;34089223;15534187;31153822 False 3 100;0;0 30.556 False ENSG00000256269 ENSG00000256269 HGNC:4982 HMGB1 gene HMGB1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental delay and microcephaly 34164801 False 3 100;0;0 30.556 False ENSG00000189403 ENSG00000189403 HGNC:4983 HMGCL gene HMGCL Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal HMG-CoA lyase deficiency, 246450;3-Hydroxy-3-methylglutaryl-CoA lyase deficiency;HMGCLD;Intellectual disability 28583327;8617516;9463337;11129331 False 3 50;50;0 30.556 False ENSG00000117305 ENSG00000117305 HGNC:5005 HMGCL gene HMGCL London North GLH;NHS GMS;Expert Review Green;Other Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-Hydroxy-3-methyl glutaric aciduria (Organic acidurias);3-Hydroxy-3-methylglutaryl-CoA lyase deficiency;HMG-CoA lyase deficiency, 246450;HMGCLD 27604308 False 3 67;0;33 30.556 False ENSG00000117305 ENSG00000117305 HGNC:5005 HMGCS2 gene HMGCS2 NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal HMG-CoA synthase-2 deficiency 27604308 False 3 0;0;100 30.556 False ENSG00000134240 ENSG00000134240 HGNC:5008 HNMT gene HNMT Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mental retardation, autosomal recessive 51, OMIM:616739 26206890;30744146;33310825;33739554 False 3 75;25;0 30.556 False ENSG00000150540 ENSG00000150540 HGNC:5028 HNRNPC gene HNRNPC Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual developmental disorder, autosomal dominant 74, OMIM:620688 37541189;40004505 False 3 100;0;0 30.556 False ENSG00000092199 ENSG00000092199 HGNC:5035 HNRNPH1 gene HNRNPH1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted HNRNPH1 related syndromic intellectual disability;Neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects, OMIM:620083 32335897;29938792 False 3 100;0;0 30.556 False ENSG00000169045 ENSG00000169045 HGNC:5041 HNRNPH2 gene HNRNPH2 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Mental retardation, X-linked, syndromic, Bain type, 300986;MRXSB 27545675 False 3 100;0;0 30.556 False ENSG00000126945 ENSG00000126945 HGNC:5042 HNRNPK gene HNRNPK Victorian Clinical Genetics Services;Expert Review Green;Other Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Au-Kline syndrome, 616580;intellectual disability 26173930;26954065;28771707;26638989;28374925;29904177 False 3 100;0;0 30.556 False ENSG00000165119 ENSG00000165119 HGNC:5044 HNRNPR gene HNRNPR Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Global developmental delay;Intellectual disability;Seizures;Postnatal microcephaly;Short digit;Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities, OMIM:620073 31079900;26795593 False 3 100;0;0 30.556 False ENSG00000125944 ENSG00000125944 HGNC:5047 HNRNPU gene HNRNPU Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental and epileptic encephalopathy 54, OMIM:617391 25529582;24896178;23934111;23708187;27652284 False 3 100;0;0 30.556 False ENSG00000153187 ENSG00000153187 HGNC:5048 HOGA1 gene HOGA1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperoxaluria Type III (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Hyperoxaluria, primary, type III 613616 27604308 False 3 0;0;0 30.556 False ENSG00000241935 ENSG00000241935 HGNC:25155 HOXA1 gene HOXA1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Bosley-Salih-Alorainy syndrome, 601536Athabaskan brainstem dysgenesis syndrome, 601536;BOSLEY-SALIH-ALORAINY SYNDROME (BSAS) False 3 100;0;0 30.556 False ENSG00000105991 ENSG00000105991 HGNC:5099 HPD gene HPD Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Tyrosinemia, type III, 276710Hawkinsinuria, 140350;HAWKINSINURIA (HAWK) False 3 100;0;0 30.556 False ENSG00000158104 ENSG00000158104 HGNC:5147 HPD gene HPD Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal "Hawkinsinuria 140350;Tyrosinemia, type III 276710" 27604308;10942115;11073718;26226126;30984715;17560158 False 3 0;0;0 30.556 False ENSG00000158104 ENSG00000158104 HGNC:5147 HPDL gene HPDL Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities OMIM:619026;Spastic paraplegia 83, autosomal recessive OMIM:619027 32707086 False 3 100;0;0 30.556 False ENSG00000186603 ENSG00000186603 HGNC:28242 HPDL gene HPDL Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities OMIM:619026;Spastic paraplegia 83, autosomal recessive OMIM:619027 32707086 False 3 100;0;0 30.556 False ENSG00000186603 ENSG00000186603 HGNC:28242 HPDL gene HPDL Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026;Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613 32707086;33188300 False 3 100;0;0 30.556 False ENSG00000186603 ENSG00000186603 HGNC:28242 HPDL gene HPDL Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026;Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613 32707086;33188300 False 3 100;0;0 30.556 False ENSG00000186603 ENSG00000186603 HGNC:28242 HPRT1 gene HPRT1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Hyperuricemia, HRPT-related, OMIM:300323;Lesch-Nyhan syndrome, OMIM:300322 27604308 False 3 0;0;0 30.556 False ENSG00000165704 ENSG00000165704 HGNC:5157 HPRT1 gene HPRT1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Lesch-Nyhan syndrome, OMIM:300322 False 3 100;0;0 30.556 False ENSG00000165704 ENSG00000165704 HGNC:5157 HPS1 gene HPS1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hermansky-Pudlak syndrome 1 203300 27604308;8896559;9562579;9705234;10971344 False 3 0;0;0 30.556 False ENSG00000107521 ENSG00000107521 HGNC:5163 HRAS gene HRAS Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted {Bladder cancer, somatic}, 109800Costello syndrome, 218040{Thyroid carcinoma, follicular, somatic}, 188470Congenital myopathy with excess of muscle spindles, 218040{Nevus sebaceous, somatic}, 162900Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic, 163200;COSTELLO SYNDROME False 3 100;0;0 30.556 False ENSG00000174775 ENSG00000174775 HGNC:5173 HS2ST1 gene HS2ST1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;dysmorphic features;congenital anomalies 33159882 False 3 0;100;0 30.556 False ENSG00000153936 ENSG00000153936 HGNC:5193 HSD11B2 gene HSD11B2 Expert Review Green;NHS GMS;ClinGen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Apparent mineralocorticoid excess, OMIM:218030;apparent mineralocorticoid excess, MONDO:0009025 7670488;7608290;9683587;17314322 False 3 100;0;0 30.556 False ENSG00000176387 ENSG00000176387 HGNC:5209 HSD17B10 gene HSD17B10 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) HSD10 mitochondrial disease, OMIM:300438 26950678;12696021;19706438;22132097 False 3 100;0;0 30.556 False ENSG00000072506 ENSG00000072506 HGNC:4800 HSD17B10 gene HSD17B10 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) HSD10 mitochondrial disease, OMIM:300438 26950678;12696021;19706438;22132097;16148061;12555940;25529582;24896178 False 3 100;0;0 30.556 False ENSG00000072506 ENSG00000072506 HGNC:4800 HSD17B10 gene HSD17B10 Expert Review Green;London North GLH;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) HSD10 mitochondrial disease, OMIM:300438 19706438;22132097;12696021;26950678;27604308 False 3 100;0;0 30.556 False ENSG00000072506 ENSG00000072506 HGNC:4800 HSD17B4 gene HSD17B4 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal PERRAULT SYNDROME 9345094;9482850;11992265;2921319;10400999;11743515 False 3 33;67;0 30.556 False ENSG00000133835 ENSG00000133835 HGNC:5213 HSD17B4 gene HSD17B4 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome-Associated Disorders & Zellweger Syndrome;General Leukodystrophy & Mitochondrial Leukoencephalopathy;D-bifunctional protein deficiency 25655951 False 3 0;0;0 30.556 False ENSG00000133835 ENSG00000133835 HGNC:5213 HSD17B4 gene HSD17B4 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal D-bifunctional protein deficiency, 261515;Peroxisomal D-bifunctional protein deficiency (Disorders of peroxisomal alpha-, beta and omega-oxidation) 27604308 False 3 0;0;0 30.556 False ENSG00000133835 ENSG00000133835 HGNC:5213 HSD3B7 gene HSD3B7 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3- ?-hydroxysterol ?5-oxidoreductase/isomerase deficiency (Disorders of bile acid biosynthesis);Bile acid synthesis defect, congenital, 1, 607765 27604308 False 3 100;0;0 30.556 False ENSG00000099377 ENSG00000099377 HGNC:18324 HSPA9 gene HSPA9 NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Even-plus syndrome, OMIM:616854 26598328;32869452;35779070;36052765 False 3 100;0;0 30.556 False ENSG00000113013 ENSG00000113013 HGNC:5244 HSPA9 gene HSPA9 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Even-plus syndrome, OMIM:616854;Anemia, sideroblastic, 4, OMIM:182170 26491070;26598328;32869452;35779070;36052765 False 3 100;0;0 30.556 False ENSG00000113013 ENSG00000113013 HGNC:5244 HSPD1 gene HSPD1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 4, OMIM:612233 (AR);Spastic paraplegia 13, autosomal dominant, OMIM:605280 (AD) False 3 100;0;0 30.556 True ENSG00000144381 ENSG00000144381 HGNC:5261 HSPD1 gene HSPD1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 4, OMIM:612233 18571143;27405012;32532876;28377887 False 3 100;0;0 30.556 False ENSG00000144381 ENSG00000144381 HGNC:5261 HSPD1 gene HSPD1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 4, OMIM:612233 (AR);Spastic paraplegia 13, autosomal dominant, OMIM:605280 (AD) 27604308 False 3 100;0;0 30.556 False ENSG00000144381 ENSG00000144381 HGNC:5261 HSPD1 gene HSPD1 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 4, OMIM:612233 18571143;27405012 False 3 100;0;0 30.556 False ENSG00000144381 ENSG00000144381 HGNC:5261 HTRA2 gene HTRA2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-methylglutaconic aciduria, type VIII 617248 27208207;27696117 False 3 100;0;0 30.556 False ENSG00000115317 ENSG00000115317 HGNC:14348 HTRA2 gene HTRA2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal "3-methylglutaconic aciduria, type VIII 617248" 27208207; 27696117 False 3 100;0;0 30.556 False ENSG00000115317 ENSG00000115317 HGNC:14348 HTRA2 gene HTRA2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal " 3-methylglutaconic aciduria, type VIII 617248" 27208207; 27696117 False 3 100;0;0 30.556 False ENSG00000115317 ENSG00000115317 HGNC:14348 HUWE1 gene HUWE1 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 7943042;18252223;24896178;25529582;29180823 False 3 100;0;0 30.556 False ENSG00000086758 ENSG00000086758 HGNC:30892 HYAL1 gene HYAL1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Mucopolysaccharidosis type IX, 601492;MPS IX, Natowicz (MPS IV, Morquio disease) 27604308 False 3 100;0;0 30.556 False ENSG00000114378 ENSG00000114378 HGNC:5320 IARS gene IARS Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, 617093 27426735 False 3 100;0;0 30.556 False ENSG00000196305 ENSG00000196305 HGNC:5330 IARS2 gene IARS2 Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia 616007 30041933;28328135;25130867;27078007 False 3 100;0;0 30.556 False ENSG00000067704 ENSG00000067704 HGNC:29685 IARS2 gene IARS2 Expert Review Green;London North GLH;NHS GMS;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal CAGSSS - Cataracts (CA), growth hormone deficiency (G), sensory neuropathy (S), sensorineural hearing loss (S), and skeletal dysplasia (S);Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only));No OMIM phenotype PMID: 25130867 (3 related cases with CAGSSS homozygous for a rare nonsynonymous variant in this gene, an unrelated case with Leigh syndrome compound heterozygous for variants within this gene);PMID: 27078007 (full text not available to confirm findings). False 3 100;0;0 30.556 False ENSG00000067704 ENSG00000067704 HGNC:29685 IBA57 gene IBA57 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 3, OMIM:615330 28671726;23462291;25971455;28913435;27785568 False 3 100;0;0 30.556 False ENSG00000181873 ENSG00000181873 HGNC:27302 IBA57 gene IBA57 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 3, OMIM:615330 28913435;23462291;25971455;27785568;28671726 False 3 0;0;0 30.556 False ENSG00000181873 ENSG00000181873 HGNC:27302 IBA57 gene IBA57 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 3, OMIM:615330;?Spastic paraplegia 74, autosomal recessive, OMIM:616451 23462291;25971455 False 3 100;0;0 30.556 False ENSG00000181873 ENSG00000181873 HGNC:27302 IBA57 gene IBA57 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 3, OMIM:615330;?Spastic paraplegia 74, autosomal recessive, OMIM:616451 PMID: 23462291;25971455 False 3 100;0;0 30.556 True ENSG00000181873 ENSG00000181873 HGNC:27302 IDH2 gene IDH2 Expert Review Green;Expert Review Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown "D-2-hydroxyglutaric aciduria 2 613657" 20847235;24049096 False 3 0;0;0 30.556 False ENSG00000182054 ENSG00000182054 HGNC:5383 IDH2 gene IDH2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Mitochondrial isocitrate dehydrogenase deficiency (Organic acidurias);D-2-hydroxyglutaric aciduria 2, 613657 24049096;20847235 False 3 100;0;0 30.556 False ENSG00000182054 ENSG00000182054 HGNC:5383 IDH3A gene IDH3A Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Retinitis pigmentosa 90, OMIM:619007;retinitis pigmentosa 90, MONDO:0033563 31012789;30478029;30058936;28412069;28058510 False 3 100;0;0 30.556 False ENSG00000166411 ENSG00000166411 HGNC:5384 IDH3A gene IDH3A Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Retinitis pigmentosa 90, OMIM:619007;retinitis pigmentosa 90, MONDO:0033563 31012789;30478029;30058936;28412069;28058510 False 3 100;0;0 30.556 False ENSG00000166411 ENSG00000166411 HGNC:5384 IDS gene IDS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females MUCOPOLYSACCHARIDOSIS TYPE 2;MPS II, Hunter disease (Mucopolysaccharidoses);Mucopolysaccharidosis II, 309900;Mucopolysaccharidosis Type II 27604308 False 3 0;0;0 30.556 False ENSG00000010404 ENSG00000010404 HGNC:5389 IDS gene IDS Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mucopolysaccharidosis II, 309900;MUCOPOLYSACCHARIDOSIS TYPE 2 (MPS2) False 3 100;0;0 30.556 False ENSG00000010404 ENSG00000010404 HGNC:5389 IDUA gene IDUA Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mucopolysaccharidosis Ih, 607014Mucopolysaccharidosis Is, 607016Mucopolysaccharidosis Ih/s, 607015;MUCOPOLYSACCHARIDOSIS TYPE 1S (MPS1S) False 3 100;0;0 30.556 False ENSG00000127415 ENSG00000127415 HGNC:5391 IDUA gene IDUA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hurler syndrome;Mucopolysaccharidosis type 1H/S;MPS I, Hurler, Scheie disease (Mucopolysaccharidoses);Scheie syndrome;Hurler-Scheie syndrome;Mucopolysaccharidosis type 1S;Mucopolysaccharidosis type 1H;Mucopolysaccharidosis Ih/s, 607015;Mucopolysaccharidosis, Type I;Mucopolysaccharidosis Is, 607016;Mucopolysaccharidosis Ih, 607014 27604308 False 3 0;0;0 30.556 False ENSG00000127415 ENSG00000127415 HGNC:5391 IER3IP1 gene IER3IP1 Expert Review Green;Expert Review Green;Other Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly, epilepsy, and diabetes syndrome, 614231;MEDS 24138066;22991235;21835305 False 3 67;0;33 30.556 False ENSG00000134049 ENSG00000134049 HGNC:18550 IER3IP1 gene IER3IP1 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly, epilepsy, and diabetes syndrome, 614231; MEDS; Intellectual disability 21835305;22991235;24138066 False 3 50;0;50 30.556 False ENSG00000134049 ENSG00000134049 HGNC:18550 IFIH1 gene IFIH1 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Aicardi-Goutieres syndrome 7, OMIM:615846 24995871;24686847;25604658 False 3 0;0;0 30.556 False ENSG00000115267 ENSG00000115267 HGNC:18873 IFIH1 gene IFIH1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Aicardi-Goutieres syndrome 7, OMIM:615846 24995871 False 3 33;67;0 30.556 False ENSG00000115267 ENSG00000115267 HGNC:18873 IFT172 gene IFT172 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MAINZER-SALDINO SYNDROME 24140113 False 3 33;67;0 30.556 False ENSG00000138002 ENSG00000138002 HGNC:30391 IGF1 gene IGF1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Insulin-like growth factor I deficiency, OMIM:608747 False 3 100;0;0 30.556 False ENSG00000017427 ENSG00000017427 HGNC:5464 IGF1R gene IGF1R Victorian Clinical Genetics Services;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Insulin-like growth factor I, resistance to, OMIM:270450 25529582;26252249;22130793;14657428;23045302 False 3 67;33;0 30.556 False ENSG00000140443 ENSG00000140443 HGNC:5465 IKBKG gene IKBKG Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Incontinentia pigmenti, OMIM:308300 False 3 33;67;0 30.556 False ENSG00000073009 ENSG00000269335 HGNC:5961 IL1RAPL1 gene IL1RAPL1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental Retardation, X-linked;Mental retardation, X-linked 21/34, 300143;MENTAL RETARDATION X-LINKED TYPE 21 (MRX21) False 3 100;0;0 30.556 False ENSG00000169306 ENSG00000169306 HGNC:5996 IMPDH2 gene IMPDH2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with dystonia 33098801 False 3 100;0;0 30.556 False ENSG00000178035 ENSG00000178035 HGNC:6053 INPP4A gene INPP4A Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 21937992;31978615;31938306;25338135;20011524;36653678;39315527;40748307;40772914 False 3 33;17;50 30.556 False ENSG00000040933 ENSG00000040933 HGNC:6074 INPP5E gene INPP5E Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mental retardation, truncal obesity, retinal dystrophy, and micropenis, 610156;Joubert syndrome 1, 213300;MENTAL RETARDATION-TRUNCAL OBESITY-RETINAL DYSTROPHY-MICROPENIS (MORMS) 26748598;25529582;24896178;19668216 False 3 100;0;0 30.556 False ENSG00000148384 ENSG00000148384 HGNC:21474 INPP5K gene INPP5K Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital Muscular Dystrophy Overlapping Marinesco-Sjogren Syndrome and Dystroglycanopathy; Congenital Muscular Dystrophy with Cataracts and Mild Cognitive Impairment 28190459; 28190456 False 3 100;0;0 30.556 False ENSG00000132376 ENSG00000132376 HGNC:33882 INTS1 gene INTS1 Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies, OMIM:618571 28542170;30622326;17544522;31428919 False 3 50;50;0 30.556 False ENSG00000164880 ENSG00000164880 HGNC:24555 INTS11 gene INTS11 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, OMIM:620428 37054711 False 3 100;0;0 30.556 False ENSG00000127054 ENSG00000127054 HGNC:26052 IQSEC2 gene IQSEC2 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Expert Review;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Intellectual developmental disorder, X-linked 1, OMIM:309530 20473311;23674175;30842726;31415821;33368194 False 3 100;0;0 30.556 False ENSG00000124313 ENSG00000124313 HGNC:29059 IREB2 gene IREB2 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia, OMIM:618451 11175792;30915432;31243445;35602653 False 3 100;0;0 30.556 False ENSG00000136381 ENSG00000136381 HGNC:6115 IRF2BPL gene IRF2BPL Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures OMIM:618088;neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures MONDO:0060759 30057031;28135719;25363768;30166628 False 3 100;0;0 30.556 False ENSG00000119669 ENSG00000119669 HGNC:14282 IRX5 gene IRX5 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal HYPERTELORISM, SEVERE, WITH MIDFACE PROMINENCE, MYOPIA, MENTAL RETARDATION, AND BONE FRAGILITY 0 False 3 100;0;0 30.556 False ENSG00000176842 ENSG00000176842 HGNC:14361 ISCA1 gene ISCA1 Expert Review Green;Expert Review;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 5, 617613 28356563;29767723 False 3 0;0;0 30.556 False ENSG00000135070 ENSG00000135070 HGNC:28660 ISCA1 gene ISCA1 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 5, OMIM:617613 28356563;32092383;31016283;30113620;30105122 False 3 100;0;0 30.556 False ENSG00000135070 ENSG00000135070 HGNC:28660 ISCA1 gene ISCA1 Expert Review Green;Expert Review Green;Expert Review;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 5, 617613 29767723;28356563 False 3 0;0;0 30.556 False ENSG00000135070 ENSG00000135070 HGNC:28660 ISCA2 gene ISCA2 Expert Review Green;Victorian Clinical Genetics Services;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal infantile neurodegenerative mitochondrial disorder 25539947;29297947;29359243 False 3 100;0;0 30.556 False ENSG00000165898 ENSG00000165898 HGNC:19857 ISCA2 gene ISCA2 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 4, OMIM:616370 25558065;22323289;25539947;27564080 False 3 100;0;0 30.556 False ENSG00000165898 ENSG00000165898 HGNC:19857 ISCA2 gene ISCA2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 4 616370 25539947;29359243 False 3 100;0;0 30.556 False ENSG00000165898 ENSG00000165898 HGNC:19857 ISCU gene ISCU Expert Review Green;Expert Review Green;London North GLH;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Myopathy with lactic acidosis, hereditary, 255125;Disorders of iron homeostasis;Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Rhabdomyolysis and metabolic muscle disorders 18304497;29079705;18296749;19567699;20206689;21165651;22125086 False 3 100;0;0 30.556 False ENSG00000136003 ENSG00000136003 HGNC:29882 ISCU gene ISCU Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Disorders of iron homeostasis;Myopathy with lactic acidosis, hereditary, 255125 18296749;29079705;19567699;20206689;18304497 False 3 100;0;0 30.556 False ENSG00000136003 ENSG00000136003 HGNC:29882 ISPD gene ISPD Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 26404900;26687144 False 3 0;0;0 30.556 False ENSG00000214960 ENSG00000214960 HGNC:37276 ISPD gene ISPD Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, 614643;WALKER WARBURG SYNDROME False 3 100;0;0 30.556 False ENSG00000214960 ENSG00000214960 HGNC:37276 ITPA gene ITPA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Inosine triphosphatase deficiency (Disorders of purine metabolism);Epileptic encephalopathy, early infantile, 35, 616647;[Inosine triphosphatase deficiency], 613850 27604308 False 3 100;0;0 30.556 False ENSG00000125877 ENSG00000125877 HGNC:6176 ITPA gene ITPA Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epileptic encephalopathy, early infantile, 35, 616647 26224535;30816001;19498443 False 3 100;0;0 30.556 False ENSG00000125877 ENSG00000125877 HGNC:6176 ITPR1 gene ITPR1 NHS GMS;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Gillespie syndrome, OMIM:206700;Spinocerebellar ataxia 15, OMIM:606658;Spinocerebellar ataxia 29, congenital nonprogressive, OMIM:117360 22986007;29925855;27108797 False 3 40;60;0 30.556 False ENSG00000150995 ENSG00000150995 HGNC:6180 ITSN1 gene ITSN1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 34707297 False 3 100;0;0 30.556 False ENSG00000205726 ENSG00000205726 HGNC:6183 IVD gene IVD Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ISOVALERIC ACIDEMIA 2063866;15486829;10677295;1310317 False 3 33;67;0 30.556 False ENSG00000128928 ENSG00000128928 HGNC:6186 IVD gene IVD London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections.;Isovaleric acidemia;Isovaleric aciduria (Organic acidurias) 27604308;24816252 False 3 0;0;0 30.556 False ENSG00000128928 ENSG00000128928 HGNC:6186 JAM3 gene JAM3 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, 613730;HEMORRHAGIC DESTRUCTION OF THE BRAIN, SUBEPENDYMAL CALCIFICATION, AND CATARACTS False 3 100;0;0 30.556 False ENSG00000166086 ENSG00000166086 HGNC:15532 JAM3 gene JAM3 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, 613730 False 3 0;0;0 30.556 False ENSG00000166086 ENSG00000166086 HGNC:15532 JARID2 gene JARID2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual disability;Neurodevelopmental syndrome;Developmental delay with variable intellectual disability and dysmorphic facies, OMIM:620098 23294540;33077894 False 3 100;0;0 30.556 False ENSG00000008083 ENSG00000008083 HGNC:6196 KANSL1 gene KANSL1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Koolen-De Vries syndrome, 610443;Intellectual Disability Syndrome;CHROMOSOME 17Q21.31 MICRODELETION SYNDROME False 3 100;0;0 30.556 False ENSG00000120071 ENSG00000120071 HGNC:24565 KARS gene KARS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Deafness, autosomal recessive 89, 613916;Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Charcot-Marie-Tooth disease, recessive intermediate, B (Lysyl-tRNA synthetase mutations) (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Charcot-Marie-Tooth disease, recessive intermediate, B, 613641 27604308 False 3 100;0;0 30.556 False ENSG00000065427 ENSG00000065427 HGNC:6215 KARS gene KARS Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Global developmental delay;Intellectual disability;Seizures;?Charcot-Marie-Tooth disease, recessive intermediate, B, 613641;Deafness, autosomal recessive 89, 613916 29615062;30252186;28496994;28887846;25330800 False 3 100;0;0 30.556 False ENSG00000065427 ENSG00000065427 HGNC:6215 KARS gene KARS Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Charcot-Marie-Tooth disease, recessive intermediate, B, 613641;Deafness, autosomal recessive 89, 613916 28887846;25330800;29615062;30252186;28496994 False 3 100;0;0 30.556 True ENSG00000065427 ENSG00000065427 HGNC:6215 KAT5 gene KAT5 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Severe global developmental delay;Intellectual disability;Seizures;Microcephaly;Behavioral abnormality;Sleep disturbance;Morphological abnormality of the central nervous system;Short stature;Oral cleft;Abnormality of the face 32822602 False 3 100;0;0 30.556 False ENSG00000172977 ENSG00000172977 HGNC:5275 KAT6A gene KAT6A Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted MENTAL RETARDATION, AUTOSOMAL DOMINANT 32 25728775 False 3 100;0;0 30.556 False ENSG00000083168 ENSG00000083168 HGNC:13013 KAT6B gene KAT6B Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted SBBYSS syndrome, 603736Genitopatellar syndrome, 606170;BLEPHAROPHIMOSIS/INTELLECTUAL DISABILITY PHENOTYPE WHICH IS NOONAN-LIKE False 3 100;0;0 30.556 False ENSG00000156650 ENSG00000156650 HGNC:17582 KAT8 gene KAT8 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Li-Ghorgani-Weisz-Hubshman syndrome, OMIM:618974;Global developmental delay;Intellectual disability;Seizures;Abnormality of vision;Feeding difficulties;Abnormality of the cardiovascular system;Autism 31794431 False 3 100;0;0 30.556 False Other ENSG00000103510 ENSG00000103510 HGNC:17933 KCNA2 gene KCNA2 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted EPILEPTIC ENCEPHALOPATHY. 25751627 False 3 33;67;0 30.556 False ENSG00000177301 ENSG00000177301 HGNC:6220 KCNA3 gene KCNA3 Expert Review Green;NHS GMS;Expert Review Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 37964487 False 3 100;0;0 30.556 False ENSG00000177272 ENSG00000177272 HGNC:6221 KCNB1 gene KCNB1 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 26 25164438 False 3 33;67;0 30.556 False ENSG00000158445 ENSG00000158445 HGNC:6231 KCNB2 gene KCNB2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 38503299 False 3 100;0;0 30.556 False ENSG00000182674 ENSG00000182674 HGNC:6232 KCNC1 gene KCNC1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted EPILEPSY, PROGRESSIVE MYOCLONIC 7 25401298;28145425 False 3 33;67;0 30.556 False ENSG00000129159 ENSG00000129159 HGNC:6233 KCND2 gene KCND2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown global developmental delay, HP:0001263 34245260;16934482;24501278 False 3 0;0;0 30.556 False Other ENSG00000184408 ENSG00000184408 HGNC:6238 KCNH1 gene KCNH1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Temple-Baraitser syndrome, OMIM:611816;Zimmermann-Laband syndrome 1, OMIM:135500;Intellectual disability;Encephalopathy without features of TBS/ZLS 25420144;33594261;33811134 False 3 100;0;0 30.556 False ENSG00000143473 ENSG00000143473 HGNC:6250 KCNH5 gene KCNH5 NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental and epileptic encephalopathy 112, OMIM:620537 23647072;35874597;36307226;24133262 False 3 50;0;50 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000140015 ENSG00000140015 HGNC:6254 KCNJ10 gene KCNJ10 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Illumina TruGenome Clinical Sequencing Services;UKGTN Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Seizures, Sensorineural Deafness, Ataxia, Mental Retardation, andElectrolyte Imbalance Syndrome;SESAME syndrome, 612780Enlarged vestibular aqueduct, digenic, 600791;SEIZURES-SENSORINEURAL DEAFNESS-ATAXIA-MENTAL RETARDATION-ELECTROLYTE IMBALANCE (SESAME) False 3 100;0;0 30.556 False ENSG00000177807 ENSG00000177807 HGNC:6256 KCNJ11 gene KCNJ11 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Hyperinsulinemic hypoglycemia, familial, 2, 601820Diabetes, permanent neonatal, 606176Diabetes mellitus, permanent neonatal, with neurologic features, 606176{Diabetes mellitus, type 2, susceptibility to}, 125853Diabetes mellitus, transient neonatal, 3, 610582;FAMILIAL HYPERINSULINISM 25678012;16670688;27681997;28943513;25529582;24896178 False 3 100;0;0 30.556 False ENSG00000187486 ENSG00000187486 HGNC:6257 KCNJ6 gene KCNJ6 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Keppen-Lubinsky syndrome 614098 25620207 False 3 33;67;0 30.556 False ENSG00000157542 ENSG00000157542 HGNC:6267 KCNK3 gene KCNK3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Developmental disorder with sleep apnea 36195757 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000171303 ENSG00000171303 HGNC:6278 KCNK9 gene KCNK9 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) Birk-Barel mental retardation dysmorphism syndrome 612292 28333430; 27151206 ; 24980697; 18678320 False 3 33;0;67 30.556 False Other - please provide details in the comments ENSG00000169427 ENSG00000169427 HGNC:6283 KCNMA1 gene KCNMA1 Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Cerebellar atrophy, developmental delay, and seizures, OMIM:617643;Cerebellar atrophy, developmental delay, and seizures, MONDO:0060551;Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, OMIM:609446;Generalized epilepsy-paroxysmal dyskinesia syndrome, MONDO:0012276;Liang-Wang syndrome, OMIM:618729;Liang-Wang syndrome, MONDO:0032886;{Epilepsy, idiopathic generalized, susceptibility to, 16}, OMIM:618596;Epilepsy, idiopathic generalized, susceptibility to, 16, MONDO:0032827 15937479;26195193;27567911;29330545;29545233;31152168;31427379 False 3 29;29;43 30.556 False ENSG00000156113 ENSG00000156113 HGNC:6284 KCNN2 gene KCNN2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual disability;seizures;movement disorder 33242881 False 3 100;0;0 30.556 False ENSG00000080709 ENSG00000080709 HGNC:6291 KCNN3 gene KCNN3 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Zimmermann-Laband syndrome 3, OMIM:618658 31155282;33594261 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000143603 ENSG00000143603 HGNC:6292 KCNQ2 gene KCNQ2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental and epileptic encephalopathy 7, OMIM:613720 10323247;17872363;15249611;9430594;9425895;11175290;11572947;16235065;33811133 False 3 100;0;0 30.556 False ENSG00000075043 ENSG00000075043 HGNC:6296 KCNQ3 gene KCNQ3 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown 25524373;20384724;25982755;28135719 False 3 50;0;50 30.556 False ENSG00000184156 ENSG00000184156 HGNC:6297 KCNQ5 gene KCNQ5 Victorian Clinical Genetics Services;Expert Review Green;Literature;Other Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Mental retardation, autosomal dominant 46, 617601;intellectual disability 28669405 False 3 67;33;0 30.556 False ENSG00000185760 ENSG00000185760 HGNC:6299 KCNT1 gene KCNT1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Epileptic encephalopathy, early infantile, 14, 614959Epilepsy, nocturnal frontal lobe, 5, 615005;MALIGNANT MIGRATING PARTIAL SEIZURES OF INFANCY False 3 100;0;0 30.556 False ENSG00000107147 ENSG00000107147 HGNC:18865 KCNT2 gene KCNT2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Developmental and epileptic encephalopathy 57, OMIM:617771;developmental and epileptic encephalopathy, 57, MONDO:0033366 29069600;29740868;37062836 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000162687 ENSG00000162687 HGNC:18866 KCTD3 gene KCTD3 Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epilepsy and global developmental delay 29406573;27848944;25558065 False 3 100;0;0 30.556 False ENSG00000136636 ENSG00000136636 HGNC:21305 KCTD7 gene KCTD7 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epilepsy, progressive myoclonic 3, with or without intracellular inclusions, 611726;NEURONAL CEROID LIPOFUSCINOSIS False 3 100;0;0 30.556 False ENSG00000243335 ENSG00000243335 HGNC:21957 KDM1A gene KDM1A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Cleft palate, psychomotor retardation, and distinctive facial features, 616728;Developmental delay 26077434;24838796;26656649 False 3 25;0;75 30.556 False ENSG00000004487 ENSG00000004487 HGNC:29079 KDM2B gene KDM2B Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with congenital cardiac defects and variable renal and ocular abnormalities, OMIM:621474 36322151;35128353;35710456 False 3 100;0;0 30.556 False ENSG00000089094 ENSG00000089094 HGNC:13610 KDM3B gene KDM3B Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Diets-Jongmans syndrome, OMIM:618846;Diets-Jongmans syndrome, MONDO:0030012 30929739 False 3 50;50;0 30.556 False ENSG00000120733 ENSG00000120733 HGNC:1337 KDM4B gene KDM4B Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Global developmental delay, intellectual disability and neuroanatomical defects 33232677 False 3 100;0;0 30.556 False ENSG00000127663 ENSG00000127663 HGNC:29136 KDM5A gene KDM5A Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal autism spectrum disorder, MONDO:0005258;intellectual disability, MONDO:0001071;El Hayek-Chahrour neurodevelopmental syndrome, OMIM:620820 21937992;33350388 False 3 33;17;50 30.556 False ENSG00000073614 ENSG00000073614 HGNC:9886 KDM5B gene KDM5B NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder, autosomal recessive 65, OMIM:618109 25363768;24307393;29276005;30409806;25529582;30217758 False 3 100;0;0 30.556 False ENSG00000117139 ENSG00000117139 HGNC:18039 KDM5C gene KDM5C NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Mental retardation, X-linked, syndromic, Claes-Jensen type, OMIM:300534 10982473;15586325;16538222;16541399;18203167;18697827;19826449;21575681;26919706;32279304 False 3 100;0;0 30.556 False ENSG00000126012 ENSG00000126012 HGNC:11114 KDM6A gene KDM6A Victorian Clinical Genetics Services;Expert Review Green;Eligibility statement prior genetic testing;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Kabuki syndrome 2, OMIM:300867 False 3 100;0;0 30.556 False ENSG00000147050 ENSG00000147050 HGNC:12637 KDM6B gene KDM6B NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, OMIM:618505;neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, MONDO:0032790 21937992;31124279;37196654 False 3 40;0;60 30.556 False ENSG00000132510 ENSG00000132510 HGNC:29012 KIAA0391 gene KIAA0391 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 54, OMIM:619737 34715011 False 3 100;0;0 30.556 False ENSG00000100890 ENSG00000100890 HGNC:19958 KIAA0391 gene KIAA0391 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 54, OMIM:619737 34715011 False 3 100;0;0 30.556 False ENSG00000100890 ENSG00000100890 HGNC:19958 KIAA0556 gene KIAA0556 Expert Review Green;NHS GMS;Literature;ClinGen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Joubert syndrome 26, OMIM:616784;Joubert syndrome 26, MONDO:0014771 26714646;27245168;31197031;31197031;36580738;40725402;40428346;32164589;30982090 False 3 100;0;0 30.556 False ENSG00000047578 ENSG00000047578 HGNC:29068 KIAA0586 gene KIAA0586 Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Joubert syndrome 23 616490 26096313 False 3 100;0;0 30.556 False ENSG00000100578 ENSG00000100578 HGNC:19960 KIAA1109 gene KIAA1109 Victorian Clinical Genetics Services;Literature;Expert Review Green;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Brain atrophy, Dandy Walker and Contractures;Alkuraya-Kucinskas syndrome,617822 25558065;29290337 False 3 100;0;0 30.556 False ENSG00000138688 ENSG00000138688 HGNC:26953 KIAA1161 gene KIAA1161 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Basal ganglia calcification, idiopathic, 7, autosomal recessive, OMIM:618317 30656188;30649222;30460687;29910000;31951047;33958240;31440850 False 3 100;0;0 30.556 False ENSG00000164976 ENSG00000164976 HGNC:19918 KIDINS220 gene KIDINS220 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Spastic paraplegia, intellectual disability, nystagmus, and obesity OMIM:617296 27005418;29667355;33763417 False 3 100;0;0 30.556 False ENSG00000134313 ENSG00000134313 HGNC:29508 KIF11 gene KIF11 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation, 152950;AUTOSOMAL-DOMINANT MICROCEPHALY ASSOCIATED WITH LYMPHEDEMA AND/OR CHORIORETINOPATHY False 3 100;0;0 30.556 False ENSG00000138160 ENSG00000138160 HGNC:6388 KIF14 gene KIF14 Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly 20, primary, autosomal recessive, OMIM:617914;Microcephaly 20, primary, autosomal recessive, MONDO:0054761 29343805;28892560 False 3 100;0;0 30.556 False ENSG00000118193 ENSG00000118193 HGNC:19181 KIF1A gene KIF1A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted NESCAV syndrome, OMIM:614255;Spastic paraplegia 30, autosomal dominant, OMIM:610357 False 3 100;0;0 30.556 False ENSG00000130294 ENSG00000130294 HGNC:888 KIF1BP gene KIF1BP Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Goldberg-Shprintzen megacolon syndrome, 609460 28277559 False 3 50;50;0 30.556 False ENSG00000198954 ENSG00000198954 HGNC:23419 KIF21B gene KIF21B Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Global developmental delay;Intellectual disability;Abnormality of brain morphology;Microcephaly 32415109 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000116852 ENSG00000116852 HGNC:29442 KIF2A gene KIF2A Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Cortical dysplasia, complex, with other brain malformations 3, 615411 23603762;21594994;27747449;27896282 False 3 25;75;0 30.556 False ENSG00000068796 ENSG00000068796 HGNC:6318 KIF4A gene KIF4A Expert Review Green;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females ?Intellectual developmental disorder, X-linked 100, OMIM:300923 24812067;34346154 False 3 50;0;50 30.556 False ENSG00000090889 ENSG00000090889 HGNC:13339 KIF5A gene KIF5A Victorian Clinical Genetics Services;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Myoclonus, intractable, neonatal, 617235;intellectual disability 22258533;27463701;27414745 False 3 75;0;25 30.556 False ENSG00000155980 ENSG00000155980 HGNC:6323 KIF5A gene KIF5A Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Myoclonus, intractable, neonatal, OMIM:617235 27463701;27414745 False 3 100;0;0 30.556 False ENSG00000155980 ENSG00000155980 HGNC:6323 KIF5C gene KIF5C Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 2; CDCBM2 23603762 False 3 100;0;0 30.556 False ENSG00000168280 ENSG00000168280 HGNC:6325 KIF7 gene KIF7 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hydrolethalus syndrome 2, 614120Acrocallosal syndrome, 200990Joubert syndrome 12, 200990;ACROCALLOSAL SYNDROME False 3 100;0;0 30.556 False ENSG00000166813 ENSG00000166813 HGNC:30497 KLF7 gene KLF7 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual disability 29251763 False 3 100;0;0 30.556 False ENSG00000118263 ENSG00000118263 HGNC:6350 KLHL20 gene KLHL20 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, OMIM:621390 36214804 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000076321 ENSG00000076321 HGNC:25056 KLHL7 gene KLHL7 Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal BOS-like phenotype 29074562;30300710;30142437 False 3 100;0;0 30.556 False ENSG00000122550 ENSG00000122550 HGNC:15646 KMT2A gene KMT2A Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Wiedemann-Steiner syndrome, OMIM:605130 False 3 100;0;0 30.556 False ENSG00000118058 ENSG00000118058 HGNC:7132 KMT2B gene KMT2B NHS GMS;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Dystonia 28, childhood-onset, OMIM:617284;Intellectual developmental disorder, autosomal dominant 68, OMIM:619934 25529582;27839873;27992417;29276005;25405613;29289525;29697234;31216378;33150406 False 3 100;0;0 30.556 False ENSG00000272333 ENSG00000272333 HGNC:15840 KMT2C gene KMT2C Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Kleefstra syndrome 2, 617768 22726846;29069077;29276005 False 3 0;0;100 30.556 False ENSG00000055609 ENSG00000055609 HGNC:13726 KMT2D gene KMT2D Victorian Clinical Genetics Services;Expert Review Green;Eligibility statement prior genetic testing Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Kabuki syndrome 1, OMIM:147920 False 3 100;0;0 30.556 False ENSG00000167548 ENSG00000167548 HGNC:7133 KMT2E gene KMT2E Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown O'Donnell-Luria-Rodan syndrome, 618512;Global developmental delay;Intellectual disability;Autism;Seizures;Abnormality of skull size 31079897;34321323 False 3 100;0;0 30.556 False ENSG00000005483 ENSG00000005483 HGNC:18541 KMT5B gene KMT5B Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Mental retardation, autosomal dominant 51, 617788 29276005;28191889;25363768 False 3 100;0;0 30.556 False ENSG00000110066 ENSG00000110066 HGNC:24283 KNL1 gene KNL1 Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly 4, primary, autosomal recessive, OMIM:604321;Microcephaly 4, primary, autosomal recessive, MONDO:0011437 22983954; 26621532; 26626498 False 3 100;0;0 30.556 False ENSG00000137812 ENSG00000137812 HGNC:24054 KPTN gene KPTN Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder, autosomal recessive 41, OMIM:615637;macrocephaly-developmental delay syndrome, MONDO:0014289 24239382 False 3 100;0;0 30.556 False ENSG00000118162 ENSG00000118162 HGNC:6404 KRAS gene KRAS Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Lung cancer, somatic, 211980Bladder cancer, somatic, 109800Pancreatic carcinoma, somatic, 260350Gastric cancer, somatic, 137215Leukemia, acute myelogenousNoonan syndrome 3, 609942Cardiofaciocutaneous syndrome 2, 615278Breast cancer, somatic, 114480SFM syndrome, somatic mosaic, 163200;CARDIOFACIOCUTANEOUS SYNDROME (CFC SYNDROME) False 3 100;0;0 30.556 False ENSG00000133703 ENSG00000133703 HGNC:6407 KYNU gene KYNU London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hydroxykynureninuria (Disorders of histidine, tryptophan or lysine metabolism);VACTERL-like phenotype;multiple congenital malformations;?Hydroxykynureninuria, 236800 27604308;17334708;28792876 False 3 0;0;100 30.556 False ENSG00000115919 ENSG00000115919 HGNC:6469 L1CAM gene L1CAM Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Corpus callosum, partial agenesis of, OMIM:304100;CRASH syndrome, OMIM:303350;MASA syndrome, OMIM:303350;Hydrocephalus due to aqueductal stenosis, OMIM:307000;Hydrocephalus with congential idiopathic intestinal pseudoobstruction, OMIM:307000;Hydrocephalus with Hirschsprung disease, OMIM:307000 False 3 100;0;0 30.556 False ENSG00000198910 ENSG00000198910 HGNC:6470 L2HGDH gene L2HGDH Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal L-2-hydroxyglutaric aciduria, 236792 25655951 False 3 0;0;0 30.556 False ENSG00000087299 ENSG00000087299 HGNC:20499 L2HGDH gene L2HGDH NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal L-2-hydroxyglutaric aciduria, 236792 27604308 False 3 0;0;100 30.556 False ENSG00000087299 ENSG00000087299 HGNC:20499 L2HGDH gene L2HGDH Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal L-2-hydroxyglutaric aciduria, 236792;L-2-HYDROXYGLUTARIC ACIDURIA (L2HGA) False 3 100;0;0 30.556 False ENSG00000087299 ENSG00000087299 HGNC:20499 LAMA1 gene LAMA1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Poretti-Boltshauser syndrome OMIM:615960;ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome MONDO:0014419 21937992;30244536;25105227 False 3 100;0;0 30.556 False ENSG00000101680 ENSG00000101680 HGNC:6481 LAMA2 gene LAMA2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy, congenital merosin-deficient, 607855Muscular dystrophy, congenital, due to partial LAMA2 deficiency, 607855;CONGENITAL MUSCULAR DYSTROPHY False 3 100;0;0 30.556 False ENSG00000196569 ENSG00000196569 HGNC:6482 LAMB1 gene LAMB1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Lissencephaly 5, OMIM:615191 0 False 3 0;100;0 30.556 False ENSG00000091136 ENSG00000091136 HGNC:6486 LAMB1 gene LAMB1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Lissencephaly 5, OMIM:615191;Cystic leukoencephalopathy 23472759;25925986;29888467 False 3 50;50;0 30.556 False ENSG00000091136 ENSG00000091136 HGNC:6486 LAMP2 gene LAMP2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Danon disease 27604308 False 3 100;0;0 30.556 False ENSG00000005893 ENSG00000005893 HGNC:6501 LAMP2 gene LAMP2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Danon disease, 300257;DANON DISEASE (DAND) False 3 100;0;0 30.556 False ENSG00000005893 ENSG00000005893 HGNC:6501 LARGE1 gene LARGE1 Victorian Clinical Genetics Services;Gene2Phenotype;Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen;UKGTN Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, 613154;Muscle-eye-brain disease;MDDGA6;Walker-Warburg syndrome;Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6, 608840;congenital muscular dystrophy-dystroglycanopathy with mental retardation;MDDGB6;Intellectual disability 12966029;19067344;17436019;19299310;21248746 False 3 100;0;0 30.556 False ENSG00000133424 ENSG00000133424 HGNC:6511 LARGE1 gene LARGE1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal N-acetylglucosaminyltransferase-like protein deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies);Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6 608840;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6 613154;N-acetylglucosaminyltransferase-like protein deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) 27604308 False 3 0;0;0 30.556 False ENSG00000133424 ENSG00000133424 HGNC:6511 LARP7 gene LARP7 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Alazami syndrome, 615071;ALAZAMI SYNDROME False 3 100;0;0 30.556 False ENSG00000174720 ENSG00000174720 HGNC:24912 LARS gene LARS Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Infantile liver failure syndrome 1, 615438 28774368;30349989;22607940 False 3 100;0;0 30.556 False ENSG00000133706 ENSG00000133706 HGNC:6512 LARS gene LARS Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Infantile liver failure syndrome 1, MIM# 615438 32699352 False 3 100;0;0 30.556 False ENSG00000133706 ENSG00000133706 HGNC:6512 LARS2 gene LARS2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Perrault syndrome 4, OMIM:615300;Hydrops, lactic acidosis, and sideroblastic anemia, OMIM:617021;Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only);Multiple respiratory chain complex deficiencies (disorders of protein synthesis False 3 100;0;0 30.556 True ENSG00000011376 ENSG00000011376 HGNC:17095 LARS2 gene LARS2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Perrault syndrome 4, OMIM:615300;Hydrops, lactic acidosis, and sideroblastic anemia, OMIM:617021;Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only);Multiple respiratory chain complex deficiencies (disorders of protein synthesis 27604308 False 3 100;0;0 30.556 False ENSG00000011376 ENSG00000011376 HGNC:17095 LBR gene LBR Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal ?Reynolds syndrome 613471;Greenberg skeletal dysplasia 215140;Pelger-Huet anomaly 169400;Pelger-Huet anomaly with mild skeletal anomalies 618019 27604308;12118250;14617022;18382993;21327084;14684697;25348816;23824842 False 3 0;0;0 30.556 False ENSG00000143815 ENSG00000143815 HGNC:6518 LCAT gene LCAT London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Norum disease/LCAT deficiency, 245900;Fish-eye disease, 136120;Lecithin cholesterol acyltransferase deficiency (Disorders of high density lipoprotein metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000213398 ENSG00000213398 HGNC:6522 LCT gene LCT London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Lactose intolerance (Other carbohydrate disorders);Lactase deficiency, congenital, 223000 27604308 False 3 100;0;0 30.556 False ENSG00000115850 ENSG00000115850 HGNC:6530 LDHA gene LDHA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycogen Storage Disease;Glycogen storage disease XI, 612933;Muscle LDH deficiency (Glycogen storage disorders) 27604308 False 3 100;0;0 30.556 False ENSG00000134333 ENSG00000134333 HGNC:6535 LDLR gene LDLR Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Hypercholesterolemia, familial, 1 143890;LDL cholesterol level QTL2 143890 27604308;27821657;30311388 False 3 0;0;0 30.556 False ENSG00000130164 ENSG00000130164 HGNC:6547 LDLRAP1 gene LDLRAP1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypercholesterolemia, familial, 4 603813 27604308;11326085;12016260;12958143;15599766;29245109 False 3 0;0;0 30.556 False ENSG00000157978 ENSG00000157978 HGNC:18640 LETM1 gene LETM1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089 36055214 False 3 50;25;25 30.556 False ENSG00000168924 ENSG00000168924 HGNC:6556 LETM1 gene LETM1 NHS GMS;Expert Review Green;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089 36055214;33815143 False 3 100;0;0 30.556 False ENSG00000168924 ENSG00000168924 HGNC:6556 LETM1 gene LETM1 NHS GMS;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089 36055214;33815143 False 3 33;33;33 30.556 False ENSG00000168924 ENSG00000168924 HGNC:6556 LFNG gene LFNG Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spondylocostal dysostosis 3, autosomal recessive, OMIM:609813;O-fucose-specific beta-1,3-N-acetylglucosaminyltransferase deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) 16385447;29459493;30196550;30531807;33728697;34645488;37038048;38565611 False 3 67;0;33 30.556 False ENSG00000106003 ENSG00000106003 HGNC:6560 LGI3 gene LGI3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects, OMIM:620007 35948005 False 3 100;0;0 30.556 False ENSG00000168481 ENSG00000168481 HGNC:18711 LHX2 gene LHX2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown neurodevelopmental disorder, MONDO:0700092 37057675 False 3 100;0;0 30.556 False ENSG00000106689 ENSG00000106689 HGNC:6594 LIAS gene LIAS Expert Review Green;Literature;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperglycinemia, lactic acidosis, and seizures, 614462 22152680;26108146;24334290;30914295 False 3 50;50;0 30.556 False ENSG00000121897 ENSG00000121897 HGNC:16429 LIAS gene LIAS Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pyruvate dehydrogenase lipoic acid synthetase deficiency, 614462 False 3 100;0;0 30.556 True ENSG00000121897 ENSG00000121897 HGNC:16429 LIAS gene LIAS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pyruvate dehydrogenase lipoic acid synthetase deficiency, 614462;Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) 27604308 False 3 100;0;0 30.556 False ENSG00000121897 ENSG00000121897 HGNC:16429 LIG3 gene LIG3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 20 (MNGIE type), OMIM:619780 33855352 False 3 100;0;0 30.556 False ENSG00000005156 ENSG00000005156 HGNC:6600 LIG3 gene LIG3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 20 (MNGIE type), OMIM:619780 33855352 False 3 100;0;0 30.556 False ENSG00000005156 ENSG00000005156 HGNC:6600 LIG3 gene LIG3 Expert Review Green;Literature;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 20 (MNGIE type), OMIM:619780 33855352 False 3 100;0;0 30.556 True ENSG00000005156 ENSG00000005156 HGNC:6600 LIG4 gene LIG4 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal LIG4 syndrome, OMIM:606593 False 3 100;0;0 30.556 False ENSG00000174405 ENSG00000174405 HGNC:6601 LINC01578 gene LINC01578 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with dysmorphic facies, absent speech and ambulation, and brain abnormalities, OMIM:621012 39442041 False 3 100;0;0 30.556 False ENSG00000272888 ENSG00000272888 HGNC:48626 LINGO4 gene LINGO4 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;speech disorder 33098801 False 3 100;0;0 30.556 False ENSG00000213171 ENSG00000213171 HGNC:31814 LINS1 gene LINS1 Victorian Clinical Genetics Services;Other;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal AUTOSOMAL RECESSIVE MENTAL RETARDATION;Mental retardation, autosomal recessive 27, 614340 21937992;23773660;28181389;30090841 False 3 100;0;0 30.556 False ENSG00000140471 ENSG00000140471 HGNC:30922 LIPA gene LIPA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cholesteryl ester storage disease 27604308 False 3 0;0;0 30.556 False ENSG00000107798 ENSG00000107798 HGNC:6617 LIPT1 gene LIPT1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Lipoyltransferase 1 deficiency False 3 100;0;0 30.556 False ENSG00000144182 ENSG00000144182 HGNC:29569 LIPT1 gene LIPT1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Lipoyltransferase 1 deficiency False 3 100;0;0 30.556 True ENSG00000144182 ENSG00000144182 HGNC:29569 LIPT1 gene LIPT1 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Lipoyltransferase 1 deficiency, MIM#616299 24341803;24256811;29681092 False 3 100;0;0 30.556 False ENSG00000144182 ENSG00000144182 HGNC:29569 LIPT2 gene LIPT2 Expert Review Green;Expert Review;Other Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities, 617668 28757203;28803783 False 3 0;100;0 30.556 False ENSG00000175536 ENSG00000175536 HGNC:37216 LIPT2 gene LIPT2 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities, 617668 28803783;28757203 False 3 0;100;0 30.556 False ENSG00000175536 ENSG00000175536 HGNC:37216 LMBRD1 gene LMBRD1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Methylmalonic aciduria and homocystinuria, cblF type, 277380 27604308 False 3 0;0;0 30.556 False ENSG00000168216 ENSG00000168216 HGNC:23038 LMBRD2 gene LMBRD2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Developmental delay with variable neurologic and brain abnormalities, OMIM:619694 32820033;https://doi.org/10.1101/797787 False 3 0;100;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000164187 ENSG00000164187 HGNC:25287 LMF1 gene LMF1 NHS GMS;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Lipase deficiency, combined OMIM:246650;lipase deficiency, combined MONDO:0009527 17994020;19820022;30885219;30420299;29910226;22239554 False 3 100;0;0 30.556 False ENSG00000103227 ENSG00000103227 HGNC:14154 LMNB1 gene LMNB1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Microcephaly 26, primary, autosomal dominant, OMIM:619179 32910914;33033404 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000113368 ENSG00000113368 HGNC:6637 LMNB1 gene LMNB1 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Leukodystrophy, adult-onset, autosomal dominant, OMIM:169500 21225301;25655951;21909802 False 3 0;0;0 30.556 False Other - please provide details in the comments ENSG00000113368 ENSG00000113368 HGNC:6637 LONP1 gene LONP1 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal CODAS syndrome, 600373;Cerebral, ocular, dental, auricular, and skeletal anomalies syndrome 25574826;20503327;11471171;1887855 False 3 0;100;0 30.556 False ENSG00000196365 ENSG00000196365 HGNC:9479 LONP1 gene LONP1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal CODAS (cerebral, ocular, dental, auricular and skeletal) syndrome (MIM 600373) 25574826;25808063 False 3 100;0;0 30.556 False ENSG00000196365 ENSG00000196365 HGNC:9479 LONP1 gene LONP1 Victorian Clinical Genetics Services;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal CODAS (cerebral, ocular, dental, auricular and skeletal) syndrome (MIM 600373) PMID: 25574826; PMID: 25808063 False 3 100;0;0 30.556 True ENSG00000196365 ENSG00000196365 HGNC:9479 LPIN1 gene LPIN1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Myoglobinuria, acute recurrent, autosomal recessive 27604308 False 3 100;0;0 30.556 False ENSG00000134324 ENSG00000134324 HGNC:13345 LPL gene LPL London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Lipoprotein lipase deficiency, 238600;Combined hyperlipidemia, familial, 144250;Familial lipoprotein lipase deficiency (Familial chylomicronaemia, Inherited hypercholesterolaemias) 27604308 False 3 100;0;0 30.556 False ENSG00000175445 ENSG00000175445 HGNC:6677 LRP2 gene LRP2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Donnai-Barrow syndrome, 222448;INTELLECTUAL DISABILITY False 3 100;0;0 30.556 False ENSG00000081479 ENSG00000081479 HGNC:6694 LRPPRC gene LRPPRC London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leigh syndrome, French-Canadian type, 220111;Mitochondrial Diseases;Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Isolated complex IV deficiency;Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors) 27604308 False 3 100;0;0 30.556 False ENSG00000138095 ENSG00000138095 HGNC:15714 LRPPRC gene LRPPRC Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leigh syndrome, French-Canadian type, 220111;LEIGH SYNDROME, FRENCH-CANADIAN TYPE False 3 100;0;0 30.556 False ENSG00000138095 ENSG00000138095 HGNC:15714 LRPPRC gene LRPPRC Victorian Clinical Genetics Services;Expert Review Green;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex IV deficiency;Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Leigh syndrome, French-Canadian type, 220111;Mitochondrial Diseases False 3 100;0;0 30.556 True ENSG00000138095 ENSG00000138095 HGNC:15714 LRRC7 gene LRRC7 Expert Review Green;NHS GMS;Literature;Expert Review Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual developmental disorder, autosomal dominant 77, OMIM:621415;intellectual developmental disorder, autosomal dominant 77, MONDO:0980748 36928819;39256359 False 3 100;0;0 30.556 False ENSG00000033122 ENSG00000033122 HGNC:18531 LSS gene LSS Expert Review Green;Expert Review;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Alopecia;Abnormality of the skin;Cataract 44, Hypotrichosis 14, 616509, 618275;Microcephaly;Seizures;Abnormality of the genital system;Hypotonia;Intellectual disability;Global developmental delay 30723320;26200341;30401459;29016354 False 3 100;0;0 30.556 False ENSG00000160285 ENSG00000160285 HGNC:6708 LYRM4 gene LYRM4 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 19, OMIM:615595 23814038;31497476 False 3 100;0;0 30.556 False ENSG00000214113 ENSG00000214113 HGNC:21365 LYRM4 gene LYRM4 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 19, OMIM:615595 23814038;31497476 False 3 75;25;0 30.556 False ENSG00000214113 ENSG00000214113 HGNC:21365 LYRM7 gene LYRM7 Expert Review Green;Victorian Clinical Genetics Services;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex III deficiency;Mitochondrial complex III deficiency, nuclear type 8;615838;leukoencephalopathy and complex III deficiency;severe encephalopathy, lactic acidosis and profound, isolated cIII deficiency in skeletal muscle 27564080;27151179;27151179;27151179;26912632;24014394;28694194 False 3 100;0;0 30.556 False ENSG00000186687 ENSG00000186687 HGNC:28072 LYRM7 gene LYRM7 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex III deficiency, nuclear type 8, MIM#615838 False 3 100;0;0 30.556 False ENSG00000186687 ENSG00000186687 HGNC:28072 LYRM7 gene LYRM7 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex III deficiency, nuclear type 8;leukoencephalopathy and complex III deficiency;615838;severe encephalopathy, lactic acidosis and profound, isolated cIII deficiency in skeletal muscle 27151179;27564080 False 3 0;0;0 30.556 False ENSG00000186687 ENSG00000186687 HGNC:28072 LYRM7 gene LYRM7 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex III deficiency, nuclear type 8;Isolated complex III deficiency;severe encephalopathy, lactic acidosis and profound, isolated cIII deficiency in skeletal muscle;leukoencephalopathy and complex III deficiency;615838 27564080;24014394;28694194;27151179;26912632 False 3 100;0;0 30.556 False ENSG00000186687 ENSG00000186687 HGNC:28072 LZTR1 gene LZTR1 Expert Review Green;Other Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Noonan syndrome 10;Prenatal hydrops;increased nuchal translucency;cardiac findings 25795793;29469822 False 3 0;0;0 30.556 False ENSG00000099949 ENSG00000099949 HGNC:6742 MAB21L1 gene MAB21L1 Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Global developmental delay;Intellectual disability;Cerebellar hypoplasia;Abnormality of the eye;Abnormality of the genital system;No OMIM number 27103078;30487245 False 3 100;0;0 30.556 False ENSG00000180660 ENSG00000180660 HGNC:6757 MAB21L2 gene MAB21L2 Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal MICROPHTHALMIA, SYNDROMIC 14; MCOPS14 24906020 False 3 33;67;0 30.556 False ENSG00000181541 ENSG00000181541 HGNC:6758 MACF1 gene MACF1 Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual disability;Seizures;Lissencephaly;Brainstem dysplasia;Lissencephaly 9 with complex brainstem malformation, 618325 30471716;16815997 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000127603 ENSG00000127603 HGNC:13664 MADD gene MADD Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal DEEAH syndrome, OMIM:619004;deeah syndrome, MONDO:0033561: Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia, OMIM:619005;neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia, MONDO:0033562 28940097;29302074;32761064 False 3 100;0;0 30.556 False ENSG00000110514 ENSG00000110514 HGNC:6766 MAF gene MAF Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted CATARACT, DEAFNESS, INTELLECTUAL DISABILITY, SEIZURES, AND A DOWN SYNDROME-LIKE FACIES 0 False 3 100;0;0 30.556 False ENSG00000178573 ENSG00000178573 HGNC:6776 MAG gene MAG Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 75, autosomal recessive, OMIM:616680;hereditary spastic paraplegia 75, MONDO:0014729 24482476;26179919;27606346;31402626;39336794 False 3 100;0;0 30.556 False ENSG00000105695 ENSG00000105695 HGNC:6783 MAGEL2 gene MAGEL2 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) PRADER WILLI SYNDROME 24076603;25529582;29599419;29588991 False 3 25;50;25 30.556 False ENSG00000254585 ENSG00000254585 HGNC:6814 MAGT1 gene MAGT1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia 300853 27604308;27393411;29581357;25956530;21796205 False 3 0;0;0 30.556 False ENSG00000102158 ENSG00000102158 HGNC:28880 MAN1B1 gene MAN1B1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mental Retardation, Recessive;Mental retardation, autosomal recessive 15, 614202;AUTOSOMAL RECESSIVE MENTAL RETARDATION 21763484;21937992 False 3 100;0;0 30.556 False ENSG00000177239 ENSG00000177239 HGNC:6823 MAN1B1 gene MAN1B1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MAN1B1-CDG (Disorders of protein N-glycosylation);Mental retardation, autosomal recessive 15 614202 27604308 False 3 0;0;0 30.556 False ENSG00000177239 ENSG00000177239 HGNC:6823 MAN2B1 gene MAN2B1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mannosidosis, alpha-, types I and II, 248500;LYSOSOMAL ALPHA-MANNOSIDOSIS (AM) False 3 100;0;0 30.556 False ENSG00000104774 ENSG00000104774 HGNC:6826 MAN2B1 gene MAN2B1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mannosidosis, alpha-, types I and II 27604308 False 3 0;0;0 30.556 False ENSG00000104774 ENSG00000104774 HGNC:6826 MAN2B2 gene MAN2B2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation type 1EE with or without immunodeficiency, OMIM:621140 31775018;35637269;38622837 False 3 100;0;0 30.556 False ENSG00000013288 ENSG00000013288 HGNC:29623 MAN2C1 gene MAN2C1 Expert Review Green;NHS GMS;Other;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of deglycosylation 2, OMIM:619775 35045343 False 3 100;0;0 30.556 False ENSG00000140400 ENSG00000140400 HGNC:6827 MANBA gene MANBA Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal "Mannosidosis, beta 248510" 27604308 False 3 0;0;0 30.556 False ENSG00000109323 ENSG00000109323 HGNC:6831 MANBA gene MANBA Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mannosidosis, beta, 248510;LYSOSOMAL BETA-MANNOSIDOSIS (LYSBMAN) False 3 100;0;0 30.556 False ENSG00000109323 ENSG00000109323 HGNC:6831 MAOA gene MAOA Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Brunner syndrome, 300615;BRUNNER SYNDROME (BRUNS) False 3 100;0;0 30.556 False ENSG00000189221 ENSG00000189221 HGNC:6833 MAOA gene MAOA Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Brunner syndrome 300615;{Antisocial behavior} 300615 27604308;8211186;24169519;25807999 False 3 0;0;0 30.556 False ENSG00000189221 ENSG00000189221 HGNC:6833 MAP1B gene MAP1B Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Periventricular nodular heterotopia 9, 618918 30150678;29738522;30214071;31317654 False 3 67;33;0 30.556 False ENSG00000131711 ENSG00000131711 HGNC:6836 MAP2K1 gene MAP2K1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Cardiofaciocutaneous syndrome 3, 615279;CARDIOFACIOCUTANEOUS SYNDROME (CFC SYNDROME) False 3 100;0;0 30.556 False ENSG00000169032 ENSG00000169032 HGNC:6840 MAP2K2 gene MAP2K2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Cardiofaciocutaneous syndrome 4, 615280;CARDIOFACIOCUTANEOUS SYNDROME (CFC SYNDROME) False 3 100;0;0 30.556 False ENSG00000126934 ENSG00000126934 HGNC:6842 MAP4K4 gene MAP4K4 Expert Review Green;NHS GMS;DD-Gene2Phenotype;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown MAP4K4-related neurodevelopmental disorder with/without congenital anomalies;multiple congenital anomalies;neurodevelopmental differences 36469137;28518170;37126546;37126546 False 3 100;0;0 30.556 False Other ENSG00000071054 ENSG00000071054 HGNC:6866 MAPK1 gene MAPK1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Noonan syndrome 13, OMIM:619087 32721402 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000100030 ENSG00000100030 HGNC:6871 MAPK8IP3 gene MAPK8IP3 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with or without variable brain abnormalities, OMIM:618443 30612693;25363768;28213671;28135719 False 3 100;0;0 30.556 False ENSG00000138834 ENSG00000138834 HGNC:6884 MAPKAPK5 gene MAPKAPK5 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurocardiofaciodigital syndrome, OMIM:619869 33442026;35575217;36581449 False 3 100;0;0 30.556 False ENSG00000089022 ENSG00000089022 HGNC:6889 MAPRE2 gene MAPRE2 NHS GMS;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Symmetric circumferential skin creases, congenital, 2, 616734 26637975;31903734;31502381 False 3 100;0;0 30.556 False Other - please provide details in the comments ENSG00000166974 ENSG00000166974 HGNC:6891 MARK2 gene MARK2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual developmental disorder, autosomal dominant 76, OMIM:621285;intellectual developmental disorder, autosomal dominant 76, MONDO:0979575 39419027;39436150 False 3 100;0;0 30.556 False ENSG00000072518 ENSG00000072518 HGNC:3332 MARS2 gene MARS2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Spastic Ataxia 13, autosomal recessive, 611390;?Combined oxidative phosphorylation deficiency 25 22448145;25754315 False 3 50;50;0 30.556 True ENSG00000247626 ENSG00000247626 HGNC:25133 MARS2 gene MARS2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic Ataxia 13, autosomal recessive, 611390;Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only));?Combined oxidative phosphorylation deficiency 25 27604308 False 3 100;0;0 30.556 False ENSG00000247626 ENSG00000247626 HGNC:25133 MASP1 gene MASP1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3MC SYNDROME 1; 3MC1 21258343;21035106;17937425 False 3 33;67;0 30.556 False ENSG00000127241 ENSG00000127241 HGNC:6901 MAST1 gene MAST1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Global developmental delay, Intellectual disability, Abnormality of the corpus callosum, Cerebellar hypoplasia, Abnormality of the cerebral cortex, Seizures;Global developmental delay, Intellectual disability, Microcephaly, Autism, Seizures;Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations, 618273 30449657;28135719;25666757;27479843 False 3 100;0;0 30.556 False ENSG00000105613 ENSG00000105613 HGNC:19034 MAST3 gene MAST3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown 34185323;35095415 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000099308 ENSG00000099308 HGNC:19036 MAST4 gene MAST4 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder MONDO:0700092, MAST4-related 36910266;33057194 False 3 100;0;0 30.556 False ENSG00000069020 ENSG00000069020 HGNC:19037 MAT1A gene MAT1A London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Hypermethioninemia, persistent, autosomal dominant, due to methionine adenosyltransferase I/III deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000151224 ENSG00000151224 HGNC:6903 MAT1A gene MAT1A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Hypermethioninemia, persistent, autosomal dominant, due to methionine adenosyltransferase I/IIIdeficiency, 250850Methionine adenosyltransferase deficiency, autosomal recessive, 250850;METHIONINE ADENOSYLTRANSFERASE DEFICIENCY False 3 100;0;0 30.556 False ENSG00000151224 ENSG00000151224 HGNC:6903 MBD5 gene MBD5 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Mental Retardation, Dominant;Autosomal Dominant Mental Retardation syndrome type 1;Mental retardation, autosomal dominant 1, 156200;EHMT1-LIKE INTELLECTUAL DISABILITY False 3 100;0;0 30.556 False ENSG00000204406 ENSG00000204406 HGNC:20444 MBOAT7 gene MBOAT7 Victorian Clinical Genetics Services;Gene2Phenotype;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mental retardation, autosomal recessive 57, 617188;Intellectual Disability Accompanied by Epilepsy and Autistic Features;Autosomal recessive non-syndromic intellectual disability 27616480;23097495 False 3 0;0;0 30.556 False ENSG00000125505 ENSG00000125505 HGNC:15505 MBTPS2 gene MBTPS2 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) IFAP syndrome with or without BRESHECK syndrome 308205;IFAP syndrome with or without BRESHECK syndrome,308205;Ichthyosis follicularis, atrichia, and photophobia with or without brain anomalies, retardation, ectodermal dysplasia, skeletal malformations, hirschsprung disease, ear/eye anomalies, cleft palate/cryptorchidism, and kidney dysplasia/hypoplasia 21426410;22105905;24090718;23316014;21179107;19361614 False 3 0;0;100 30.556 False ENSG00000012174 ENSG00000012174 HGNC:15455 MCCC1 gene MCCC1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-Methylcrotonyl-CoA carboxylase 1 deficiency, 210200;3-METHYLCROTONYL-COA CARBOXYLASE DEFICIENCY False 3 100;0;0 30.556 False ENSG00000078070 ENSG00000078070 HGNC:6936 MCCC1 gene MCCC1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-Methylcrotonyl-CoA carboxylase 1 deficiency, 210200 27604308;24816252 False 3 0;0;0 30.556 False ENSG00000078070 ENSG00000078070 HGNC:6936 MCCC2 gene MCCC2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-Methylcrotonyl-CoA carboxylase 2 deficiency, 210210 27604308 False 3 0;0;0 30.556 False ENSG00000131844 ENSG00000131844 HGNC:6937 MCCC2 gene MCCC2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-Methylcrotonyl-CoA carboxylase 2 deficiency, 210210;3-METHYLCROTONYL-COA CARBOXYLASE 2 DEFICIENCY False 3 100;0;0 30.556 False ENSG00000131844 ENSG00000131844 HGNC:6937 MCEE gene MCEE London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Methylmalonyl-CoA epimerase deficiency (Organic acidurias);Methylmalonyl-CoA epimerase deficiency;metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections 27604308 False 3 0;0;0 30.556 False ENSG00000124370 ENSG00000124370 HGNC:16732 MCM3AP gene MCM3AP Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development, 618124 24123876;28633435;28969388;29982295;32202298 False 3 50;50;0 30.556 False ENSG00000160294 ENSG00000160294 HGNC:6946 MCOLN1 gene MCOLN1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mucolipidosis, Type IV;Mucolipidosis IV (Other lysosomal disorders) 27604308 False 3 0;0;0 30.556 False ENSG00000090674 ENSG00000090674 HGNC:13356 MCOLN1 gene MCOLN1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mucolipidosis IV False 3 0;0;0 30.556 False ENSG00000090674 ENSG00000090674 HGNC:13356 MCOLN1 gene MCOLN1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mucolipidosis IV, 252650;MUCOLIPIDOSIS IV False 3 100;0;0 30.556 False ENSG00000090674 ENSG00000090674 HGNC:13356 MCPH1 gene MCPH1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly 1, primary, autosomal recessive, OMIM:251200 30500859;16311745;20978018;7693575;11857108;12046007 False 3 100;0;0 30.556 False ENSG00000147316 ENSG00000147316 HGNC:6954 MDH2 gene MDH2 Expert Review Green;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epileptic encephalopathy, early infantile, 51 617339 27989324 False 3 100;0;0 30.556 False ENSG00000146701 ENSG00000146701 HGNC:6971 MDH2 gene MDH2 Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epileptic encephalopathy, early infantile, 51, 617339 27989324 False 3 100;0;0 30.556 False ENSG00000146701 ENSG00000146701 HGNC:6971 MDH2 gene MDH2 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal "Epileptic encephalopathy, early infantile, 51 617339" 27989324 False 3 100;0;0 30.556 False ENSG00000146701 ENSG00000146701 HGNC:6971 MECP2 gene MECP2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Encephalopathy, neonatal severe, OMIM:300673;Intellectual developmental disorder, X-linked syndromic 13, OMIM:300055;Intellectual developmental disorder, X-linked syndromic, Lubs type, OMIM:300260;Rett syndrome, OMIM:312750;Rett syndrome, atypical, OMIM:312750;Rett syndrome, preserved speech variant, OMIM:312750 False 3 100;0;0 30.556 False ENSG00000169057 ENSG00000169057 HGNC:6990 MECR gene MECR Expert Review Green;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities 617282 27817865 False 3 100;0;0 30.556 False ENSG00000116353 ENSG00000116353 HGNC:19691 MECR gene MECR Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities 617282 27817865 False 3 100;0;0 30.556 False ENSG00000116353 ENSG00000116353 HGNC:19691 MED11 gene MED11 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, OMIM:620327 36001086 False 3 100;0;0 30.556 False ENSG00000161920 ENSG00000161920 HGNC:32687 MED12 gene MED12 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Opitz-Kaveggia syndrome, 305450;Lujan-Fryns syndrome, 309520;Ohdo syndrome, X-linked, 300895;OPITZ-KAVEGGIA SYNDROME (OKS) 33244165;34079076;33244166;25529582;24896178 False 3 100;0;0 30.556 False ENSG00000184634 ENSG00000184634 HGNC:11957 MED12L gene MED12L Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Nizon-Isidor syndrome, OMIM:618872;Nizon-Isidor syndrome, MONDO:0030030 31155615;36212160;35920825;40957966 False 3 67;33;0 30.556 False ENSG00000144893 ENSG00000144893 HGNC:16050 MED13 gene MED13 Expert Review Green;NHS GMS;Literature;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Delayed speech and language development;Motor delay;Intellectual disability;Autistic behavior;Attention deficit hyperactivity disorder;Abnormality of the eye;Constipation 29740699 False 3 67;33;0 30.556 False ENSG00000108510 ENSG00000108510 HGNC:22474 MED13L gene MED13L Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Impaired intellectual development and distinctive facial features with or without cardiac defects, OMIM:616789 14638541;23403903;24781760;25167861;25712080;25758992 False 3 100;0;0 30.556 False ENSG00000123066 ENSG00000123066 HGNC:22962 MED16 gene MED16 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Guillouet-Gordon syndrome, OMIM:621220 40081376 False 3 100;0;0 30.556 False ENSG00000175221 ENSG00000175221 HGNC:17556 MED17 gene MED17 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly, postnatal progressive, with seizures and brain atrophy, 613668;MICROCEPHALY, POSTNATAL PROGRESSIVE, WITH SEIZURES AND BRAIN ATROPHY False 3 100;0;0 30.556 False ENSG00000042429 ENSG00000042429 HGNC:2375 MED23 gene MED23 Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mental retardation, autosomal recessive 18, 614249;MRT18;Intellectual disability 21868677;25845469;25527630;22129135;27311965;21868677;25845469 False 3 33;0;67 30.556 False ENSG00000112282 ENSG00000112282 HGNC:2372 MED25 gene MED25 Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Basel-Vanagait-Smirin-Yosef syndrome, 616449;BVSYS;Syndromic intellectual disability;Congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome 25792360;25527630;30800049;DOI:10.1159/000501114 False 3 50;50;0 30.556 False ENSG00000104973 ENSG00000104973 HGNC:28845 MED27 gene MED27 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;Axial hypotonia;Spasticity;Dystonia;Cerebellar hypoplasia;Cataracts;Epilepsy 33443317 False 3 100;0;0 30.556 False ENSG00000160563 ENSG00000160563 HGNC:2377 MEF2C gene MEF2C Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Mental Retardation, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations False 3 0;0;0 30.556 False ENSG00000081189 ENSG00000081189 HGNC:6996 MEF2C gene MEF2C Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, 613443;MRSME;Chromosome 5q14.3 deletion syndrome, 613443 20513142;19592390;23001426;25529582;24896178 False 3 100;0;0 30.556 False ENSG00000081189 ENSG00000081189 HGNC:6996 MEIS2 gene MEIS2 Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Cleft palate, cardiac defects, and mental retardation, OMIM:600987;Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies, MONDO:0010970 27225850;24678003;25712757;30291340;30055086 False 3 100;0;0 30.556 False ENSG00000134138 ENSG00000134138 HGNC:7001 METTL23 gene METTL23 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mental retardation, autosomal recessive 44, 615942 24501276;24626631 False 3 100;0;0 30.556 False ENSG00000181038 ENSG00000181038 HGNC:26988 METTL5 gene METTL5 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder, autosomal recessive 72, OMIM:618665 29302074;31564433;https://imgc2019.sciencesconf.org/data/abstract_book_complete.pdf False 3 100;0;0 30.556 False ENSG00000138382 ENSG00000138382 HGNC:25006 MFF gene MFF Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal "Encephalopathy due to defective mitochondrial and peroxisomal fission 2 617086" False 3 100;0;0 30.556 False ENSG00000168958 ENSG00000168958 HGNC:24858 MFF gene MFF Expert Review Green;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Encephalopathy due to defective mitochondrial and peroxisomal fission 2 617086 False 3 100;0;0 30.556 False ENSG00000168958 ENSG00000168958 HGNC:24858 MFF gene MFF London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Encephalopathy due to defective mitochondrial and peroxisomal fission 2;Encephalopathy due to defective mitochondrial and peroxisomal fission 2, 617086;Disorders of mitochondrial dynamics, fusion and fission (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) 27604308 False 3 100;0;0 30.556 False ENSG00000168958 ENSG00000168958 HGNC:24858 MFN2 gene MFN2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Charcot-Marie-Tooth disease, axonal, type 2A2A, OMIM:609260;Charcot-Marie-Tooth disease, axonal, type 2A2B, OMIM:617087;Hereditary motor and sensory neuropathy VIA, OMIM:601152 27604308 False 3 100;0;0 30.556 False ENSG00000116688 ENSG00000116688 HGNC:16877 MFN2 gene MFN2 Victorian Clinical Genetics Services;Expert Review Green;UKGTN;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Charcot-Marie-Tooth disease, axonal, type 2A2A, OMIM:609260;Charcot-Marie-Tooth disease, axonal, type 2A2B, OMIM:617087;Hereditary motor and sensory neuropathy VIA, OMIM:601152 False 3 100;0;0 30.556 True ENSG00000116688 ENSG00000116688 HGNC:16877 MFSD2A gene MFSD2A NHS GMS;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities, 616486 26005868;26005865;29302074;30043326;32572202 False 3 100;0;0 30.556 False ENSG00000168389 ENSG00000168389 HGNC:25897 MFSD8 gene MFSD8 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MFSD8-RELATED NEURONAL CEROID-LIPOFUSCINOSIS 0 False 3 33;67;0 30.556 False ENSG00000164073 ENSG00000164073 HGNC:28486 MFSD8 gene MFSD8 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ceroid lipofuscinosis, neuronal, 7 61095 False 3 0;0;0 30.556 False ENSG00000164073 ENSG00000164073 HGNC:28486 MGAT2 gene MGAT2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal N-acetylglucosaminyltransferase deficiency (Disorders of protein N-glycosylation);Congenital disorder of glycosylation, type IIa 212066 19419693 False 3 0;0;0 30.556 False ENSG00000168282 ENSG00000168282 HGNC:7045 MGAT2 gene MGAT2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIa, 212066;CONGENITAL DISORDER OF GLYCOSYLATION TYPE 2A (CDG2A) False 3 100;0;0 30.556 False ENSG00000168282 ENSG00000168282 HGNC:7045 MGME1 gene MGME1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Mitochondrial DNA depletion syndrome 11, 615084;Disorders of mitochondrial DNA maintenance and integrity False 3 100;0;0 30.556 False ENSG00000125871 ENSG00000125871 HGNC:16205 MGME1 gene MGME1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Disorders of mitochondrial DNA maintenance and integrity;Mitochondrial DNA depletion syndrome 11, 615084 False 3 100;0;0 30.556 True ENSG00000125871 ENSG00000125871 HGNC:16205 MICU1 gene MICU1 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Myopathy with extrapyramidal signs 615673 24336167;29721912 False 3 100;0;0 30.556 False ENSG00000107745 ENSG00000107745 HGNC:1530 MICU1 gene MICU1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MYOPATHY WITH EXTRAPYRAMIDAL SIGNS 24336167 False 3 33;67;0 30.556 False ENSG00000107745 ENSG00000107745 HGNC:1530 MICU1 gene MICU1 Expert Review Green;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Myopathy with extrapyramidal signs 615673 24336167;29721912 False 3 100;0;0 30.556 False ENSG00000107745 ENSG00000107745 HGNC:1530 MID1 gene MID1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Opitz GBBB syndrome, type I, 300000;OPITZ G/BBB SYNDROME, X-LINKED False 3 100;0;0 30.556 False ENSG00000101871 ENSG00000101871 HGNC:7095 MINPP1 gene MINPP1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pontocerebellar hypoplasia 33257696;33168985 False 3 100;0;0 30.556 False ENSG00000107789 ENSG00000107789 HGNC:7102 MIPEP gene MIPEP Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 31, 617228 27799064 False 3 100;0;0 30.556 False ENSG00000027001 ENSG00000027001 HGNC:7104 MIPEP gene MIPEP Expert Review Green;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 31, 617228 27799064 False 3 100;0;0 30.556 False ENSG00000027001 ENSG00000027001 HGNC:7104 MKKS gene MKKS Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal McKusick-Kaufman syndrome, 236700Bardet-Biedl syndrome 6, 209900;MCKUSICK-KAUFMAN SYNDROME (MKKS) False 3 100;0;0 30.556 False ENSG00000125863 ENSG00000125863 HGNC:7108 MKS1 gene MKS1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MECKEL SYNDROME TYPE 1 (MKS1) 17377820;16415886 False 3 33;67;0 30.556 False ENSG00000011143 ENSG00000011143 HGNC:7121 MLC1 gene MLC1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal LEUKOENCEPHALOPATHY MEGALENCEPHALIC WITH SUBCORTICAL CYSTS (MLC) 11254442;11935341;21624973;12189496;14615938 False 3 100;0;0 30.556 False ENSG00000100427 ENSG00000100427 HGNC:17082 MLC1 gene MLC1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Megalencephalic leukoencephalopathy with subcortical cysts (MLC);General Leukodystrophy & Mitochondrial Leukoencephalopathy 25655951 False 3 0;0;0 30.556 False ENSG00000100427 ENSG00000100427 HGNC:17082 MLYCD gene MLYCD Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Malonyl-CoA decarboxylase deficiency, 248360;MALONYL-COA DECARBOXYLASE DEFICIENCY False 3 100;0;0 30.556 False ENSG00000103150 ENSG00000103150 HGNC:7150 MLYCD gene MLYCD London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Malonyl-CoA decarboxylase deficiency;malonic aciduria;Malonyl-CoA decarboxylase deficiency (Organic acidurias);3.5.1. Malonyl CoA decarboxylase deficiency Other disorders of fatty acid and ketone body metabolism) 27604308 False 3 0;0;0 30.556 False ENSG00000103150 ENSG00000103150 HGNC:7150 MMAA gene MMAA Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Methylmalonic aciduria, vitamin B12-responsive, 251100;METHYLMALONIC ACIDURIA TYPE CBLA False 3 100;0;0 30.556 False ENSG00000151611 ENSG00000151611 HGNC:18871 MMAA gene MMAA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Methylmalonic aciduria, vitamin B12-responsive 251100;Defect in adenosylcobalamin synthesis-cbl A (Disorders of cobalamin absorption, transport and metabolism) 27604308 False 3 0;0;0 30.556 False ENSG00000151611 ENSG00000151611 HGNC:18871 MMAB gene MMAB London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Defect in adenosylcobalamin synthesis-cbl B (Disorders of cobalamin absorption, transport and metabolism);Methylmalonic aciduria, vitamin B12-responsive, due to defect in synthesis of adenosylcobalamin, cblB complementation type 251110 27604308 False 3 0;0;0 30.556 False ENSG00000139428 ENSG00000139428 HGNC:19331 MMAB gene MMAB Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal METHYLMALONIC ACIDURIA TYPE CBLB 12471062 False 3 100;0;0 30.556 False ENSG00000139428 ENSG00000139428 HGNC:19331 MMACHC gene MMACHC London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Methylmalonic aciduria and homocystinuria, cblC type, 277400 27604308 False 3 0;0;0 30.556 False ENSG00000132763 ENSG00000132763 HGNC:24525 MMACHC gene MMACHC Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Methylmalonic aciduria and homocystinuria, cblC type, 277400;METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, CBLC TYPE False 3 100;0;0 30.556 False ENSG00000132763 ENSG00000132763 HGNC:24525 MMADHC gene MMADHC London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Homocystinuria, cblD type, variant 1 False 3 0;0;0 30.556 False ENSG00000168288 ENSG00000168288 HGNC:25221 MMADHC gene MMADHC Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Homocystinuria, cblD type, variant 1, 277410Methylmalonic aciduria, cblD type, variant 2, 277410Methylmalonic aciduria and homocystinuria, cblD type, 277410;METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA TYPE CBLD (MMADHC) False 3 100;0;0 30.556 False ENSG00000168288 ENSG00000168288 HGNC:25221 MN1 gene MN1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown CEBALID syndrome, OMIM:618774;CEBALID syndrome, MONDO:0032908 31834374;31839203;15870292 False 3 100;0;0 30.556 False ENSG00000169184 ENSG00000169184 HGNC:7180 MOCS1 gene MOCS1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Molybdenum cofactor deficiency A 252150 27604308;9731530;12754701 False 3 0;0;0 30.556 False ENSG00000124615 ENSG00000124615 HGNC:7190 MOCS1 gene MOCS1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Molybdenum cofactor deficiency, type A, 252150;MOLYBDENUM COFACTOR DEFICIENCY False 3 100;0;0 30.556 False ENSG00000124615 ENSG00000124615 HGNC:7190 MOCS2 gene MOCS2 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Molybdenum cofactor deficiency B 252160 27604308;10053004;12754701;12732628;11746050;16021469;16737835 False 3 0;0;0 30.556 False ENSG00000164172 ENSG00000164172 HGNC:7193 MOCS2 gene MOCS2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Molybdenum cofactor deficiency, type B, 252150;MOLYBDENUM COFACTOR DEFICIENCY False 3 100;0;0 30.556 False ENSG00000164172 ENSG00000164172 HGNC:7193 MOGS gene MOGS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIb 606056;MOGS-CDG (Disorders of protein N-glycosylation);Congenital disorder of glycosylation, type IIb, 606056;(MOGS-CDG (Disorders of protein N-glycosylation)) 20301507;26805780;24716661;4716661 False 3 100;0;0 30.556 False ENSG00000115275 ENSG00000115275 HGNC:24862 MOGS gene MOGS Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIb, 606056 24716661;20301507 False 3 0;100;0 30.556 False ENSG00000115275 ENSG00000115275 HGNC:24862 MORC2 gene MORC2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Charcot-Marie-Tooth disease, axonal, type 2Z, OMIM:616688;Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy, OMIM:619090 32693025 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000133422 ENSG00000133422 HGNC:23573 MPC1 gene MPC1 Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial pyruvate carrier deficiency, OMIM:614741 22628558;27176894;27835892 False 3 100;0;0 30.556 False ENSG00000060762 ENSG00000060762 HGNC:21606 MPC1 gene MPC1 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial pyruvate carrier deficiency, OMIM:614741 27176894;22628558;27835892 False 3 100;0;0 30.556 False ENSG00000060762 ENSG00000060762 HGNC:21606 MPDU1 gene MPDU1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type If, OMIM:609180 False 3 100;0;0 30.556 False ENSG00000129255 ENSG00000129255 HGNC:7207 MPDU1 gene MPDU1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type If, OMIM:609180;Lec35 deficiency (Disorders of multiple glycosylation and other glycosylation pathways) 27604308 False 3 0;0;0 30.556 False ENSG00000129255 ENSG00000129255 HGNC:7207 MPI gene MPI London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Ib, OMIM:602579;MPI-CDG, MONDO:0011257;Phosphomannose isomerase deficiency (Disorders of protein N-glycosylation) 12414827;9585601;10980531;33098580;33204592;32905087;32266963;30242110 False 3 0;0;0 30.556 False ENSG00000178802 ENSG00000178802 HGNC:7216 MPLKIP gene MPLKIP Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Trichothiodystrophy, nonphotosensitive 1, 234050;TRICHOTHIODYSTROPHY NON-PHOTOSENSITIVE TYPE 1 False 3 100;0;0 30.556 False ENSG00000168303 ENSG00000168303 HGNC:16002 MPP5 gene MPP5 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Global developmental delay;Intellectual disability;Delayed speech and language development;Developmental regression;Behavioral abnormality 33073849 False 3 100;0;0 30.556 False ENSG00000072415 ENSG00000072415 HGNC:18669 MPV17 gene MPV17 Victorian Clinical Genetics Services;UKGTN;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of mitochondrial DNA maintenance and integrity;Mitochondrial DNA depletion syndrome 6 (hepatocerebral type), 256810 -3;Mitochondrial DNA Depletion Syndrome False 3 100;0;0 30.556 False ENSG00000115204 ENSG00000115204 HGNC:7224 MPV17 gene MPV17 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA Depletion Syndrome;Disorders of mitochondrial DNA maintenance and integrity;Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Mitochondrial DNA depletion syndrome 6 (hepatocerebral type), 256810 -3 27604308 False 3 100;0;0 30.556 False ENSG00000115204 ENSG00000115204 HGNC:7224 MRM2 gene MRM2 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Mitochondrial DNA depletion syndrome 17, OMIM:618567 28973171;36002240 False 3 50;50;0 30.556 False ENSG00000122687 ENSG00000122687 HGNC:16352 MRM2 gene MRM2 NHS GMS;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Mitochondrial DNA depletion syndrome 17, OMIM:618567 28973171;36002240 False 3 100;0;0 30.556 False ENSG00000122687 ENSG00000122687 HGNC:16352 MRPL3 gene MRPL3 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 9, 614582 27815843;21786366 False 3 50;50;0 30.556 False ENSG00000114686 ENSG00000114686 HGNC:10379 MRPL3 gene MRPL3 Expert Review Green;Expert Review Green;NHS GMS;London North GLH;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 9 614582 27815843;21786366 False 3 50;50;0 30.556 False ENSG00000114686 ENSG00000114686 HGNC:10379 MRPL39 gene MRPL39 Expert Review Green;Literature;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 59, OMIM:620646 37133451 False 3 100;0;0 30.556 False ENSG00000154719 ENSG00000154719 HGNC:14027 MRPL39 gene MRPL39 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 59, OMIM:620646 37133451 False 3 100;0;0 30.556 False ENSG00000154719 ENSG00000154719 HGNC:14027 MRPL44 gene MRPL44 Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);?Combined oxidative phosphorylation deficiency 16, 615395 25797485;23315540 False 3 100;0;0 30.556 False ENSG00000135900 ENSG00000135900 HGNC:16650 MRPL44 gene MRPL44 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Combined oxidative phosphorylation deficiency 16, 615395;Multiple respiratory chain complex deficiencies (disorders of protein synthesis) 25797485;23315540 False 3 100;0;0 30.556 False ENSG00000135900 ENSG00000135900 HGNC:16650 MRPL49 gene MRPL49 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 60, OMIM:621195;combined oxidative phosphorylation deficiency, MONDO:0000732 40043708 False 3 100;0;0 30.556 True ENSG00000149792 ENSG00000149792 HGNC:1176 MRPL49 gene MRPL49 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 60, OMIM:621195;combined oxidative phosphorylation deficiency, MONDO:0000732 40043708 False 3 100;0;0 30.556 False ENSG00000149792 ENSG00000149792 HGNC:1176 MRPL49 gene MRPL49 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 60, OMIM:621195;combined oxidative phosphorylation deficiency, MONDO:0000732 40043708 False 3 100;0;0 30.556 False ENSG00000149792 ENSG00000149792 HGNC:1176 MRPS2 gene MRPS2 Expert Review Green;NHS GMS;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 36 617950 29576219 False 3 0;100;0 30.556 False ENSG00000122140 ENSG00000122140 HGNC:14495 MRPS2 gene MRPS2 Expert Review Green;Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 36 617950;No OMIM phenotype 29576219 False 3 0;100;0 30.556 False ENSG00000122140 ENSG00000122140 HGNC:14495 MRPS22 gene MRPS22 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 5, 611719;COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 5 False 3 100;0;0 30.556 False ENSG00000175110 ENSG00000175110 HGNC:14508 MRPS22 gene MRPS22 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 5, 611719;Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Multiple respiratory chain complex deficiencies (disorders of protein synthesis) 27604308 False 3 100;0;0 30.556 False ENSG00000175110 ENSG00000175110 HGNC:14508 MRPS22 gene MRPS22 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 5, 611719 False 3 100;0;0 30.556 True ENSG00000175110 ENSG00000175110 HGNC:14508 MRPS34 gene MRPS34 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 32 617664 28777931 False 3 100;0;0 30.556 True ENSG00000074071 ENSG00000074071 HGNC:16618 MRPS34 gene MRPS34 Literature;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidativephosphorylation deficiency 32, 617664 30914295;28777931 False 3 0;0;0 30.556 False ENSG00000074071 ENSG00000074071 HGNC:16618 MRPS34 gene MRPS34 Expert Review Green;Literature;Expert Review;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 32 617664 28777931 False 3 100;0;0 30.556 False ENSG00000074071 ENSG00000074071 HGNC:16618 MSL2 gene MSL2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Karayol-Borroto-Haghshenas neurodevelopmental syndrome, OMIM:620985 31332282;33057194;38702431;38815585 False 3 75;25;0 30.556 False ENSG00000174579 ENSG00000174579 HGNC:25544 MSL3 gene MSL3 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Muscular hypotonia;Feeding difficulties;Neurodevelopmental delay;Intellectual disability;Basilicata-Akhtar syndrome, 301032 26350204;19377476;28135719;25529582;30224647 False 3 50;17;33 30.556 False ENSG00000005302 ENSG00000005302 HGNC:7370 MSMO1 gene MSMO1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sterol-C4-methyl oxidase deficiency (Disorders of sterol biosynthesis);Microcephaly, congenital cataract, and psoriasiform dermatitis, OMIM:616834;Microcephaly-congenital cataract-psoriasiform dermatitis syndrome, MONDO:0014793 27604308 False 3 100;0;0 30.556 False ENSG00000052802 ENSG00000052802 HGNC:10545 MSMO1 gene MSMO1 Expert Review Green;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly, congenital cataract, and psoriasiform dermatitis, OMIM:616834;Microcephaly-congenital cataract-psoriasiform dermatitis syndrome, MONDO:0014793 False 3 100;0;0 30.556 False ENSG00000052802 ENSG00000052802 HGNC:10545 MSTO1 gene MSTO1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Myopathy, mitochondrial, and ataxia OMIM:617675;mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome MONDO:0044714 28554942;28544275;29339779;37431817 False 3 0;0;0 30.556 False ENSG00000125459 ENSG00000125459 HGNC:29678 MSTO1 gene MSTO1 NHS GMS;Expert list;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Myopathy, mitochondrial, and ataxia OMIM:617675;mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome MONDO:0044714 28554942;28544275;37431817 False 3 0;0;0 30.556 False ENSG00000125459 ENSG00000125459 HGNC:29678 MT-ATP6 gene MT-ATP6 Expert Review Green;Emory Genetics Laboratory;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000198899 ENSG00000198899 HGNC:7414 MT-ATP6 gene MT-ATP6 Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000198899 ENSG00000198899 HGNC:7414 MT-ATP8 gene MT-ATP8 Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL Mitochondrial cardiomyopathy complex V (ATP synthase) deficiency False 3 100;0;0 30.556 False ENSG00000228253 ENSG00000228253 HGNC:7415 MT-ATP8 gene MT-ATP8 Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL Mitochondrial cardiomyopathy complex V (ATP synthase) deficiency 24153443;20207608;32858252;33340416;32858252;19759059;22919063 False 3 75;25;0 30.556 True ENSG00000228253 ENSG00000228253 HGNC:7415 MT-CO1 gene MT-CO1 Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL LEBER OPTIC ATROPHY;SIDEROBLASTIC ANEMIA, ACQUIRED IDIOPATHIC;CYTOCHROME c OXIDASE DEFICIENCY;MYOGLOBINURIA, RECURRENT;CYTOCHROME c OXIDASE I DEFICIENCY False 3 100;0;0 30.556 True ENSG00000198804 ENSG00000198804 HGNC:7419 MT-CO1 gene MT-CO1 Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL CYTOCHROME c OXIDASE I DEFICIENCY;SIDEROBLASTIC ANEMIA, ACQUIRED IDIOPATHIC;LEBER OPTIC ATROPHY;MYOGLOBINURIA, RECURRENT;CYTOCHROME c OXIDASE DEFICIENCY False 3 100;0;0 30.556 False ENSG00000198804 ENSG00000198804 HGNC:7419 MT-CO2 gene MT-CO2 Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL CYTOCHROME c OXIDASE DEFICIENCY False 3 100;0;0 30.556 False ENSG00000198712 ENSG00000198712 HGNC:7421 MT-CO2 gene MT-CO2 Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL CYTOCHROME c OXIDASE DEFICIENCY False 3 100;0;0 30.556 True ENSG00000198712 ENSG00000198712 HGNC:7421 MT-CO3 gene MT-CO3 Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL LEBER OPTIC ATROPHY;MITOCHONDRIAL COMPLEX IV DEFICIENCY;SEIZURES AND LACTIC ACIDOSIS False 3 100;0;0 30.556 True ENSG00000198938 ENSG00000198938 HGNC:7422 MT-CO3 gene MT-CO3 Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL LEBER OPTIC ATROPHY;SEIZURES AND LACTIC ACIDOSIS;MITOCHONDRIAL COMPLEX IV DEFICIENCY none False 3 100;0;0 30.556 False ENSG00000198938 ENSG00000198938 HGNC:7422 MT-CYB gene MT-CYB Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL ENCEPHALOMYOPATHY, MITOCHONDRIAL;CARDIOMYOPATHY, INFANTILE HISTIOCYTOID;MULTISYSTEM DISORDER;EXERCISE INTOLERANCE;PARKINSONISM/MELAS OVERLAP SYNDROME;EXERCISE INTOLERANCE, CARDIOMYOPATHY, AND SEPTOOPTIC DYSPLASIA;LEBER OPTIC ATROPHY False 3 100;0;0 30.556 False ENSG00000198727 ENSG00000198727 HGNC:7427 MT-CYB gene MT-CYB Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL LEBER OPTIC ATROPHY;ENCEPHALOMYOPATHY, MITOCHONDRIAL;MULTISYSTEM DISORDER;EXERCISE INTOLERANCE;CARDIOMYOPATHY, INFANTILE HISTIOCYTOID;EXERCISE INTOLERANCE, CARDIOMYOPATHY, AND SEPTOOPTIC DYSPLASIA;PARKINSONISM/MELAS OVERLAP SYNDROME False 3 100;0;0 30.556 True ENSG00000198727 ENSG00000198727 HGNC:7427 MTFMT gene MTFMT Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 15 OMIM:614947;combined oxidative phosphorylation defect type 15 MONDO:0013987;Mitochondrial complex I deficiency, nuclear type 27 OMIM:618248;mitochondrial complex 1 deficiency, nuclear type 27 MONDO:0032631 27564080;21907147;24461907;23499752 False 3 100;0;0 30.556 False ENSG00000103707 ENSG00000103707 HGNC:29666 MTFMT gene MTFMT Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 15, OMIM:614947 21907147;24461907;27564080 False 3 0;0;0 30.556 False ENSG00000103707 ENSG00000103707 HGNC:29666 MTFMT gene MTFMT Expert Review Green;Expert Review Green;London North GLH;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 15 OMIM:614947;combined oxidative phosphorylation defect type 15 MONDO:0013987;Mitochondrial complex I deficiency, nuclear type 27 OMIM:618248;mitochondrial complex 1 deficiency, nuclear type 27 MONDO:0032631 21907147;27564080;23499752;24461907 False 3 100;0;0 30.556 False ENSG00000103707 ENSG00000103707 HGNC:29666 MTFMT gene MTFMT Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 15 OMIM:614947;combined oxidative phosphorylation defect type 15 MONDO:0013987;Mitochondrial complex I deficiency, nuclear type 27 OMIM:618248;mitochondrial complex 1 deficiency, nuclear type 27 MONDO:0032631 24461907;23499752;22499348 False 3 100;0;0 30.556 False ENSG00000103707 ENSG00000103707 HGNC:29666 MTHFR gene MTHFR London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Methylenetetrahydrofolate reductase deficiency (Disorders of folate metabolism and transport);Homocystinuria due to MTHFR deficiency 27604308 False 3 0;0;0 30.556 False ENSG00000177000 ENSG00000177000 HGNC:7436 MTHFR gene MTHFR Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal METHYLENETETRAHYDROFOLATE REDUCTASE DEFICIENCY (MTHFRD) 0 False 3 33;67;0 30.556 False ENSG00000177000 ENSG00000177000 HGNC:7436 MTHFS gene MTHFS Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination, 618367 30031689;31844630;22303332;https://doi.org/10.1007/978-3-642-40337-8_10 False 3 100;0;0 30.556 False ENSG00000136371 ENSG00000136371 HGNC:7437 MT-ND1 gene MT-ND1 Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL LEBER OPTIC ATROPHY;SUDDEN INFANT DEATH SYNDROME;MITOCHONDRIAL COMPLEX I DEFICIENCY;DYSTONIA, ADULT-ONSET;MELAS SYNDROME;DEAFNESS, NONSYNDROMIC SENSORINEURAL, MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000198888 ENSG00000198888 HGNC:7455 MT-ND1 gene MT-ND1 Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL MELAS SYNDROME;MITOCHONDRIAL COMPLEX I DEFICIENCY;LEBER OPTIC ATROPHY;DYSTONIA, ADULT-ONSET;DEAFNESS, NONSYNDROMIC SENSORINEURAL, MITOCHONDRIAL;SUDDEN INFANT DEATH SYNDROME False 3 100;0;0 30.556 False ENSG00000198888 ENSG00000198888 HGNC:7455 MT-ND2 gene MT-ND2 Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL MITOCHONDRIAL COMPLEX I DEFICIENCY;LEBER OPTIC ATROPHY;LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY False 3 100;0;0 30.556 False ENSG00000198763 ENSG00000198763 HGNC:7456 MT-ND2 gene MT-ND2 Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL LEBER OPTIC ATROPHY;MITOCHONDRIAL COMPLEX I DEFICIENCY;LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY False 3 100;0;0 30.556 True ENSG00000198763 ENSG00000198763 HGNC:7456 MT-ND3 gene MT-ND3 Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL MITOCHONDRIAL COMPLEX I DEFICIENCY;LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY False 3 100;0;0 30.556 True ENSG00000198840 ENSG00000198840 HGNC:7458 MT-ND3 gene MT-ND3 Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL MITOCHONDRIAL COMPLEX I DEFICIENCY;LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY False 3 100;0;0 30.556 False ENSG00000198840 ENSG00000198840 HGNC:7458 MT-ND4 gene MT-ND4 Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL MELAS SYNDROME;LEBER OPTIC ATROPHY AND DYSTONIA;LEBER OPTIC ATROPHY;MITOCHONDRIAL COMPLEX I DEFICIENCY False 3 100;0;0 30.556 False ENSG00000198886 ENSG00000198886 HGNC:7459 MT-ND4 gene MT-ND4 Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL LEBER OPTIC ATROPHY;MELAS SYNDROME;LEBER OPTIC ATROPHY AND DYSTONIA;MITOCHONDRIAL COMPLEX I DEFICIENCY False 3 100;0;0 30.556 True ENSG00000198886 ENSG00000198886 HGNC:7459 MT-ND4L gene MT-ND4L Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL LEBER OPTIC ATROPHY False 3 100;0;0 30.556 True ENSG00000212907 ENSG00000212907 HGNC:7460 MT-ND4L gene MT-ND4L Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL LEBER OPTIC ATROPHY False 3 100;0;0 30.556 False ENSG00000212907 ENSG00000212907 HGNC:7460 MT-ND5 gene MT-ND5 Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL MELAS SYNDROME;LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY;LEBER OPTIC ATROPHY;MERRF SYNDROME False 3 100;0;0 30.556 False ENSG00000198786 ENSG00000198786 HGNC:7461 MT-ND5 gene MT-ND5 Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL LEBER OPTIC ATROPHY;LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY;MELAS SYNDROME;LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY;MERRF SYNDROME False 3 100;0;0 30.556 False ENSG00000198786 ENSG00000198786 HGNC:7461 MT-ND6 gene MT-ND6 Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL LEBER OPTIC ATROPHY;LEBER OPTIC ATROPHY AND DYSTONIA;LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY;MELAS SYNDROME;STRIATAL NECROSIS, BILATERAL, WITH DYSTONIA False 3 100;0;0 30.556 True ENSG00000198695 ENSG00000198695 HGNC:7462 MT-ND6 gene MT-ND6 Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL MELAS SYNDROME;STRIATAL NECROSIS, BILATERAL, WITH DYSTONIA;LEBER OPTIC ATROPHY AND DYSTONIA;LEBER OPTIC ATROPHY;LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY False 3 100;0;0 30.556 False ENSG00000198695 ENSG00000198695 HGNC:7462 MTO1 gene MTO1 Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 10, 614702 29331171 False 3 100;0;0 30.556 False ENSG00000135297 ENSG00000135297 HGNC:19261 MTO1 gene MTO1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 10, 614702;Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only));infantile hypertrophic cardiomyopathy and lactic acidosis. 27604308 False 3 100;0;0 30.556 False ENSG00000135297 ENSG00000135297 HGNC:19261 MTO1 gene MTO1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 10, 614702;infantile hypertrophic cardiomyopathy and lactic acidosis. False 3 100;0;0 30.556 True ENSG00000135297 ENSG00000135297 HGNC:19261 MTOR gene MTOR Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Smith-Kingsmore syndrome, 616638;Intellectual Disability;Focal cortical dysplasia, type II, somatic 607341 26542245;27830187;25851998;28892148;https://doi.org/10.4137/jge.s12583;27159400 False 3 50;0;50 30.556 False Other - please provide details in the comments ENSG00000198793 ENSG00000198793 HGNC:3942 MTPAP gene MTPAP Expert Review Green;Expert Review Green;London North GLH;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Spastic ataxia 4, autosomal recessive 613672 27959697;26319014;25008111;20970105;27391121 False 3 100;0;0 30.556 False ENSG00000107951 ENSG00000107951 HGNC:25532 MTPAP gene MTPAP Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Spastic ataxia 4, autosomal recessive 613672 20970105;25008111;26319014;27391121;27959697 False 3 100;0;0 30.556 False ENSG00000107951 ENSG00000107951 HGNC:25532 MTR gene MTR Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Homocystinuria-megaloblastic anemia, cblG complementation type, 250940;{Neural tube defects, folate-sensitive, susceptibility to}, 601634;METHYLCOBALAMIN DEFICIENCY TYPE G (CBLG) False 3 100;0;0 30.556 False ENSG00000116984 ENSG00000116984 HGNC:7468 MTR gene MTR London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Homocystinuria-megaloblastic anemia, cblG complementation type 27604308 False 3 0;0;0 30.556 False ENSG00000116984 ENSG00000116984 HGNC:7468 MT-RNR1 gene MT-RNR1 Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL DEAFNESS, AMINOGLYCOSIDE-INDUCED;DEAFNESS, NONSYNDROMIC SENSORINEURAL, MITOCHONDRIAL;AUDITORY NEUROPATHY;CARDIOMYOPATHY, RESTRICTIVE False 3 100;0;0 30.556 False ENSG00000211459 ENSG00000211459 HGNC:7470 MT-RNR1 gene MT-RNR1 Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL DEAFNESS, AMINOGLYCOSIDE-INDUCED;DEAFNESS, NONSYNDROMIC SENSORINEURAL, MITOCHONDRIAL;CARDIOMYOPATHY, RESTRICTIVE;AUDITORY NEUROPATHY False 3 100;0;0 30.556 True ENSG00000211459 ENSG00000211459 HGNC:7470 MTRR gene MTRR London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Homocystinuria-megaloblastic anemia, cbl E type 27604308 False 3 0;0;0 30.556 False ENSG00000124275 ENSG00000124275 HGNC:7473 MTRR gene MTRR Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Homocystinuria-megaloblastic anemia, cbl E type, 236270{Neural tube defects, folate-sensitive, susceptibility to}, 601634;HOMOCYSTINURIA-MEGALOBLASTIC ANEMIA, CBL E TYPE False 3 100;0;0 30.556 False ENSG00000124275 ENSG00000124275 HGNC:7473 MTSS1L gene MTSS1L Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual developmental disorder with ocular anomalies and distinctive facial features, OMIM:620086 36067766 False 3 100;0;0 30.556 False ENSG00000132613 ENSG00000132613 HGNC:25094 MT-TA gene MT-TA Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL MYOTONIC DYSTROPHY-LIKE MYOPATHY;MITOCHONDRIAL MYOPATHY False 3 100;0;0 30.556 True ENSG00000210127 ENSG00000210127 HGNC:7475 MT-TA gene MT-TA Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL MITOCHONDRIAL MYOPATHY;MYOTONIC DYSTROPHY-LIKE MYOPATHY False 3 100;0;0 30.556 False ENSG00000210127 ENSG00000210127 HGNC:7475 MT-TC gene MT-TC Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL MELAS SYNDROME;DYSTONIA, MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000210140 ENSG00000210140 HGNC:7477 MT-TC gene MT-TC Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL MELAS SYNDROME;DYSTONIA, MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000210140 ENSG00000210140 HGNC:7477 MT-TD gene MT-TD Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL MITOCHONDRIAL MYOPATHY, ISOLATED False 3 100;0;0 30.556 False ENSG00000210154 ENSG00000210154 HGNC:7478 MT-TD gene MT-TD Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL MITOCHONDRIAL MYOPATHY, ISOLATED False 3 100;0;0 30.556 False ENSG00000210154 ENSG00000210154 HGNC:7478 MT-TE gene MT-TE Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL MYOPATHY, MITOCHONDRIAL, WITH DIABETES MELLITUS;DIABETES AND DEAFNESS, MATERNALLY INHERITED;MITOCHONDRIAL MYOPATHY, INFANTILE, TRANSIENT False 3 100;0;0 30.556 False ENSG00000210194 ENSG00000210194 HGNC:7479 MT-TE gene MT-TE Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL MYOPATHY, MITOCHONDRIAL, WITH DIABETES MELLITUS;DIABETES AND DEAFNESS, MATERNALLY INHERITED;MITOCHONDRIAL MYOPATHY, INFANTILE, TRANSIENT False 3 100;0;0 30.556 True ENSG00000210194 ENSG00000210194 HGNC:7479 MT-TF gene MT-TF Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000210049 ENSG00000210049 HGNC:7481 MT-TF gene MT-TF Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000210049 ENSG00000210049 HGNC:7481 MT-TG gene MT-TG Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000210164 ENSG00000210164 HGNC:7486 MT-TG gene MT-TG Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000210164 ENSG00000210164 HGNC:7486 MT-TH gene MT-TH Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000210176 ENSG00000210176 HGNC:7487 MT-TH gene MT-TH Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000210176 ENSG00000210176 HGNC:7487 MT-TI gene MT-TI Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL familial hypertrophic cardiomyopathy, MONDO:0024573;familial dilated cardiomyopathy, MONDO:0016333 False 3 100;0;0 30.556 False ENSG00000210100 ENSG00000210100 HGNC:7488 MT-TI gene MT-TI Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL familial hypertrophic cardiomyopathy, MONDO:0024573;familial dilated cardiomyopathy, MONDO:0016333 False 3 100;0;0 30.556 True ENSG00000210100 ENSG00000210100 HGNC:7488 MT-TK gene MT-TK Expert Review Green;Emory Genetics Laboratory;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000210156 ENSG00000210156 HGNC:7489 MT-TK gene MT-TK Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000210156 ENSG00000210156 HGNC:7489 MT-TL1 gene MT-TL1 Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000209082 ENSG00000209082 HGNC:7490 MT-TL1 gene MT-TL1 Expert Review Green;Emory Genetics Laboratory;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000209082 ENSG00000209082 HGNC:7490 MT-TL2 gene MT-TL2 Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000210191 ENSG00000210191 HGNC:7491 MT-TL2 gene MT-TL2 Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000210191 ENSG00000210191 HGNC:7491 MT-TM gene MT-TM Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000210112 ENSG00000210112 HGNC:7492 MT-TM gene MT-TM Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000210112 ENSG00000210112 HGNC:7492 MT-TN gene MT-TN Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000210135 ENSG00000210135 HGNC:7493 MT-TN gene MT-TN Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000210135 ENSG00000210135 HGNC:7493 MTTP gene MTTP London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Abetalipoproteinemia, 200100;(ACANTHOCYTOSIS, BASSEN-KORNZWEIG SYNDROME, MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN DEFICIENCY, MTP DEFICIENCY);Familial abetalipoproteinaemia (Inherited hypolipidaemias) 27604308 False 3 100;0;0 30.556 False ENSG00000138823 ENSG00000138823 HGNC:7467 MT-TP gene MT-TP Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000210196 ENSG00000210196 HGNC:7494 MT-TP gene MT-TP Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000210196 ENSG00000210196 HGNC:7494 MT-TQ gene MT-TQ Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000210107 ENSG00000210107 HGNC:7495 MT-TQ gene MT-TQ Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000210107 ENSG00000210107 HGNC:7495 MT-TR gene MT-TR Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000210174 ENSG00000210174 HGNC:7496 MT-TR gene MT-TR Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000210174 ENSG00000210174 HGNC:7496 MT-TS1 gene MT-TS1 Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000210151 ENSG00000210151 HGNC:7497 MT-TS1 gene MT-TS1 Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000210151 ENSG00000210151 HGNC:7497 MT-TS2 gene MT-TS2 Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000210184 ENSG00000210184 HGNC:7498 MT-TS2 gene MT-TS2 Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000210184 ENSG00000210184 HGNC:7498 MT-TT gene MT-TT Expert Review Green;NHS GMS;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL mitochondrial disease, MONDO:0044970;Leber optic atrophy, OMIM:535000;myoclonic epilepsy associated with ragged-red fibers, OMIM:545000;fatal infantile respiratory enzyme deficiency;Inherited Diabetes Mellitus;adult onset mild myopathy 32083134;8769114;9367299;1645537;8511015;22638997;29760464;30236074;28187756;35808913 False 3 75;25;0 30.556 False ENSG00000210195 ENSG00000210195 HGNC:7499 MT-TT gene MT-TT Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology MITOCHONDRIAL mitochondrial disease, MONDO:0044970;Leber optic atrophy, OMIM:535000;myoclonic epilepsy associated with ragged-red fibers, OMIM:545000;fatal infantile respiratory enzyme deficiency;Inherited Diabetes Mellitus;adult onset mild myopathy 32083134;8769114;9367299;1645537;8511015;22638997;29760464;30236074;28187756;35808913 False 3 75;25;0 30.556 False ENSG00000210195 ENSG00000210195 HGNC:7499 MT-TV gene MT-TV Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000210077 ENSG00000210077 HGNC:7500 MT-TV gene MT-TV Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000210077 ENSG00000210077 HGNC:7500 MT-TW gene MT-TW Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000210117 ENSG00000210117 HGNC:7501 MT-TW gene MT-TW Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000210117 ENSG00000210117 HGNC:7501 MT-TY gene MT-TY Expert Review Green Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 False ENSG00000210144 ENSG00000210144 HGNC:7502 MT-TY gene MT-TY Expert Review Green;UKGTN Childhood onset leukodystrophy Neurology MITOCHONDRIAL False 3 100;0;0 30.556 True ENSG00000210144 ENSG00000210144 HGNC:7502 MUT gene MUT Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Methylmalonic aciduria, mut(0) type, 251000;METHYLMALONIC ACIDURIA TYPE MUT False 3 100;0;0 30.556 False ENSG00000146085 ENSG00000146085 HGNC:7526 MUT gene MUT London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections.;Methylmalonic aciduria, mut(0) type 251000;Methylmalonyl-CoA mutase deficiency (Organic acidurias) 27604308 False 3 0;0;0 30.556 False ENSG00000146085 ENSG00000146085 HGNC:7526 MVK gene MVK Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Hyper-IgD syndrome, OMIM:260920;Mevalonic aciduria, OMIM:610377;Porokeratosis 3, multiple types, OMIM:175900 27604308;10417275;16835861;10369261;16435210;26202976 False 3 0;0;0 30.556 False ENSG00000110921 ENSG00000110921 HGNC:7530 MVK gene MVK Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mevalonic aciduria, OMIM:610377 29451047;12563048;10401001 False 3 0;0;100 30.556 False ENSG00000110921 ENSG00000110921 HGNC:7530 MYCN gene MYCN Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Feingold syndrome 1, OMIM:164280 37710961;30573562;21224895;8470948;16906565;18671284;15821734;18470948 False 3 100;0;0 30.556 False ENSG00000134323 ENSG00000134323 HGNC:7559 MYH10 gene MYH10 NHS GMS;Expert Review Green;Gene2Phenotype Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071;MYH10-related Multiple congenital anomalies 25356899;25003005;35980381 False 3 67;0;33 30.556 False ENSG00000133026 ENSG00000133026 HGNC:7568 MYO5A gene MYO5A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Griscelli syndrome, type 1, 214450;ELEJALDE SYNDROME (ELEJAS) False 3 100;0;0 30.556 False ENSG00000197535 ENSG00000197535 HGNC:7602 MYT1L gene MYT1L Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Mental retardation, autosomal dominant 39, 616521;MRD39;Intellectual disability;obesity 23033978;25529582;28859103;29293472;28470180;25232846;26240977 False 3 50;0;50 30.556 False ENSG00000186487 ENSG00000186487 HGNC:7623 NAA10 gene NAA10 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) N-terminal acetyltransferase deficiency, 300855;NONPECIFIC SEVERE ID False 3 100;0;0 30.556 False ENSG00000102030 ENSG00000102030 HGNC:18704 NAA15 gene NAA15 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Mental retardation, autosomal dominant 50, 617787;Intellectual disability 29656860;28191889 False 3 100;0;0 30.556 False ENSG00000164134 ENSG00000164134 HGNC:30782 NAA20 gene NAA20 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder, autosomal recessive 73, OMIM:619717 34230638;37191084;39814713 False 3 67;33;0 30.556 False ENSG00000173418 ENSG00000173418 HGNC:15908 NAA60 gene NAA60 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Basal ganglia calcification, idiopathic, 9, autosomal recessive, OMIM:620786;basal ganglia calcification, idiopathic, 9, autosomal recessive, MONDO:0968977 38480682 False 3 100;0;0 30.556 False ENSG00000122390 ENSG00000122390 HGNC:25875 NACC1 gene NACC1 Victorian Clinical Genetics Services;Expert Review Green;Other Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination, 617393;profound developmental delay 28132692 False 3 100;0;0 30.556 False ENSG00000160877 ENSG00000160877 HGNC:20967 NADK2 gene NADK2 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 2,4-dienoyl-CoA reductase deficiency, OMIM:616034 24847004;29388319;27940755 False 3 100;0;0 30.556 False ENSG00000152620 ENSG00000152620 HGNC:26404 NADK2 gene NADK2 Expert Review Green;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 2,4-dienoyl-CoA reductase deficiency, OMIM:616034 24847004;29388319;27940755 False 3 100;0;0 30.556 False ENSG00000152620 ENSG00000152620 HGNC:26404 NAGA gene NAGA Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Schindler disease, type I, 609241Kanzaki disease, 609242Schindler disease, type III, 609241;KANZAKI DISEASE (KANZD) False 3 100;0;0 30.556 False ENSG00000198951 ENSG00000198951 HGNC:7631 NAGA gene NAGA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Kanzaki disease False 3 0;0;0 30.556 False ENSG00000198951 ENSG00000198951 HGNC:7631 NAGLU gene NAGLU Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mucopolysaccharidosis type IIIB (Sanfilippo B), 252920;MUCOPOLYSACCHARIDOSIS TYPE 3B (MPS3B) False 3 100;0;0 30.556 False ENSG00000108784 ENSG00000108784 HGNC:7632 NAGLU gene NAGLU London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mucopolysaccharidosis Type III;Mucopolysaccharidosis, Type III;Mucopolysaccharidosis type IIIB (Sanfilippo B), 252920;MPS IIIB, Sanfilippo B disease (Mucopolysaccharidoses);MUCOPOLYSACCHARIDOSIS TYPE 3B;Mucopolysaccharidosis Type IIIB 27604308 False 3 0;0;0 30.556 False ENSG00000108784 ENSG00000108784 HGNC:7632 NAGS gene NAGS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal N-Acetylglutamate synthetase deficiency (Urea cycle disorders and inherited hyperammonaemias);N-acetylglutamate synthase deficiency 27604308 False 3 0;0;0 30.556 False ENSG00000161653 ENSG00000161653 HGNC:17996 NALCN gene NALCN Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Congenital contractures of the limbs and face, hypotonia, and developmental delay, OMIM:616266;Hypotonia, infantile, with psychomotor retardation and characteristic facies 1, OMIM:615419 False 3 100;0;0 30.556 False ENSG00000102452 ENSG00000102452 HGNC:19082 NANS gene NANS Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spondyloepimetaphyseal dysplasia, Camera-Genevieve type 610442 27213289 False 3 100;0;0 30.556 False ENSG00000095380 ENSG00000095380 HGNC:19237 NAPB gene NAPB Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental and epileptic encephalopathy 107, OMIM:620033 28097321;33189936;26235277;21040848 False 3 100;0;0 30.556 False ENSG00000125814 ENSG00000125814 HGNC:15751 NARS gene NARS Expert Review Green;Literature Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive, OMIM:619091;Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, autosomal dominant, OMIM:619092 32738225;32788587 False 3 100;0;0 30.556 False ENSG00000134440 ENSG00000134440 HGNC:7643 NARS2 gene NARS2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 24 PMID: 25385316;25629079;25807530 False 3 100;0;0 30.556 True ENSG00000137513 ENSG00000137513 HGNC:26274 NARS2 gene NARS2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 24 25629079;25807530;25385316 False 3 100;0;0 30.556 False ENSG00000137513 ENSG00000137513 HGNC:26274 NAV3 gene NAV3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal recessive neurodevelopmental disorder 38977784;39038237;39708122 False 3 100;0;0 30.556 False ENSG00000067798 ENSG00000067798 HGNC:15998 NAXD gene NAXD Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2, OMIM:618321 30576410;33224489;31755961 False 3 100;0;0 30.556 False ENSG00000213995 ENSG00000213995 HGNC:25576 NAXD gene NAXD Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2 618321 29903433;30576410;33224489;31755961 False 3 67;0;33 30.556 False ENSG00000213995 ENSG00000213995 HGNC:25576 NAXD gene NAXD Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2, OMIM:618321 30576410;33224489;31755961 False 3 100;0;0 30.556 False ENSG00000213995 ENSG00000213995 HGNC:25576 NAXE gene NAXE Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, OMIM:617186 27616477;27290639;27122014 False 3 100;0;0 30.556 False ENSG00000163382 ENSG00000163382 HGNC:18453 NAXE gene NAXE Expert Review Green;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, OMIM:617186 27616477;27290639;27122014 False 3 100;0;0 30.556 False ENSG00000163382 ENSG00000163382 HGNC:18453 NAXE gene NAXE Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, OMIM:617186 27616477;27122014;27290639;30022751;31758406;31745726 False 3 100;0;0 30.556 False ENSG00000163382 ENSG00000163382 HGNC:18453 NBEA gene NBEA Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Global developmental delay;Intellectual disability;Seizures;No OMIM number 30269351;28554332;12746398;12826745;11450821;3377648;23277425;22109531;23153818 False 3 100;0;0 30.556 False ENSG00000172915 ENSG00000172915 HGNC:7648 NCDN gene NCDN Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual disability;epilepsy 33711248 False 3 100;0;0 30.556 False ENSG00000020129 ENSG00000020129 HGNC:17597 NCKAP1 gene NCKAP1 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual disability;Autism 33157009 False 3 100;0;0 30.556 False ENSG00000061676 ENSG00000061676 HGNC:7666 NDE1 gene NDE1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Lissencephaly 4 (with microcephaly), 614019;LISSENCEPHALY 4 (WITH MICROCEPHALY) False 3 100;0;0 30.556 False ENSG00000072864 ENSG00000072864 HGNC:17619 NDP gene NDP Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Norrie disease, 310600Exudative vitreoretinopathy, X-linked, 305390;NORRIE DISEASE False 3 100;0;0 30.556 False ENSG00000124479 ENSG00000124479 HGNC:7678 NDST1 gene NDST1 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mental retardation, autosomal recessive 46, 616116;MRT46;Intellectual disability 25125150;21937992 False 3 0;0;100 30.556 False Other - please provide details in the comments ENSG00000070614 ENSG00000070614 HGNC:7680 NDUFA1 gene NDUFA1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mitochondrial complex I deficiency, 252010;MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY (NUCLEAR GENES) False 3 100;0;0 30.556 False ENSG00000125356 ENSG00000125356 HGNC:7683 NDUFA1 gene NDUFA1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits);Isolated complex I deficiency 27604308;28247337;17262856;19185523;21596602 False 3 100;0;0 30.556 False ENSG00000125356 ENSG00000125356 HGNC:7683 NDUFA1 gene NDUFA1 Victorian Clinical Genetics Services;Expert Review Green;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Isolated complex I deficiency;Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases 27604308;28247337;17262856;19185523;21596602 False 3 100;0;0 30.556 True ENSG00000125356 ENSG00000125356 HGNC:7683 NDUFA10 gene NDUFA10 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Leigh syndrome, 256000;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex I Deficiency False 3 100;0;0 30.556 False ENSG00000130414 ENSG00000130414 HGNC:7684 NDUFA10 gene NDUFA10 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial Diseases;Isolated complex I deficiency;Leigh syndrome, 256000;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits);Mitochondrial Respiratory Chain Complex I Deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000130414 ENSG00000130414 HGNC:7684 NDUFA11 gene NDUFA11 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Isolated complex I deficiency;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits);Mitochondrial Respiratory Chain Complex I Deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000174886 ENSG00000174886 HGNC:20371 NDUFA11 gene NDUFA11 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex I Deficiency False 3 100;0;0 30.556 False ENSG00000174886 ENSG00000174886 HGNC:20371 NDUFA12 gene NDUFA12 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 23, OMIM:618244 21617257;33715266;35141356 False 3 100;0;0 30.556 False ENSG00000184752 ENSG00000184752 HGNC:23987 NDUFA12 gene NDUFA12 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 23, OMIM:618244 21617257;33715266;35141356 False 3 67;0;33 30.556 False ENSG00000184752 ENSG00000184752 HGNC:23987 NDUFA13 gene NDUFA13 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 28, OMIM:618249 25901006;32722639 False 3 75;0;25 30.556 False ENSG00000186010 ENSG00000186010 HGNC:17194 NDUFA13 gene NDUFA13 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 28, OMIM:618249 25901006;32722639 False 3 75;25;0 30.556 True ENSG00000186010 ENSG00000186010 HGNC:17194 NDUFA2 gene NDUFA2 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 13, MIM#618235 18513682;28857146 False 3 100;0;0 30.556 False ENSG00000131495 ENSG00000131495 HGNC:7685 NDUFA2 gene NDUFA2 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Leigh syndrome due to mitochondrial complex I deficiency, 256000;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex I Deficiency False 3 100;0;0 30.556 False ENSG00000131495 ENSG00000131495 HGNC:7685 NDUFA2 gene NDUFA2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leigh syndrome due to mitochondrial complex I deficiency, 256000;Mitochondrial Diseases;Isolated complex I deficiency;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits);Mitochondrial Respiratory Chain Complex I Deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000131495 ENSG00000131495 HGNC:7685 NDUFA4 gene NDUFA4 Expert Review Green;Expert Review Green;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Mitochondrial complex IV deficiency, nuclear type 21, OMIM:619065;mitochondrial complex IV deficiency, nuclear type 21, MONDO:0033656 23746447;29636225 False 3 50;50;0 30.556 False ENSG00000189043 ENSG00000189043 HGNC:7687 NDUFA4 gene NDUFA4 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Mitochondrial complex IV deficiency, nuclear type 21, OMIM:619065;mitochondrial complex IV deficiency, nuclear type 21, MONDO:0033656 23746447;29636225 False 3 50;50;0 30.556 False ENSG00000189043 ENSG00000189043 HGNC:7687 NDUFA6 gene NDUFA6 Expert Review Green;NHS GMS;Radboud University Medical Center, Nijmegen;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 33, OMIM:618253 30245030 False 3 0;100;0 30.556 False ENSG00000184983 ENSG00000184983 HGNC:7690 NDUFA6 gene NDUFA6 Expert Review Green;Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 33, OMIM:618253 30245030 False 3 0;100;0 30.556 False ENSG00000184983 ENSG00000184983 HGNC:7690 NDUFA8 gene NDUFA8 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 37, OMIM:619272 15576045;33153867;32385911 False 3 67;33;0 30.556 False ENSG00000119421 ENSG00000119421 HGNC:7692 NDUFA8 gene NDUFA8 Expert Review Green;NHS GMS;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 37, OMIM:619272 15576045;33153867;32385911 False 3 50;25;25 30.556 True ENSG00000119421 ENSG00000119421 HGNC:7692 NDUFA9 gene NDUFA9 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 26, 618247 28671271;22114105 False 3 50;50;0 30.556 False ENSG00000139180 ENSG00000139180 HGNC:7693 NDUFA9 gene NDUFA9 Expert Review Green;Expert Review Green;NHS GMS;London North GLH;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits);Leigh syndrome due to mitochondrial complex I deficiency, 256000 -3;Isolated complex I deficiency;Mitochondrial complex I deficiency, nuclear type 26, 618247;Leigh syndrome due to mitochondrial complex I deficiency, 256000 28671271;22114105 False 3 33;33;33 30.556 False ENSG00000139180 ENSG00000139180 HGNC:7693 NDUFAF1 gene NDUFAF1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial Leukoencephalopathy 21931170;16218961;17557076;25655951;24963768 False 3 0;0;0 30.556 False ENSG00000137806 ENSG00000137806 HGNC:18828 NDUFAF1 gene NDUFAF1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Isolated complex I deficiency;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors);Mitochondrial Respiratory Chain Complex I Deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000137806 ENSG00000137806 HGNC:18828 NDUFAF1 gene NDUFAF1 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex I Deficiency False 3 100;0;0 30.556 False ENSG00000137806 ENSG00000137806 HGNC:18828 NDUFAF2 gene NDUFAF2 Victorian Clinical Genetics Services;Expert Review Green;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Mitochondrial complex I deficiency, 252010;Leigh syndrome, 256000;Mitochondrial Respiratory Chain Complex I Deficiency False 3 100;0;0 30.556 True ENSG00000164182 ENSG00000164182 HGNC:28086 NDUFAF2 gene NDUFAF2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, 252010;Isolated complex I deficiency;Leigh syndrome, 256000;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors);Mitochondrial Respiratory Chain Complex I Deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000164182 ENSG00000164182 HGNC:28086 NDUFAF3 gene NDUFAF3 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency False 3 0;0;0 30.556 False ENSG00000178057 ENSG00000178057 HGNC:29918 NDUFAF3 gene NDUFAF3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Isolated complex I deficiency;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors);Mitochondrial Respiratory Chain Complex I Deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000178057 ENSG00000178057 HGNC:29918 NDUFAF3 gene NDUFAF3 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex I Deficiency False 3 100;0;0 30.556 False ENSG00000178057 ENSG00000178057 HGNC:29918 NDUFAF4 gene NDUFAF4 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex I Deficiency False 3 100;0;0 30.556 False ENSG00000123545 ENSG00000123545 HGNC:21034 NDUFAF4 gene NDUFAF4 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Isolated complex I deficiency;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors);Mitochondrial Respiratory Chain Complex I Deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000123545 ENSG00000123545 HGNC:21034 NDUFAF5 gene NDUFAF5 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex 1 deficiency, 252010;Mitochondrial Diseases;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors);Isolated complex I deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000101247 ENSG00000101247 HGNC:15899 NDUFAF5 gene NDUFAF5 Victorian Clinical Genetics Services;Expert Review Green;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Mitochondrial complex 1 deficiency, 252010;Mitochondrial Diseases PMID: 19542079;18940309 False 3 100;0;0 30.556 True ENSG00000101247 ENSG00000101247 HGNC:15899 NDUFAF6 gene NDUFAF6 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Leigh syndrome due to mitochondrial complex I deficiency, 256000 18614015;27623250;26741492 False 3 100;0;0 30.556 False ENSG00000156170 ENSG00000156170 HGNC:28625 NDUFAF6 gene NDUFAF6 London North GLH;NHS GMS;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leigh syndrome due to mitochondrial complex I deficiency, 256000;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors);Isolated complex I deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000156170 ENSG00000156170 HGNC:28625 NDUFAF8 gene NDUFAF8 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 34, OMIM:618776 27499296 False 3 0;0;0 30.556 False ENSG00000224877 ENSG00000224877 HGNC:33551 NDUFAF8 gene NDUFAF8 Expert Review Green;Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 34, OMIM:618776 27499296 False 3 0;0;0 30.556 False ENSG00000224877 ENSG00000224877 HGNC:33551 NDUFB10 gene NDUFB10 Expert Review Green;NHS GMS;Radboud University Medical Center, Nijmegen;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 35, OMIM:619003 28040730;32025618;33169436 False 3 60;40;0 30.556 False ENSG00000140990 ENSG00000140990 HGNC:7696 NDUFB10 gene NDUFB10 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 35, OMIM:619003 28040730;32025618;33169436 False 3 50;50;0 30.556 False ENSG00000140990 ENSG00000140990 HGNC:7696 NDUFB11 gene NDUFB11 Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Linear skin defects with multiple congenital anomalies 3;microphthalmia with linear skin defects syndrome;histiocytoid cardiomyopathy;Isolated complex I deficiency False 3 100;0;0 30.556 False ENSG00000147123 ENSG00000147123 HGNC:20372 NDUFB11 gene NDUFB11 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Isolated complex I deficiency;Linear skin defects with multiple congenital anomalies 3;histiocytoid cardiomyopathy;microphthalmia with linear skin defects syndrome False 3 100;0;0 30.556 True ENSG00000147123 ENSG00000147123 HGNC:20372 NDUFB3 gene NDUFB3 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 25, OMIM:618246 False 3 100;0;0 30.556 True ENSG00000119013 ENSG00000119013 HGNC:7698 NDUFB3 gene NDUFB3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 25, OMIM:618246 27604308 False 3 100;0;0 30.556 False ENSG00000119013 ENSG00000119013 HGNC:7698 NDUFB7 gene NDUFB7 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135 33502047;27626371;40025060 False 3 50;50;0 30.556 False ENSG00000099795 ENSG00000099795 HGNC:7702 NDUFB7 gene NDUFB7 Expert Review Green;NHS GMS;Radboud University Medical Center, Nijmegen;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135 33502047;27626371;40025060 False 3 50;50;0 30.556 False ENSG00000099795 ENSG00000099795 HGNC:7702 NDUFB8 gene NDUFB8 Expert Review Green;NHS GMS;Radboud University Medical Center, Nijmegen;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 32, 618252 27290639;29429571 False 3 0;100;0 30.556 False ENSG00000166136 ENSG00000166136 HGNC:7703 NDUFB8 gene NDUFB8 Expert Review Green;Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 32, 618252;No OMIM phenotype;Isolated complex I deficiency 27290639;29429571 False 3 0;100;0 30.556 False ENSG00000166136 ENSG00000166136 HGNC:7703 NDUFC2 gene NDUFC2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 36 OMIM:619170 32969598 False 3 50;50;0 30.556 False ENSG00000151366 ENSG00000151366 HGNC:7706 NDUFC2 gene NDUFC2 Expert Review Green;NHS GMS;Radboud University Medical Center, Nijmegen;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 36, OMIM:619170 32969598 False 3 67;33;0 30.556 False ENSG00000151366 ENSG00000151366 HGNC:7706 NDUFS1 gene NDUFS1 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226 False 3 100;0;0 30.556 False ENSG00000023228 ENSG00000023228 HGNC:7707 NDUFS1 gene NDUFS1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226 False 3 100;0;0 30.556 False ENSG00000023228 ENSG00000023228 HGNC:7707 NDUFS1 gene NDUFS1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226 Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits);Isolated complex I deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000023228 ENSG00000023228 HGNC:7707 NDUFS1 gene NDUFS1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226 25655951 False 3 0;0;0 30.556 False ENSG00000023228 ENSG00000023228 HGNC:7707 NDUFS2 gene NDUFS2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Isolated complex I deficiency;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits);Mitochondrial Respiratory Chain Complex I Deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000158864 ENSG00000158864 HGNC:7708 NDUFS2 gene NDUFS2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I disorders;Leigh syndrome associated with mitochondrial complex I deficiency;Mitochondrial Leukoencephalopathy;Leigh syndrome 20819849;11220739;25655951;22036843;23266820 False 3 0;0;0 30.556 False ENSG00000158864 ENSG00000158864 HGNC:7708 NDUFS2 gene NDUFS2 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex I Deficiency False 3 100;0;0 30.556 False ENSG00000158864 ENSG00000158864 HGNC:7708 NDUFS3 gene NDUFS3 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Leigh syndrome due to mitochondrial complex I deficiency, 256000Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex I Deficiency False 3 100;0;0 30.556 False ENSG00000213619 ENSG00000213619 HGNC:7710 NDUFS3 gene NDUFS3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial Diseases;Leigh syndrome due to mitochondrial complex I deficiency, 256000Mitochondrial complex I deficiency, 252010;Isolated complex I deficiency;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits);Mitochondrial Respiratory Chain Complex I Deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000213619 ENSG00000213619 HGNC:7710 NDUFS4 gene NDUFS4 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency;Mitochondrial complex I disorders;Mitochondrial Leukoencephalopathy;MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY 25655951 False 3 0;0;0 30.556 False ENSG00000164258 ENSG00000164258 HGNC:7711 NDUFS4 gene NDUFS4 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leigh syndrome, 256000Mitochondrial complex I deficiency, 252010;MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY (NUCLEAR GENES) False 3 100;0;0 30.556 False ENSG00000164258 ENSG00000164258 HGNC:7711 NDUFS4 gene NDUFS4 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leigh syndrome, 256000;Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Isolated complex I deficiency;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits);Mitochondrial Respiratory Chain Complex I Deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000164258 ENSG00000164258 HGNC:7711 NDUFS4 gene NDUFS4 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Leigh syndrome, 256000;Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex I Deficiency False 3 100;0;0 30.556 False ENSG00000164258 ENSG00000164258 HGNC:7711 NDUFS6 gene NDUFS6 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Complex I, mitochondrial respiratory chain, deficiency of, 252010;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex I Deficiency False 3 100;0;0 30.556 False ENSG00000145494 ENSG00000145494 HGNC:7713 NDUFS6 gene NDUFS6 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial Diseases;Isolated complex I deficiency;Complex I, mitochondrial respiratory chain, deficiency of, 252010;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits);Mitochondrial Respiratory Chain Complex I Deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000145494 ENSG00000145494 HGNC:7713 NDUFS7 gene NDUFS7 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial Diseases;Isolated complex I deficiency;Leigh syndrome, 256000;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits);Mitochondrial Respiratory Chain Complex I Deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000115286 ENSG00000115286 HGNC:7714 NDUFS7 gene NDUFS7 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Genetic leukoencephalopathies: mitochondrial disorders;General Leukodystrophy & Mitochondrial Leukoencephalopathy;Leigh syndrome;Mitochondrial Leukoencephalopathy;Mitochondrial respiratory chain complex I deficiency 25655951 False 3 0;0;0 30.556 False ENSG00000115286 ENSG00000115286 HGNC:7714 NDUFS7 gene NDUFS7 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leigh syndrome, 256000;MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY (NUCLEAR GENES) False 3 100;0;0 30.556 False ENSG00000115286 ENSG00000115286 HGNC:7714 NDUFS7 gene NDUFS7 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Leigh syndrome, 256000;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex I Deficiency False 3 100;0;0 30.556 False ENSG00000115286 ENSG00000115286 HGNC:7714 NDUFS8 gene NDUFS8 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Leigh syndrome due to mitochondrial complex I deficiency, 256000;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex I Deficiency False 3 100;0;0 30.556 False ENSG00000110717 ENSG00000110717 HGNC:7715 NDUFS8 gene NDUFS8 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leigh syndrome due to mitochondrial complex I deficiency, 256000;Mitochondrial Diseases;Isolated complex I deficiency;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits);Mitochondrial Respiratory Chain Complex I Deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000110717 ENSG00000110717 HGNC:7715 NDUFS8 gene NDUFS8 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leigh syndrome due to mitochondrial complex I deficiency, 256000;MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY (NUCLEAR GENES) False 3 100;0;0 30.556 False ENSG00000110717 ENSG00000110717 HGNC:7715 NDUFS8 gene NDUFS8 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I disorders;Leigh syndrome due to mitochondrial complex I deficiency;Mitochondrial Leukoencephalopathy 25655951 False 3 0;0;0 30.556 False ENSG00000110717 ENSG00000110717 HGNC:7715 NDUFV1 gene NDUFV1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, 252010;MITOCHONDRIAL COMPLEX I DEFICIENCY False 3 100;0;0 30.556 False ENSG00000167792 ENSG00000167792 HGNC:7716 NDUFV1 gene NDUFV1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Isolated complex I deficiency;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits);Mitochondrial Respiratory Chain Complex I Deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000167792 ENSG00000167792 HGNC:7716 NDUFV1 gene NDUFV1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial Leukoencephalopathy 26345448;26758110;27344648;25655951 False 3 0;0;0 30.556 False ENSG00000167792 ENSG00000167792 HGNC:7716 NDUFV1 gene NDUFV1 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex I Deficiency False 3 100;0;0 30.556 False ENSG00000167792 ENSG00000167792 HGNC:7716 NDUFV2 gene NDUFV2 Victorian Clinical Genetics Services;Expert Review Green;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 7, OMIM:618229 False 3 100;0;0 30.556 True ENSG00000178127 ENSG00000178127 HGNC:7717 NDUFV2 gene NDUFV2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 7, OMIM:618229;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits) 27604308 False 3 100;0;0 30.556 False ENSG00000178127 ENSG00000178127 HGNC:7717 NEDD4L gene NEDD4L Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Periventricular nodular heterotopia 7, 617201 23934111;27694961 False 3 40;0;60 30.556 False ENSG00000049759 ENSG00000049759 HGNC:7728 NEMF gene NEMF Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypotonia;Global developmental delay;Intellectual disability;Axonal neuropathy;Ataxia;Abnormal brain imaging;Kyphosis;Scoliosis;Tremor;Respiratory distress 27431290;32934225;33048237 False 3 100;0;0 30.556 False ENSG00000165525 ENSG00000165525 HGNC:10663 NEU1 gene NEU1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sialidosis, type I, OMIM:256550;Sialidosis, type II, OMIM:256550 False 3 100;0;0 30.556 False ENSG00000204386 ENSG00000204386 HGNC:7758 NEU1 gene NEU1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sialidosis, type I, OMIM:256550;Sialidosis, type II, OMIM:256550;Mucolipidosis, Type I 27604308 False 3 0;0;0 30.556 False ENSG00000204386 ENSG00000204386 HGNC:7758 NEUROD2 gene NEUROD2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental and epileptic encephalopathy 72, OMIM:618374 16504944;30323019;33438828 False 3 100;0;0 30.556 False ENSG00000171532 ENSG00000171532 HGNC:7763 NEUROG1 gene NEUROG1 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469 23419067;26077850;33439489;36647078 False 3 100;0;0 30.556 False ENSG00000181965 ENSG00000181965 HGNC:7764 NEXMIF gene NEXMIF Victorian Clinical Genetics Services;Expert Review Green;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Mental retardation, X-linked 98, 300912;KIAA2022 27358180;25529582 False 3 100;0;0 30.556 False ENSG00000050030 ENSG00000050030 HGNC:29433 NF1 gene NF1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurofibromatosis, type 1, 162200Leukemia, juvenile myelomonocytic, 607785Melanoma, desmoplastic neurotrophic (2)Neurofibromatosis, familial spinal, 162210Neurofibromatosis-Noonan syndrome, 601321Watson syndrome, 193520;NEUROFIBROMATOSIS-NOONAN SYNDROME (NFNS) 11704931;1745350;9529361;29588991;25529582;24896178 False 3 100;0;0 30.556 False ENSG00000196712 ENSG00000196712 HGNC:7765 NFASC gene NFASC Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with central and peripheral motor dysfunction, OMIM:618356;neurodevelopmental disorder with central and peripheral motor dysfunction, MONDO:003269 28940097;30124836;30850329;31501903 False 3 100;0;0 30.556 False ENSG00000163531 ENSG00000163531 HGNC:29866 NFIA gene NFIA Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Brain malformations with or without urinary tract defects, 613735;BRMUTD;Intellectual disability;Chromosome 1p32-p31 deletion syndrome, included 24462883;27081522;25714559;22031302;17530927 False 3 0;0;100 30.556 False ENSG00000162599 ENSG00000162599 HGNC:7784 NFIX gene NFIX Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted SOTOS-LIKE SYNDROME 20673863 False 3 100;0;0 30.556 False ENSG00000008441 ENSG00000008441 HGNC:7788 NFS1 gene NFS1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 52, OMIM:619386 24498631;33457206 False 3 60;0;40 30.556 False ENSG00000244005 ENSG00000244005 HGNC:15910 NFS1 gene NFS1 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Expert;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 52, OMIM:619386 16847322;24498631;33457206 False 3 100;0;0 30.556 False ENSG00000244005 ENSG00000244005 HGNC:15910 NFU1 gene NFU1 Victorian Clinical Genetics Services;Expert Review Green;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 1, OMIM:605711 False 3 100;0;0 30.556 True ENSG00000169599 ENSG00000169599 HGNC:16287 NFU1 gene NFU1 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 1, OMIM:605711 22077971;25918518;28470589;29441221;31516295;32747156;32669393 False 3 100;0;0 30.556 False ENSG00000169599 ENSG00000169599 HGNC:16287 NFU1 gene NFU1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 1, OMIM:605711 22077971;11156534 False 3 33;67;0 30.556 False ENSG00000169599 ENSG00000169599 HGNC:16287 NFU1 gene NFU1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 1, OMIM:605711;Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) 27604308 False 3 100;0;0 30.556 False ENSG00000169599 ENSG00000169599 HGNC:16287 NGLY1 gene NGLY1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal CONGENITAL DISORDER OF DEGLYCOSYLATION; CDDG 24651605 False 3 33;67;0 30.556 False ENSG00000151092 ENSG00000151092 HGNC:17646 NGLY1 gene NGLY1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal OrphaNet: ORPHA404454;Congenital disorder of deglycosylation 615273;Alacrimia-choreoathetosis-liver dysfunction syndrome;OMIM:615273 25220016;26350515;25900930;24651605;25605922;22581936;25707956 False 3 0;0;0 30.556 False ENSG00000151092 ENSG00000151092 HGNC:17646 NHLRC1 gene NHLRC1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epilepsy, progressive myoclonic 2B (Lafora) 27604308 False 3 0;0;0 30.556 False ENSG00000187566 ENSG00000187566 HGNC:21576 NHLRC2 gene NHLRC2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal FINCA syndrome, OMIM:618278 37188825;39328589 False 3 100;0;0 30.556 False ENSG00000196865 ENSG00000196865 HGNC:24731 NHS gene NHS Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Nance-Horan syndrome, 302350Cataract 40, X-linked, 302200;NANCE-HORAN SYNDROME (NHS) False 3 100;0;0 30.556 False ENSG00000188158 ENSG00000188158 HGNC:7820 NIPBL gene NIPBL Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Cornelia de Lange syndrome 1, 122470;CORNELIA DE LANGE SYNDROME TYPE 1 (CDLS1) False 3 100;0;0 30.556 False ENSG00000164190 ENSG00000164190 HGNC:28862 NKAP gene NKAP Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Global developmental delay;Intellectual disability;Intellectual developmental disorder, X-linked, syndromic, Hackman-Di Donato type #301039 26358559;26350204;31587868 False 3 25;0;75 30.556 False ENSG00000101882 ENSG00000101882 HGNC:29873 NKX2-1 gene NKX2-1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Goiter, familial, due to TTF-1 defect (1)Chorea, hereditary benign, 118700Choreoathetosis, hypothyroidism, and neonatal respiratory distress, 610978;BENIGN HEREDITARY CHOREA False 3 100;0;0 30.556 False ENSG00000136352 ENSG00000136352 HGNC:11825 NKX6-2 gene NKX6-2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy, OMIM:617560 False 3 0;0;0 30.556 False ENSG00000148826 ENSG00000148826 HGNC:19321 NLGN3 gene NLGN3 Victorian Clinical Genetics Services;Expert Review Green;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females AUTISM SPECTRUM DISORDERS False 3 100;0;0 30.556 False ENSG00000196338 ENSG00000196338 HGNC:14289 NNT gene NNT Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glucocorticoid deficiency 4, with or without mineralocorticoid deficiency, 614736 27129361;28546232 False 3 100;0;0 30.556 False ENSG00000112992 ENSG00000112992 HGNC:7863 NONO gene NONO Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Mental retardation, X-linked, syndromic 34, 300967;MENTAL RETARDATION, X-LINKED, SYNDROMIC, MIRCSOF-LANGOUET TYPE;MRXSML;Macrocephaly-intellectual disability-left ventricular non compaction syndrome;Syndromic intellectual disability 26571461;27329731;27550220 False 3 100;0;0 30.556 False ENSG00000147140 ENSG00000147140 HGNC:7871 NOTCH3 gene NOTCH3 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal neurodevelopmental disorder, MONDO:0700092;leukodystrophy, MONDO:0019046 39191170 False 3 100;0;0 30.556 False ENSG00000074181 ENSG00000074181 HGNC:7883 NOTCH3 gene NOTCH3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal neurodevelopmental disorder, MONDO:0700092 39191170 False 3 100;0;0 30.556 False ENSG00000074181 ENSG00000074181 HGNC:7883 NOVA2 gene NOVA2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities 618859 32197073 False 3 100;0;0 30.556 False ENSG00000104967 ENSG00000104967 HGNC:7887 NPC1 gene NPC1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal NIEMANN-PICK DISEASE, TYPE C1 10521297;9211849;12554680;11349231;11333381;10480349;11479732;9245994 False 3 33;67;0 30.556 False ENSG00000141458 ENSG00000141458 HGNC:7897 NPC1 gene NPC1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Niemann-Pick disease, type C1 27604308 False 3 0;0;0 30.556 False ENSG00000141458 ENSG00000141458 HGNC:7897 NPC2 gene NPC2 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal NIEMANN-PICK DISEASE, TYPE C2 17470133;12447927;11125141;11567215 False 3 33;67;0 30.556 False ENSG00000119655 ENSG00000119655 HGNC:14537 NPC2 gene NPC2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Niemann-Pick disease type C2, 607625 27604308 False 3 0;0;0 30.556 False ENSG00000119655 ENSG00000119655 HGNC:14537 NPHP1 gene NPHP1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Nephronophthisis 1, juvenile, 256100Senior-Loken syndrome-1, 266900Joubert syndrome 4, 609583;SENIOR-LOKEN SYNDROME TYPE 1 (SLSN1) False 3 100;0;0 30.556 False ENSG00000144061 ENSG00000144061 HGNC:7905 NR2F1 gene NR2F1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Bosch-Boonstra-Schaaf optic atrophy syndrome, OMIM:615722 24462372 False 3 33;67;0 30.556 False ENSG00000175745 ENSG00000175745 HGNC:7975 NR2F2 gene NR2F2 NHS GMS;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Congenital heart defects, multiple types, 4, 615779 29663647;37500725 False 3 80;0;20 30.556 False ENSG00000185551 ENSG00000185551 HGNC:7976 NR4A2 gene NR4A2 Expert Review Green;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism, OMIM:619911 29770430;30504930;28544326;27569545;23554088;28135719;27479843;25363768;32366965 False 3 100;0;0 30.556 False ENSG00000153234 ENSG00000153234 HGNC:7981 NRAS gene NRAS Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Autoimmune lymphoproliferative syndrome type IV, 614470Noonan syndrome 6, 613224Epidermal nevus, somatic, 162900Thyroid carcinoma, follicular, somatic, 188470Colorectal cancer, somatic, 114500;NOONAN SYNDROME TYPE 6 False 3 100;0;0 30.556 False ENSG00000213281 ENSG00000213281 HGNC:7989 NRCAM gene NRCAM Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with neuromuscular and skeletal abnormalities, OMIM:619833 35108495 False 3 100;0;0 30.556 False ENSG00000091129 ENSG00000091129 HGNC:7994 NRROS gene NRROS Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Seizures, early-onset, with neurodegeneration and brain calcification 618875 32100099;32197075;28459434 False 3 100;0;0 30.556 False ENSG00000174004 ENSG00000174004 HGNC:24613 NRXN1 gene NRXN1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Pitt-Hopkins-like syndrome 2, OMIM:614325 (AR);Complex neurodevelopmental disorder (AD) False 3 67;33;0 30.556 False ENSG00000179915 ENSG00000179915 HGNC:8008 NSD1 gene NSD1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Sotos syndrome 1, 117550Leukemia, acute myeloid, 601626 (1)Beckwith-Wiedemann syndrome, 130650;WEAVER SYNDROME (WES) False 3 100;0;0 30.556 False ENSG00000165671 ENSG00000165671 HGNC:14234 NSD2 gene NSD2 Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Rauch-Steindl syndrome, OMIM:619695;Rauch-Steindl syndrome, MONDO:0859219 29892088;29760529;29884796;30244530 False 3 100;0;0 30.556 False ENSG00000109685 ENSG00000109685 HGNC:12766 NSDHL gene NSDHL Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females CHILD syndrome, 308050CK syndrome, 300831;CONGENITAL HEMIDYSPLASIA WITH ICHTHYOSIFORM ERYTHRODERMA AND LIMB DEFECTS (CHILD) False 3 100;0;0 30.556 False ENSG00000147383 ENSG00000147383 HGNC:13398 NSDHL gene NSDHL London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Congenital hemidysplasia with ichtyosiform erythroderma and limb defects (Disorders of sterol biosynthesis);CHILD syndrome 308050 XLD;CK syndrome 300831 XLR 27604308 False 3 0;0;0 30.556 False ENSG00000147383 ENSG00000147383 HGNC:13398 NSRP1 gene NSRP1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal NSRP1-associated developmental delay, epilepsy and microcephaly 34385670 False 3 100;0;0 30.556 False ENSG00000126653 ENSG00000126653 HGNC:25305 NSUN2 gene NSUN2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mental Retardation, Recessive;Mental retardation, autosomal recessive 5, 611091;AUTOSOMAL- RECESSIVE INTELLECTUAL DISABILITY MRT5 False 3 100;0;0 30.556 False ENSG00000037474 ENSG00000037474 HGNC:25994 NSUN3 gene NSUN3 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 48, OMIM:619012 27356879;32488845 False 3 100;0;0 30.556 False ENSG00000178694 ENSG00000178694 HGNC:26208 NSUN3 gene NSUN3 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 48, OMIM:619012 27356879;32488845 False 3 50;50;0 30.556 False ENSG00000178694 ENSG00000178694 HGNC:26208 NT5C2 gene NT5C2 Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 45, autosomal recessive, 613162;Intellectual disability 20301682;24482476;19415352 False 3 100;0;0 30.556 False ENSG00000076685 ENSG00000076685 HGNC:8022 NT5C3A gene NT5C3A London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Anemia, hemolytic, due to UMPH1 deficiency, 266120;Uridine-5 -monophosphate hydrolase superactivity (Disorders of pyrimidine metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000122643 ENSG00000122643 HGNC:17820 NT5E gene NT5E Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Calcification of joints and arteries, OMIM:211800;hereditary arterial and articular multiple calcification syndrome, MONDO:0008895 21288095;26010187;28825389;32522903;34999808;26178434;27045881 False 3 100;0;0 30.556 False ENSG00000135318 ENSG00000135318 HGNC:8021 NTNG2 gene NTNG2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia, OMIM:618718 31372774;31668703 False 3 100;0;0 30.556 False ENSG00000196358 ENSG00000196358 HGNC:14288 NTRK1 gene NTRK1 Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Insensitivity to pain, congenital, with anhidrosis, 256800 8696348; 11071380;10090906;10330344 False 3 50;0;50 30.556 False ENSG00000198400 ENSG00000198400 HGNC:8031 NTRK2 gene NTRK2 Expert Review Green;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Epileptic encephalopathy, early infantile, 58, 617830;Obesity, hyperphagia, and developmental delay, 613886 29100083;28135719;15494731;27884935 False 3 100;0;0 30.556 False ENSG00000148053 ENSG00000148053 HGNC:8032 NUBPL gene NUBPL Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency;Mitochondrial Leukoencephalopathy False 3 0;0;0 30.556 False ENSG00000151413 ENSG00000151413 HGNC:20278 NUBPL gene NUBPL Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 21, OMIM:618242 0 False 3 33;67;0 30.556 False ENSG00000151413 ENSG00000151413 HGNC:20278 NUBPL gene NUBPL London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Isolated complex I deficiency;Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors);Mitochondrial Respiratory Chain Complex I Deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000151413 ENSG00000151413 HGNC:20278 NUBPL gene NUBPL Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency;Mitochondrial complex I deficiency, 252010;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex I Deficiency False 3 100;0;0 30.556 False ENSG00000151413 ENSG00000151413 HGNC:20278 NUDT2 gene NUDT2 Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular hypotonia;Global developmental delay;Intellectual disability;Polyneuropathy;no OMIM number 27431290;30059600;33058507 False 3 50;50;0 30.556 False ENSG00000164978 ENSG00000164978 HGNC:8049 NUP188 gene NUP188 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sandestig-Stefanova syndrome, 618804 32021605;32275884 False 3 100;0;0 30.556 False ENSG00000095319 ENSG00000095319 HGNC:17859 NUP214 gene NUP214 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal developmental delay;intellectual disability;epileptic encephalopathy;developmental regression;microcephaly;{Encephalopathy, acute, infection-induced, susceptibility to, 9}, 618426 31178128;30758658;29483668 False 3 67;33;0 30.556 False ENSG00000126883 ENSG00000126883 HGNC:8064 NUS1 gene NUS1 Expert Review Green;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Mental retardation, autosomal dominant 55, with seizures, OMIM:617831;Congenital disorder of glycosylation, type 1aa, OMIM:617082 25066056;29100083;24824130;30348779 False 3 100;0;0 30.556 False ENSG00000153989 ENSG00000153989 HGNC:21042 NUS1 gene NUS1 NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual developmental disorder, autosomal dominant 55, with seizures, OMIM:617831;?Congenital disorder of glycosylation, type 1aa, OMIM:617082 25066056;31656175;32334381;32485575;33731878 False 3 75;25;0 30.556 False ENSG00000153989 ENSG00000153989 HGNC:21042 OAT gene OAT London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ornithine aminotransferase deficiency (Disorders of ornithine or proline metabolism);Gyrate atrophy of choroid and retina with or without ornithinemia 27604308 False 3 0;0;0 30.556 False ENSG00000065154 ENSG00000065154 HGNC:8091 OCLN gene OCLN Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Severe developmental delay with microcephaly;Band-like calcification with simplified gyration and polymicrogyria;Band-like calcification with simplified gyration and polymicrogyria, 251290 24668585;26689621;23793442;20727516 False 3 0;0;0 30.556 False ENSG00000197822 ENSG00000197822 HGNC:8104 OCLN gene OCLN Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pseudo-TORCH syndrome 1, 251290 (includes profound developmental delay);Band-like calcification with simplified gyration and polymicrogyria 20727516 False 3 0;0;100 30.556 False ENSG00000197822 ENSG00000197822 HGNC:8104 OCRL gene OCRL Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Dent disease 2, OMIM:300555;Lowe syndrome, OMIM:309000 27604308;8504307;9632163;9632163;15627218;27625797;33517444 False 3 0;0;0 30.556 False ENSG00000122126 ENSG00000122126 HGNC:8108 OCRL gene OCRL Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Lowe syndrome, 309000Dent disease 2, 300555;LOWE OCULOCEREBRORENAL SYNDROME (OCRL) 25529582;24896178;15627218;33517444 False 3 100;0;0 30.556 False ENSG00000122126 ENSG00000122126 HGNC:8108 ODC1 gene ODC1 Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Bachmann-Bupp syndrome, OMIM:619075 30239107;30475435 False 3 100;0;0 30.556 False ENSG00000115758 ENSG00000115758 HGNC:8109 OFD1 gene OFD1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Oral-facial-digital syndrome 1, 311200Simpson-Golabi-Behmel syndrome, type 2, 300209Joubert syndrome 10, 300804;ORAL-FACIAL-DIGITAL SYNDROME TYPE 1 (OFD1) False 3 100;0;0 30.556 False ENSG00000046651 ENSG00000046651 HGNC:2567 OGDH gene OGDH Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Alpha-ketoglutarate dehydrogenase deficiency, OMIM:203740;oxoglutaricaciduria, MONDO:0008759 27604308;32383294;36520152 False 3 60;0;40 30.556 False ENSG00000105953 ENSG00000105953 HGNC:8124 OGDHL gene OGDHL Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Yoon-Bellen neurodevelopmental syndrome, OMIM:619701 28017472;34800363 False 3 100;0;0 30.556 False ENSG00000197444 ENSG00000197444 HGNC:25590 OGT gene OGT Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Mental retardation, X-linked 106, 300997 25679214;28302723;28584052 False 3 0;0;100 30.556 False ENSG00000147162 ENSG00000147162 HGNC:8127 OPA1 gene OPA1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Optic atrophy 1, OMIM:165500;Optic atrophy plus syndrome, OMIM:125250;Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type), OMIM:616896;Behr syndrome, OMIM:210000 27604308;28494813;27150940;24970096;11017079;11017080;17722006;25012220 False 3 100;0;0 30.556 False ENSG00000198836 ENSG00000198836 HGNC:8140 OPA1 gene OPA1 Victorian Clinical Genetics Services;Expert Review Green; Expert;Expert list;Radboud University Medical Center, Nijmegen;UKGTN Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Optic atrophy 1, OMIM:165500;Optic atrophy plus syndrome, OMIM:125250;Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type), OMIM:616896;Behr syndrome, OMIM:210000 28494813;27150940;24970096;11017079;11017080;17722006;25012220 False 3 100;0;0 30.556 True ENSG00000198836 ENSG00000198836 HGNC:8140 OPA1 gene OPA1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Optic atrophy plus syndrome, OMIM: 125250 39233737 False 3 100;0;0 30.556 False ENSG00000198836 ENSG00000198836 HGNC:8140 OPA3 gene OPA3 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal 3-methylglutaconic aciduria, type III, 258501Optic atrophy 3 with cataract, 165300 False 3 100;0;0 30.556 True ENSG00000125741 ENSG00000125741 HGNC:8142 OPA3 gene OPA3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Methylglutaconic aciduria type III, Costeff syndrome (Organic acidurias);3-methylglutaconic aciduria, type III, 258501Optic atrophy 3 with cataract, 165300 27604308 False 3 100;0;0 30.556 False ENSG00000125741 ENSG00000125741 HGNC:8142 OPA3 gene OPA3 Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-methylglutaconic aciduria, type III, 258501;Costeff syndrome; Cognitive regression 25201222; 11668429;24944951;25657044;20301646 False 3 50;50;0 30.556 False ENSG00000125741 ENSG00000125741 HGNC:8142 OPHN1 gene OPHN1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, 300486;MENTAL RETARDATION X-LINKED OPHN1-RELATED (MRXSO) False 3 100;0;0 30.556 False ENSG00000079482 ENSG00000079482 HGNC:8148 OSGEP gene OSGEP Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Galloway-Mowat syndrome 3, 617729;Intellectual disability 28805828 False 3 100;0;0 30.556 True ENSG00000092094 ENSG00000092094 HGNC:18028 OTC gene OTC London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Ornithine transcarbamylase deficiency, 311250;Ornithine transcarbamylase deficiency (Urea cycle disorders and inherited hyperammonaemias) 27604308 False 3 0;0;0 30.556 False ENSG00000036473 ENSG00000036473 HGNC:8512 OTC gene OTC Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females CGD Ornithine transcarbamylase deficiency, 311250;ORNITHINE TRANSCARBAMYLASE DEFICIENCY False 3 100;0;0 30.556 False ENSG00000036473 ENSG00000036473 HGNC:8512 OTUD5 gene OTUD5 Expert Review Green;Literature Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Multiple congenital anomalies-neurodevelopmental syndrome, X-linked, OMIM:301056 33131077;33523931 False 3 100;0;0 30.556 False ENSG00000068308 ENSG00000068308 HGNC:25402 OTUD6B gene OTUD6B Victorian Clinical Genetics Services;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, 617452 28343629 False 3 100;0;0 30.556 False ENSG00000155100 ENSG00000155100 HGNC:24281 OTUD7A gene OTUD7A Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal developmental and epileptic encephalopathy, MONDO:0100062;intellectual disability, MONDO:0001071 31997314;29395075;29395074;33381903;36180924 False 3 75;0;25 30.556 False ENSG00000169918 ENSG00000169918 HGNC:20718 OTX2 gene OTX2 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted MICROPHTHALMIA SYNDROMIC TYPE 5 (MCOPS5) 19956411;18628516;20396904;19965921;18854396;15846561 False 3 33;67;0 30.556 False ENSG00000165588 ENSG00000165588 HGNC:8522 OXCT1 gene OXCT1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Succinyl CoA:3-oxoacid CoA transferase deficiency, 245050 8751852;10964512;11757586;23420214;25778941 False 3 100;0;0 30.556 False ENSG00000083720 ENSG00000083720 HGNC:8527 OXCT1 gene OXCT1 NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Succinyl CoA:3-oxoacid CoA transferase deficiency;severe ketosis on fasting often ketotic in fed state no hepatomegaly;Succinyl-CoA:3-Oxoacid-CoA transferase (SCOT) deficiency (Disorders of ketone body metabolism);Succinyl CoA:3-oxoacid CoA transferase deficiency (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) 27604308 False 3 0;0;100 30.556 False ENSG00000083720 ENSG00000083720 HGNC:8527 OXR1 gene OXR1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cerebellar hypoplasia/atrophy, epilepsy, and global developmental delay 213000 31785787;22028674 False 3 100;0;0 30.556 False ENSG00000164830 ENSG00000164830 HGNC:15822 P4HTM gene P4HTM Expert Review;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Abnormality of the eye;Seizures;Dysautonomia;Central hypotonia;Muscular hypotonia;Hypoventilation;Intellectual disability;Sleep apnea;Global developmental delay;Central hypotonia, Muscular hypotonia, Global developmental delay, Intellectual disability, Seizures, Abnormality of the eye, Hypoventilation, Sleep apnea, Dysautonomia 30940925;25078763 False 3 100;0;0 30.556 False ENSG00000178467 ENSG00000178467 HGNC:28858 PABPC1 gene PABPC1 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Global developmental delay;Expressive language delay;Intellectual disability;Behavioral abnormality;Seizures 35511136 False 3 50;25;25 30.556 False ENSG00000070756 ENSG00000070756 HGNC:8554 PACS1 gene PACS1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Mental retardation, autosomal dominant 17, 615009;INTELLECTUAL DISABILITY False 3 100;0;0 30.556 False ENSG00000175115 ENSG00000175115 HGNC:30032 PACS2 gene PACS2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Epileptic encephalopathy, early infantile, 66, 618067;Global developmental delay;Intellectual disability;Seizures;Abnormality of the cerebellum 29656858;22488736;28867141 False 3 100;0;0 30.556 True ENSG00000179364 ENSG00000179364 HGNC:23794 PAFAH1B1 gene PAFAH1B1 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Lissencephaly 1, OMIM:607432;Subcortical laminar heterotopia, OMIM:607432 False 3 0;0;0 30.556 False ENSG00000007168 ENSG00000007168 HGNC:8574 PAFAH1B1 gene PAFAH1B1 Victorian Clinical Genetics Services;Expert Review Green;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Lissencephaly 1, OMIM:607432;Subcortical laminar heterotopia, OMIM:607432 False 3 100;0;0 30.556 False ENSG00000007168 ENSG00000007168 HGNC:8574 PAH gene PAH London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Phenylketonuria 27604308;24816252 False 3 0;0;0 30.556 False ENSG00000171759 ENSG00000171759 HGNC:8582 PAH gene PAH Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Phenylketonuria, 261600[Hyperphenylalaninemia, non-PKU mild], 261600;NON-PHENYLKETONURIA HYPERPHENYLALANINEMIA (NON-PKU HPA) False 3 100;0;0 30.556 False ENSG00000171759 ENSG00000171759 HGNC:8582 PAK1 gene PAK1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual developmental disorder with macrocephaly, seizures, and speech delay, 618158 30290153;31504246 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000149269 ENSG00000149269 HGNC:8590 PAK3 gene PAK3 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked 30/47, 300558;Mental Retardation, X-linked;AGENESIS OF THE CORPUS CALLOSUM False 3 100;0;0 30.556 False ENSG00000077264 ENSG00000077264 HGNC:8592 PAN2 gene PAN2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental delay with variable cardiac and renal congenital anomalies and dysmorphic facies, OMIM:621384 29620724;35304602 False 3 67;33;0 30.556 False ENSG00000135473 ENSG00000135473 HGNC:20074 PANK2 gene PANK2 Expert Review Green;NHS GMS;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal HARP syndrome, OMIM:607236;Neurodegeneration with brain iron accumulation 1, OMIM:234200 11479594;12510040;25778941;28863176 False 3 100;0;0 30.556 False ENSG00000125779 ENSG00000125779 HGNC:15894 PANK2 gene PANK2 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal HARP syndrome 607236;Neurodegeneration with brain iron accumulation 234200 27604308;11479594;12510040;12058097;14638969;16240131 False 3 100;0;0 30.556 False ENSG00000125779 ENSG00000125779 HGNC:15894 PARN gene PARN Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dyskeratosis congenita, autosomal recessive 6, OMIM:616353 25529582;25893599;26342108 False 3 100;0;0 30.556 False ENSG00000140694 ENSG00000140694 HGNC:8609 PARS2 gene PARS2 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Epileptic encephalopathy, early infantile, 75, 618437Alpers syndrome.;Epileptic encephalopathy, early infantile, 75, 618437;Alpers syndrome 28077841;25629079;29410512;29915213 False 3 100;0;0 30.556 False ENSG00000162396 ENSG00000162396 HGNC:30563 PARS2 gene PARS2 Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Alpers syndrome;Epileptic encephalopathy, early infantile, 75, 618437 25629079;29915213;29410512;28077841 False 3 100;0;0 30.556 False ENSG00000162396 ENSG00000162396 HGNC:30563 PAX8 gene PAX8 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia, 218700;CONGENITAL HYPOTHYROIDISM NON-GOITROUS TYPE 2 (CHNG2) False 3 100;0;0 30.556 False ENSG00000125618 ENSG00000125618 HGNC:8622 PBX1 gene PBX1 Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay 28566479;29036646;28270404 False 3 100;0;0 30.556 False ENSG00000185630 ENSG00000185630 HGNC:8632 PC gene PC Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pyruvate carboxylase deficiency, OMIM:266150 False 3 100;0;0 30.556 False ENSG00000173599 ENSG00000173599 HGNC:8636 PC gene PC London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pyruvate carboxylase deficiency, OMIM:266150 27604308 False 3 100;0;0 30.556 False ENSG00000173599 ENSG00000173599 HGNC:8636 PC gene PC Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pyruvate carboxylase deficiency, OMIM:266150 False 3 100;0;0 30.556 True ENSG00000173599 ENSG00000173599 HGNC:8636 PCBD1 gene PCBD1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperphenylalaninemia, BH4-deficient, D 27604308 False 3 0;0;0 30.556 False ENSG00000166228 ENSG00000166228 HGNC:8646 PCCA gene PCCA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Propionicacidemia;Propionic acidemia;Propionicacidemia 606054;metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections;Propionic aciduria (Organic acidurias) 27604308 False 3 0;0;0 30.556 False ENSG00000175198 ENSG00000175198 HGNC:8653 PCCA gene PCCA Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal PROPIONIC ACIDEMIA 10820128;8295402;8411997;17966092;9887338;12189489;9683601;9385377;10101253;8225321 False 3 33;67;0 30.556 False ENSG00000175198 ENSG00000175198 HGNC:8653 PCCB gene PCCB Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal PROPIONIC ACIDEMIA 0 False 3 33;67;0 30.556 False ENSG00000114054 ENSG00000114054 HGNC:8654 PCCB gene PCCB London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal as PCCA (metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections);Propionic acidemia;Propionicacidemia 606054;Propionicacidemia;Propionic aciduria (Organic acidurias) 27604308 False 3 0;0;0 30.556 False ENSG00000114054 ENSG00000114054 HGNC:8654 PCDH12 gene PCDH12 Expert Review Green;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal intellectual disability;microcephaly;epilepsy;perithalamic hyperechogenicity;periventricular hyperechogenicity;midbrain abnormalities;hypothalamic abnormalities;Microcephaly, seizures, spasticity, and brain calcification, 251280 27164683;28804758;29556033;30178464;30459466;18477666 False 3 0;0;100 30.556 False ENSG00000113555 ENSG00000113555 HGNC:8657 PCDH19 gene PCDH19 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Epileptic encephalopathy, early infantile, 9, 300088;EPILEPTIC ENCEPHALOPATHY EARLY INFANTILE TYPE 9 (EIEE9) 18469813;5116697;19752159;19214208;25529582;24896178, 28669061;28462982 False 3 100;0;0 30.556 False ENSG00000165194 ENSG00000165194 HGNC:14270 PCDHGC4 gene PCDHGC4 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with poor growth and skeletal anomalies, OMIM:619880 34244665 False 3 100;0;0 30.556 False ENSG00000242419 ENSG00000242419 HGNC:8717 PCGF2 gene PCGF2 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual disability;dysmorphic features;Global developmental delay;Abnormality of the cardiovascular system;Abnormality of the cerebrum;Abnormality of the skeletal system 25529582;25533962;30343942 False 3 80;0;20 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000056661 ENSG00000277258 HGNC:12929 PCK1 gene PCK1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Phosphoenolpyruvate carboxykinase deficiency, cytosolic 261680 27604308;24863970;26971250;28216384 False 3 0;0;0 30.556 False ENSG00000124253 ENSG00000124253 HGNC:8724 PCNT gene PCNT Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720 False 3 100;0;0 30.556 False ENSG00000160299 ENSG00000160299 HGNC:16068 PCSK9 gene PCSK9 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Hypercholesterolemia, familial, 3 603776;{Low density lipoprotein cholesterol level QTL 1} 603776 27604308;12730697;14727179;15772090;15654334;16909389;26541928 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000169174 ENSG00000169174 HGNC:20001 PCYT2 gene PCYT2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 82, autosomal recessive, 618770;Global developmental delay;Developmental regression;Intellectual disability;Spastic paraparesis;Seizures;Spastic tetraparesis;Cerebral atrophy;Cerebellar atrophy 31637422 False 3 100;0;0 30.556 False ENSG00000185813 ENSG00000185813 HGNC:8756 PDE12 gene PDE12 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal mitochondrial disease, MONDO:0044970 28745585;29903433;39567835 False 3 67;0;33 30.556 False ENSG00000174840 ENSG00000174840 HGNC:25386 PDE12 gene PDE12 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal mitochondrial disease, MONDO:0044970 28745585;29903433;39567835 False 3 75;0;25 30.556 False ENSG00000174840 ENSG00000174840 HGNC:25386 PDE4D gene PDE4D Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Acrodysostosis 2, with or without hormone resistance, 614613;Acrodysostosis Orphanet:950 False 3 100;0;0 30.556 False Other - please provide details in the comments ENSG00000113448 ENSG00000113448 HGNC:8783 PDGFB gene PDGFB Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Fahr syndrome;Basal ganglia calcification, idiopathic, 5, 615483 26129893;25211641;27227165 - c.3G>C variant identified in 5 affected members of a family False 3 0;0;0 30.556 False ENSG00000100311 ENSG00000100311 HGNC:8800 PDGFRB gene PDGFRB Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Fahr syndrome;Calcifications in basal ganglia;Basal ganglia calcification idiopathic 4, 615007 23255827 - original family report and sproadic case report;24796542 - an additional case report of a idiopathic basal ganglia calcification patient with the p.R695C mutation, which resulted in partial loss of autophosphorylation;25292412 - functional studies;26599395 - mouse models and functional studies;26129893;34494111 False 3 100;0;0 30.556 False ENSG00000113721 ENSG00000113721 HGNC:8804 PDGFRB gene PDGFRB Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Kosaki overgrowth syndrome, 616592;Intellectual disability 23731537;25454926;25454926;29226947;28639748 False 3 60;40;0 30.556 False ENSG00000113721 ENSG00000113721 HGNC:8804 PDHA1 gene PDHA1 Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Pyruvate dehydrogenase E1-alpha deficiency, 312170Leigh syndrome, X-linked, 308930;PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY IN FEMALES False 3 100;0;0 30.556 False ENSG00000131828 ENSG00000131828 HGNC:8806 PDHA1 gene PDHA1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Pyruvate dehydrogenase E1? subunit deficiency (Disorders of pyruvate metabolism);Leigh syndrome, X-linked, 308930;Pyruvate dehydrogenase E1-alpha deficiency, 312170 27604308 False 3 100;0;0 30.556 False ENSG00000131828 ENSG00000131828 HGNC:8806 PDHA1 gene PDHA1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Pyruvate dehydrogenase E1-alpha deficiency, 312170;Leigh syndrome, X-linked, 308930 False 3 100;0;0 30.556 True ENSG00000131828 ENSG00000131828 HGNC:8806 PDHB gene PDHB Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pyruvate dehydrogenase E1-beta deficiency, OMIM:614111 15138885;26014431;18164639;19924563 False 3 100;0;0 30.556 False ENSG00000168291 ENSG00000168291 HGNC:8808 PDHB gene PDHB Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pyruvate dehydrogenase E1-beta deficiency, OMIM:614111 False 3 100;0;0 30.556 True ENSG00000168291 ENSG00000168291 HGNC:8808 PDHB gene PDHB London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pyruvate dehydrogenase E1-beta deficiency, OMIM:614111 27604308 False 3 100;0;0 30.556 False ENSG00000168291 ENSG00000168291 HGNC:8808 PDHX gene PDHX London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Lacticacidemia due to PDX1 deficiency, OMIM:245349 27604308 False 3 100;0;0 30.556 False ENSG00000110435 ENSG00000110435 HGNC:21350 PDHX gene PDHX Expert Review Green;Victorian Clinical Genetics Services;Literature;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Lacticacidemia due to PDX1 deficiency, OMIM:245349 False 3 100;0;0 30.556 False ENSG00000110435 ENSG00000110435 HGNC:21350 PDHX gene PDHX Victorian Clinical Genetics Services;Expert Review Green;Expert Review;Other Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Lacticacidemia due to PDX1 deficiency, OMIM:245349 False 3 100;0;0 30.556 True ENSG00000110435 ENSG00000110435 HGNC:21350 PDK3 gene PDK3 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) ?Charcot-Marie-Tooth disease, X-linked dominant, 6 300905 23297365;26801680;27388934;28902413;32504000;34387338 False 3 50;25;25 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000067992 ENSG00000067992 HGNC:8811 PDP1 gene PDP1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pyruvate dehydrogenase phosphatase deficiency, 608782;Pyruvate dehydrogenase phosphatase deficiency (Disorders of pyruvate metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000164951 ENSG00000164951 HGNC:9279 PDP1 gene PDP1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pyruvate dehydrogenase phosphatase deficiency, 608782 False 3 100;0;0 30.556 True ENSG00000164951 ENSG00000164951 HGNC:9279 PDSS1 gene PDSS1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of ubiquinone metabolism and biosynthesis;Coenzyme Q10 deficiency, primary, 2, 614651 PMID: 17332895 (2007) - Report a homozygous nucleotide substitution modifying a conserved amino acid of the protein (D308E) in a consanguineous family with CoQ10 deficiency;PMID: 22494076 (2012) - A girl with developmental delay, nephrotic syndrome, and failure to thrive was reported to be a compound heterozygote for two novel variants in PDSS1 (p.Arg221Term and p.Ser370Arg). False 3 100;0;0 30.556 False ENSG00000148459 ENSG00000148459 HGNC:17759 PDSS1 gene PDSS1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Coenzyme Q10 deficiency, primary, 2, 614651;COENZYME Q10 DEFICIENCY, PRIMARY, 2 False 3 100;0;0 30.556 False ENSG00000148459 ENSG00000148459 HGNC:17759 PDSS1 gene PDSS1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Coenzyme Q10 deficiency, primary, 2, 614651;Disorders of CoQ10 biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Disorders of ubiquinone metabolism and biosynthesis 27604308 False 3 100;0;0 30.556 False ENSG00000148459 ENSG00000148459 HGNC:17759 PDSS2 gene PDSS2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Coenzyme Q10 deficiency, primary, 3, 614652;Disorders of CoQ10 biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Disorders of ubiquinone metabolism and biosynthesis 27604308 False 3 100;0;0 30.556 False ENSG00000164494 ENSG00000164494 HGNC:23041 PDSS2 gene PDSS2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of ubiquinone metabolism and biosynthesis;Coenzyme Q10 deficiency, primary, 3, 614652 False 3 100;0;0 30.556 True ENSG00000164494 ENSG00000164494 HGNC:23041 PDSS2 gene PDSS2 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Coenzyme Q10 deficiency, primary, 3, 614652;COENZYME Q10 DEFICIENCY, PRIMARY, 3 False 3 100;0;0 30.556 False ENSG00000164494 ENSG00000164494 HGNC:23041 PDZD8 gene PDZD8 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Global developmental delay;Intellectual disability;Autistic behavior;Behavioral abnormality;Myopathy;Abnormality of the face;Hypertelorism;Seizures;Disproportionate tall stature 35227461 False 3 67;33;0 30.556 False ENSG00000165650 ENSG00000165650 HGNC:26974 PEPD gene PEPD Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Prolidase deficiency, 170100;PROLIDASE DEFICIENCY (PD) 1972707;6637477;2365824;16470701;8900231;15309682;17142620;19308961 False 3 100;0;0 30.556 False ENSG00000124299 ENSG00000124299 HGNC:8840 PEPD gene PEPD Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Prolidase deficiency 170100 27604308;2365824;2365824;8198124;15309682;16470701 False 3 0;0;0 30.556 False ENSG00000124299 ENSG00000124299 HGNC:8840 PET100 gene PET100 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;Complex IV-deficient Leigh syndrome;Mitochondrial complex IV deficiency, nuclear type 12 OMIM:619055 26425749;24462369;25293719;31406627 False 3 50;50;0 30.556 False ENSG00000229833 ENSG00000229833 HGNC:40038 PET100 gene PET100 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leigh syndrome;Mitochondrial complex IV deficiency, 220110;Isolated complex IV deficiency 24462369 False 3 100;0;0 30.556 False ENSG00000229833 ENSG00000229833 HGNC:40038 PET100 gene PET100 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex IV deficiency;Mitochondrial complex IV deficiency, 220110;Leigh syndrome PMID: 24462369 False 3 100;0;0 30.556 True ENSG00000229833 ENSG00000229833 HGNC:40038 PEX1 gene PEX1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of peroxisome biogenesis;Peroxisome biogenesis disorder 1B (NALD/IRD) 601539;Peroxisome biogenesis disorder 1A (Zellweger) 214100 27604308 False 3 0;0;0 30.556 False ENSG00000127980 ENSG00000127980 HGNC:8850 PEX1 gene PEX1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome-Associated Disorders & Zellweger Syndrome;Peroxisome biogenesis disorder 1A,B;General Leukodystrophy & Mitochondrial Leukoencephalopathy;Peroxisome biogenesis disorder 1A (Zellweger) 25655951 False 3 0;0;0 30.556 False ENSG00000127980 ENSG00000127980 HGNC:8850 PEX1 gene PEX1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome biogenesis disorder 1A (Zellweger), 214100Peroxisome biogenesis disorder 1B (NALD/IRD), 601539;PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 1 (PBD-CG1) False 3 100;0;0 30.556 False ENSG00000127980 ENSG00000127980 HGNC:8850 PEX10 gene PEX10 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome-Associated Disorders & Zellweger Syndrome;ZELLWEGER SYNDROME;PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 7 25655951 False 3 0;0;0 30.556 False ENSG00000157911 ENSG00000157911 HGNC:8851 PEX10 gene PEX10 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of peroxisome biogenesis;Peroxisome biogenesis disorder 6A (Zellweger) 614870;Peroxisome biogenesis disorder 6B 614871 27604308 False 3 0;0;0 30.556 False ENSG00000157911 ENSG00000157911 HGNC:8851 PEX10 gene PEX10 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome biogenesis disorder 6A (Zellweger), 614870Peroxisome biogenesis disorder 6B, 614871;ADRENOLEUKODYSTROPHY NEONATAL (NALD) False 3 100;0;0 30.556 False ENSG00000157911 ENSG00000157911 HGNC:8851 PEX11B gene PEX11B Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome biogenesis disorder 14B, 614920;Intellectual disability 22581968;28129423 False 3 33;0;67 30.556 False ENSG00000131779 ENSG00000131779 HGNC:8853 PEX11B gene PEX11B Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome biogenesis disorder 14B False 3 0;0;0 30.556 False ENSG00000131779 ENSG00000131779 HGNC:8853 PEX12 gene PEX12 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome-Associated Disorders & Zellweger Syndrome;Peroxisome biogenesis disorder 3A (Zellweger);General Leukodystrophy & Mitochondrial Leukoencephalopathy;Peroxisome biogenesis disorder 3B;Peroxisome biogenesis disorder 3A,B 25655951 False 3 0;0;0 30.556 False ENSG00000108733 ENSG00000108733 HGNC:8854 PEX12 gene PEX12 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome biogenesis disorder 3A (Zellweger), 614859Peroxisome biogenesis disorder 3B, 266510;ZELLWEGER SYNDROME (ZWS) False 3 100;0;0 30.556 False ENSG00000108733 ENSG00000108733 HGNC:8854 PEX12 gene PEX12 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of peroxisome biogenesis;Peroxisome biogenesis disorder 3A (Zellweger), 614859;Peroxisome biogenesis disorder 3B 27604308 False 3 0;0;0 30.556 False ENSG00000108733 ENSG00000108733 HGNC:8854 PEX13 gene PEX13 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of peroxisome biogenesis;Peroxisome biogenesis disorder 11A (Zellweger) 27604308 False 3 0;0;0 30.556 False ENSG00000162928 ENSG00000162928 HGNC:8855 PEX13 gene PEX13 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome biogenesis disorder 11A (Zellweger), 614883Peroxisome biogenesis disorder 11B, 614885;ADRENOLEUKODYSTROPHY NEONATAL (NALD) False 3 100;0;0 30.556 False ENSG00000162928 ENSG00000162928 HGNC:8855 PEX13 gene PEX13 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome-Associated Disorders & Zellweger Syndrome;Peroxisome biogenesis disorder 11A (Zellweger);Peroxisome biogenesis disorder 11B 25655951 False 3 0;0;0 30.556 False ENSG00000162928 ENSG00000162928 HGNC:8855 PEX14 gene PEX14 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome biogenesis disorder 13A (Zellweger), OMIM:614887;peroxisome biogenesis disorder 13A (Zellweger), MONDO:0013952 27604308;37493040 False 3 100;0;0 30.556 False ENSG00000142655 ENSG00000142655 HGNC:8856 PEX14 gene PEX14 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ZELLWEGER SYNDROME (ZWS) 0 False 3 33;67;0 30.556 False ENSG00000142655 ENSG00000142655 HGNC:8856 PEX16 gene PEX16 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of peroxisome biogenesis;Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum;Peroxisome biogenesis disorder 8A, (Zellweger), 614876;Peroxisomal biogenesis disorders;Zellweger Syndrome 27604308 False 3 0;0;0 30.556 False ENSG00000121680 ENSG00000121680 HGNC:8857 PEX16 gene PEX16 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome-Associated Disorders & Zellweger Syndrome;Peroxisome biogenesis disorder 8A, (Zellweger);Peroxisome biogenesis disorder 8B;PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 9 False 3 0;0;0 30.556 False ENSG00000121680 ENSG00000121680 HGNC:8857 PEX16 gene PEX16 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome biogenesis disorder 8A, (Zellweger), 614876Peroxisome biogenesis disorder 8B, 614877;PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 9 (PBD-CG9) False 3 100;0;0 30.556 False ENSG00000121680 ENSG00000121680 HGNC:8857 PEX19 gene PEX19 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome biogenesis disorder 12A (Zellweger), 614886;ZELLWEGER SYNDROME (ZWS) False 3 100;0;0 30.556 False ENSG00000162735 ENSG00000162735 HGNC:9713 PEX19 gene PEX19 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of peroxisome biogenesis;Peroxisome biogenesis disorder 12A (Zellweger) 27604308 False 3 0;0;0 30.556 False ENSG00000162735 ENSG00000162735 HGNC:9713 PEX2 gene PEX2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome biogenesis disorder 5A (Zellweger) 25655951 False 3 0;0;0 30.556 False ENSG00000164751 ENSG00000164751 HGNC:9717 PEX2 gene PEX2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of peroxisome biogenesis;Peroxisome biogenesis disorder 5A (Zellweger), 614866;Peroxisome biogenesis disorder 5B, 614867 27604308 False 3 0;0;0 30.556 False ENSG00000164751 ENSG00000164751 HGNC:9717 PEX2 gene PEX2 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome biogenesis disorder 5A (Zellweger), 614866Peroxisome biogenesis disorder 5B, 614867;ZELLWEGER SYNDROME (ZWS) False 3 100;0;0 30.556 False ENSG00000164751 ENSG00000164751 HGNC:9717 PEX26 gene PEX26 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of peroxisome biogenesis;Peroxisome biogenesis disorder 7A (Zellweger) 61487;Peroxisome biogenesis disorder 7B 614873 27604308 False 3 0;0;0 30.556 False ENSG00000215193 ENSG00000215193 HGNC:22965 PEX26 gene PEX26 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome biogenesis disorder 7A (Zellweger), 614872Peroxisome biogenesis disorder 7B, 614873;INFANTILE REFSUM DISEASE (IRD) False 3 100;0;0 30.556 False ENSG00000215193 ENSG00000215193 HGNC:22965 PEX26 gene PEX26 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome-Associated Disorders & Zellweger Syndrome 25655951 False 3 0;0;0 30.556 False ENSG00000215193 ENSG00000215193 HGNC:22965 PEX3 gene PEX3 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome biogenesis disorder 10A (Zellweger) 614882 23245813;10968777;25655951 False 3 0;0;0 30.556 False ENSG00000034693 ENSG00000034693 HGNC:8858 PEX3 gene PEX3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of peroxisome biogenesis;Peroxisome biogenesis disorder 10A (Zellweger) 614882 27604308 False 3 0;0;0 30.556 False ENSG00000034693 ENSG00000034693 HGNC:8858 PEX3 gene PEX3 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome biogenesis disorder 10A (Zellweger), 614882;PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 12 (PBD-CG12) False 3 100;0;0 30.556 False ENSG00000034693 ENSG00000034693 HGNC:8858 PEX5 gene PEX5 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome biogenesis disorder 2A (Zellweger), 214110Peroxisome biogenesis disorder 2B, 202370;ADRENOLEUKODYSTROPHY NEONATAL (NALD) False 3 100;0;0 30.556 False ENSG00000139197 ENSG00000139197 HGNC:9719 PEX5 gene PEX5 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of peroxisome biogenesis;Peroxisome biogenesis disorder 2A (Zellweger) 27604308 False 3 0;0;0 30.556 True ENSG00000139197 ENSG00000139197 HGNC:9719 PEX5 gene PEX5 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome biogenesis disorder 2A (Zellweger) 27290639;26220973 False 3 0;0;0 30.556 False ENSG00000139197 ENSG00000139197 HGNC:9719 PEX6 gene PEX6 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Peroxisome biogenesis disorder 4A (Zellweger) OMIM:614862;peroxisome biogenesis disorder 4A (Zellweger) MONDO:0013930;Peroxisome biogenesis disorder 4B OMIM:614863;peroxisome biogenesis disorder 4B MONDO:0013931 27604308;29220678;20301621 False 3 100;0;0 30.556 False Other ENSG00000124587 ENSG00000124587 HGNC:8859 PEX6 gene PEX6 NHS GMS;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862;Peroxisome biogenesis disorder 4B, OMIM:614863 25529582;29220678 False 3 100;0;0 30.556 False ENSG00000124587 ENSG00000124587 HGNC:8859 PEX6 gene PEX6 NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862;Peroxisome biogenesis disorder 4B, OMIM:614863 25655951;29220678 False 3 0;0;0 30.556 False ENSG00000124587 ENSG00000124587 HGNC:8859 PEX7 gene PEX7 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Rhizomelic chondrodysplasia punctata, type 1, 215100;Peroxisome biogenesis disorder 9B, 614879;REFSUM DISEASE (RD) False 3 100;0;0 30.556 False ENSG00000112357 ENSG00000112357 HGNC:8860 PEX7 gene PEX7 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peroxisome biogenesis disorder 9B 614879;Rhizomelic chondrodysplasia punctata, type 1;Rhizomelic chondrodysplasia punctata type 1 (Peroxisomal disorders) 27604308 False 3 0;0;0 30.556 False ENSG00000112357 ENSG00000112357 HGNC:8860 PFKM gene PFKM London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycogen storage disease VII 27604308 False 3 100;0;0 30.556 False ENSG00000152556 ENSG00000152556 HGNC:8877 PGAM2 gene PGAM2 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycogen storage disease X 261670 27604308;28779239 False 3 100;0;0 30.556 False ENSG00000164708 ENSG00000164708 HGNC:8889 PGAP1 gene PGAP1 Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mental retardation, autosomal recessive 42, 615802 27206732;26350515; 25804403;24784135;24482476; 25823418;26050939 False 3 100;0;0 30.556 False ENSG00000197121 ENSG00000197121 HGNC:25712 PGAP2 gene PGAP2 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperphosphatasia with mental retardation syndrome 3, 614207;INTELLECTUAL DISABILITY False 3 100;0;0 30.556 False ENSG00000148985 ENSG00000148985 HGNC:17893 PGAP2 gene PGAP2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperphosphatasia with mental retardation syndrome 3 614207;PGAP2-CDG (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation) 27604308 False 3 0;0;0 30.556 False ENSG00000148985 ENSG00000148985 HGNC:17893 PGAP3 gene PGAP3 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 4 24439110 False 3 100;0;0 30.556 False ENSG00000161395 ENSG00000161395 HGNC:23719 PGAP3 gene PGAP3 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperphosphatasia with mental retardation syndrome 4 24439110 False 3 0;0;0 30.556 False ENSG00000161395 ENSG00000161395 HGNC:23719 PGK1 gene PGK1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Phosphoglycerate kinase 1 deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000102144 ENSG00000102144 HGNC:8896 PGK1 gene PGK1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Phosphoglycerate kinase 1 deficiency, 300653;PHOSPHOGLYCERATE KINASE 1 DEFICIENCY (PGK1D) False 3 100;0;0 30.556 False ENSG00000102144 ENSG00000102144 HGNC:8896 PGM1 gene PGM1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycogen Storage Disease;Congenital disorder of deglycosylation 615273;Glycogen storage disease type XIV (Glycogen storage disorders);Congenital disorder of glycosylation, type It, 614921;Glycogen Storage Disorders- Muscle;Glycogen Storage Disease Type XIV;Glycogen storage disease XIV, 612934 27206562 False 3 100;0;0 30.556 False ENSG00000079739 ENSG00000079739 HGNC:8905 PGM2L1 gene PGM2L1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191 33979636 False 3 100;0;0 30.556 False ENSG00000165434 ENSG00000165434 HGNC:20898 PGM3 gene PGM3 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Immunodeficiency 23 24698316 False 3 0;0;0 30.556 False ENSG00000013375 ENSG00000013375 HGNC:8907 PGM3 gene PGM3 Victorian Clinical Genetics Services;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Immunodeficiency 23, 615816;Intellectual disability;Severe atopy, autoimmunity, bacterial and viral infections, skeletal anomalies dysplasia: short stature, brachydactyly, dysmorphic facial features, and intellectual disability cognitive impairment, hypomyelination 24589341;24698316;24931394;25529582 False 3 100;0;0 30.556 False ENSG00000013375 ENSG00000013375 HGNC:8907 PHACTR1 gene PHACTR1 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental and epileptic encephalopathy 70, OMIM:618298 30256902;28135719;23033978;27457812 False 3 25;0;75 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000112137 ENSG00000112137 HGNC:20990 PHF21A gene PHF21A Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Potocki-Shaffer syndrome, 601224;PSS;Intellectual disability;Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures, 618725 22770980;26333423;8456828;8882796;14872200;9489802;11017806;11903336;15852040;23239541;28127865;30487643 False 3 50;50;0 30.556 False ENSG00000135365 ENSG00000135365 HGNC:24156 PHF6 gene PHF6 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Borjeson-Forssman-Lehmann syndrome, OMIM:301900 15466013;15994862;12415272;25529582;24896178;24092917;25099957 False 3 100;0;0 30.556 False ENSG00000156531 ENSG00000156531 HGNC:18145 PHF8 gene PHF8 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation syndrome, X-linked, Siderius type, 300263;MENTAL RETARDATION SYNDROMIC X-LINKED SIDERIUS TYPE (MRXSSD) False 3 100;0;0 30.556 False ENSG00000172943 ENSG00000172943 HGNC:20672 PHGDH gene PHGDH Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Phosphoglycerate dehydrogenase deficiency, 601815;NEU-LAXOVA SYNDROME; NLS False 3 100;0;0 30.556 False ENSG00000092621 ENSG00000092621 HGNC:8923 PHGDH gene PHGDH Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neu-Laxova syndrome 1 256520;Phosphoglycerate dehydrogenase deficiency 601815 27604308;24816252;11055895;11034457;19235232;24836451;25152457 False 3 0;0;0 30.556 False ENSG00000092621 ENSG00000092621 HGNC:8923 PHIP gene PHIP Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted INTELLECTUAL DISABILITY;Developmental delay, intellectual disability, obesity, and dysmorphic features, 617991 29209020;23033978;27900362 False 3 33;0;67 30.556 False ENSG00000146247 ENSG00000146247 HGNC:15673 PHKA1 gene PHKA1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Muscle glycogenosis, 300559 27604308 False 3 100;0;0 30.556 False ENSG00000067177 ENSG00000067177 HGNC:8925 PHKA2 gene PHKA2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Glycogen Storage Disease;Glycogen Storage Disorders- Liver;Glycogen storage disease, type IXa2, 306000;Glycogen storage disease, type IXa1, 306000;hepatomegaly and mild hypoglycaemia;Glycogen storage disease type IX Hepatic phosphorylase kinase deficiency (Glycogen storage disorders) 27604308 False 3 0;0;0 30.556 False ENSG00000044446 ENSG00000044446 HGNC:8926 PHKB gene PHKB London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal hepatomegaly and variable myopathy;Glycogen Storage Disorders- Liver;Glycogen Storage Disorders- Muscle;Glycogen Storage Disease;Glycogen storage disease type IX Hepatic and muscle phosphorylase kinase deficiency (Glycogen storage disorders) 27604308 False 3 100;0;0 30.556 False ENSG00000102893 ENSG00000102893 HGNC:8927 PHKG2 gene PHKG2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal hepatomegaly and variable myopathy;Glycogen Storage Disorders- Liver;Glycogen Storage Disease;Glycogen storage disease IXc, 613027;Glycogen storage disease type IX Hepatic phosphorylase kinase deficiency with cirrhosis (Glycogen storage disorders);Cirrhosis due to liver phosphorylase kinase deficiency 27604308 False 3 0;0;0 30.556 False ENSG00000156873 ENSG00000156873 HGNC:8931 PHYH gene PHYH London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Refsum disease, 266500;Refsum disease (Disorders of peroxisomal alpha-, beta and omega-oxidation) 27604308 False 3 0;0;0 30.556 False ENSG00000107537 ENSG00000107537 HGNC:8940 PI4K2A gene PI4K2A Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, OMIM:620732 30564627;32418222;35880319 False 3 100;0;0 30.556 False ENSG00000155252 ENSG00000155252 HGNC:30031 PI4KA gene PI4KA Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, OMIM:616531 25855803;34415322;34415310 False 3 100;0;0 30.556 False ENSG00000241973 ENSG00000241973 HGNC:8983 PI4KA gene PI4KA Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, OMIM:616531 25855803;34415322;34415310 False 3 100;0;0 30.556 False ENSG00000241973 ENSG00000241973 HGNC:8983 PIBF1 gene PIBF1 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Joubert syndrome 33;OMIM #617767 26167768;30858804;29695797 False 3 100;0;0 30.556 False ENSG00000083535 ENSG00000083535 HGNC:23352 PIDD1 gene PIDD1 Expert Review Green;Other;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Global developmental delay;Intellectual disability;Seizures;Autism;Behavioral abnormality;Psychosis;Pachygyria;Lissencephaly;Abnormality of the corpus callosum 28397838;29302074;33414379;34163010 False 3 100;0;0 30.556 False ENSG00000177595 ENSG00000177595 HGNC:16491 PIGA gene PIGA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Multiple congenital anomalies-hypotonia-seizures syndrome 2 300868;PIGA-CDG (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation) 27604308 False 3 0;0;0 30.556 False ENSG00000165195 ENSG00000165195 HGNC:8957 PIGA gene PIGA Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2; MCAHS2 22305531 False 3 33;67;0 30.556 False ENSG00000165195 ENSG00000165195 HGNC:8957 PIGB gene PIGB Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental and epileptic encephalopathy 80, OMIM:618580 31256876 False 3 100;0;0 30.556 False ENSG00000069943 ENSG00000069943 HGNC:8959 PIGC gene PIGC Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycosylphosphatidylinositol biosynthesis defect 16, OMIM:617816 27694521;32707268 False 3 50;50;0 30.556 False ENSG00000135845 ENSG00000135845 HGNC:8960 PIGG gene PIGG Expert Review Green;Literature;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophy, OMIM:616917 28581210;26996948;30914295 False 3 100;0;0 30.556 False ENSG00000174227 ENSG00000174227 HGNC:25985 PIGH gene PIGH Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycosylphosphatidylinositol biosynthesis defect, 17 OMIM:618010;Hypotonia, moderate developmental delay, and autism, two episodes of febrile seizures 29603516;29573052;29603510 False 3 100;0;0 30.556 False ENSG00000100564 ENSG00000100564 HGNC:8964 PIGK gene PIGK Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures OMIM:618879 32220290 False 3 100;0;0 30.556 False ENSG00000142892 ENSG00000142892 HGNC:8965 PIGL gene PIGL London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal PIGL-CDG (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation);CHIME syndrome 280000 22444671 False 3 0;0;0 30.556 False ENSG00000108474 ENSG00000108474 HGNC:8966 PIGL gene PIGL Victorian Clinical Genetics Services;Expert Review Green;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Coloboma, Congenital Heart Disease, Ichthyosiform Dermatosis,Mental Retardation, and Ear Anomalies Syndrome;ZUNICH NEUROECTODERMAL SYNDROME False 3 100;0;0 30.556 False ENSG00000108474 ENSG00000108474 HGNC:8966 PIGM gene PIGM Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycosylphosphatidylinositol deficiency, OMIM:610293 27604308;16767100;25293775;17442906;31445883 False 3 67;0;33 30.556 False ENSG00000143315 ENSG00000143315 HGNC:18858 PIGN gene PIGN Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple congenital anomalies-hypotonia-seizures syndrome 1, 614080;MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME False 3 100;0;0 30.556 False ENSG00000197563 ENSG00000197563 HGNC:8967 PIGN gene PIGN London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal PIGN-CDG (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation);Multiple congenital anomalies-hypotonia-seizures syndrome 1 26419326;21493957 False 3 0;0;0 30.556 False ENSG00000197563 ENSG00000197563 HGNC:8967 PIGO gene PIGO London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperphosphatasia (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation);(Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation);Hyperphosphatasia with mental retardation syndrome 2 614749 27604308 False 3 0;0;0 30.556 False ENSG00000165282 ENSG00000165282 HGNC:23215 PIGO gene PIGO Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperphosphatasia with mental retardation syndrome 2, 614749;Hyperphosphatasia with Mental Retardation Syndrome;HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 2; HPMRS2 False 3 100;0;0 30.556 False ENSG00000165282 ENSG00000165282 HGNC:23215 PIGP gene PIGP Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental and epileptic encephalopathy 55, OMIM:617599 28334793;31139695;32042915 False 3 100;0;0 30.556 False ENSG00000185808 ENSG00000185808 HGNC:3046 PIGQ gene PIGQ Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple congenital anomalies-hypotonia-seizures syndrome-4 OMIM:618548 32588908;24463883;25558065;31148362 False 3 40;0;60 30.556 False ENSG00000007541 ENSG00000007541 HGNC:14135 PIGS gene PIGS Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycosylphosphatidylinositol biosynthesis defect 18 618143 30269814 False 3 100;0;0 30.556 False ENSG00000087111 ENSG00000087111 HGNC:14937 PIGS gene PIGS Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycosylphosphatidylinositol biosynthesis defect 18 618143 30269814 False 3 100;0;0 30.556 False ENSG00000087111 ENSG00000087111 HGNC:14937 PIGT gene PIGT Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal "Multiple congenital anomalies-hypotonia-seizures syndrome 3 615398" 24906948;28327575 False 3 33;67;0 30.556 False ENSG00000124155 ENSG00000124155 HGNC:14938 PIGT gene PIGT Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple congenital anomalies-hypotonia-seizures syndrome 3 23636107;28327575 False 3 100;0;0 30.556 False ENSG00000124155 ENSG00000124155 HGNC:14938 PIGU gene PIGU Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with brain anomalies, seizures, and scoliosis, OMIM:618590 31353022 False 3 100;0;0 30.556 False ENSG00000101464 ENSG00000101464 HGNC:15791 PIGV gene PIGV Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperphosphatasia with mental retardation syndrome 1, 239300;Hyperphosphatasia with Mental Retardation Syndrome;HYPERPHOSPHATASIA WITH MENTAL RETARDATION (HPMR) False 3 100;0;0 30.556 False ENSG00000060642 ENSG00000060642 HGNC:26031 PIGV gene PIGV London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperphosphatasia (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation);Hyperphosphatasia with mental retardation syndrome 1 239300;(Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation) 20802478;24129430 False 3 0;0;0 30.556 False ENSG00000060642 ENSG00000060642 HGNC:26031 PIGW gene PIGW Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Hyperphosphatasia with mental retardation syndrome 5 24367057 False 3 100;0;0 30.556 False ENSG00000184886 ENSG00000277161 HGNC:23213 PIGW gene PIGW Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycosylphosphatidylinositol biosynthesis defect 11, 616025 24367057;27626616;27626616;30078644 False 3 100;0;0 30.556 False ENSG00000184886 ENSG00000277161 HGNC:23213 PIK3CA gene PIK3CA Expert Review Green;Victorian Clinical Genetics Services;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic, 602501;Megalencephaly-capillary malformation-polymicrogyria syndrome, Orphanet:60040 False 3 100;0;0 30.556 False Other - please provide details in the comments ENSG00000121879 ENSG00000121879 HGNC:8975 PIK3R2 gene PIK3R2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387 False 3 100;0;0 30.556 False ENSG00000105647 ENSG00000105647 HGNC:8980 PINK1 gene PINK1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Parkinson disease 6, early onset 605909 27604308;15087508;16207731;18003639;18524835 False 3 0;0;0 30.556 False ENSG00000158828 ENSG00000158828 HGNC:14581 PIP5K1C gene PIP5K1C NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 37451268 False 3 100;0;0 30.556 False ENSG00000186111 ENSG00000186111 HGNC:8996 PITRM1 gene PITRM1 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spinocerebellar ataxia, autosomal recessive 30, OMIM:619405 26697887;29764912;29383861 False 3 100;0;0 30.556 True ENSG00000107959 ENSG00000107959 HGNC:17663 PITRM1 gene PITRM1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spinocerebellar ataxia, autosomal recessive 30, OMIM:619405 26697887;29383861;29764912 False 3 100;0;0 30.556 False ENSG00000107959 ENSG00000107959 HGNC:17663 PITRM1 gene PITRM1 Expert Review;Expert Review Green;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spinocerebellar ataxia, autosomal recessive 30, OMIM:619405 26697887;29764912;29383861 False 3 100;0;0 30.556 False ENSG00000107959 ENSG00000107959 HGNC:17663 PLA2G6 gene PLA2G6 Expert list;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Infantile neuroaxonal dystrophy 1 27604308;18570303;16783378;18799783 False 3 0;0;100 30.556 False ENSG00000184381 ENSG00000184381 HGNC:9039 PLA2G6 gene PLA2G6 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Infantile neuroaxonal dystrophy 1, 256600Neurodegeneration with brain iron accumulation 2B, 610217Parkinson disease 14, 612953;NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2B False 3 100;0;0 30.556 False ENSG00000184381 ENSG00000184381 HGNC:9039 PLA2G6 gene PLA2G6 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Infantile neuroaxonal dystrophy 1, OMIM:256600;neurodegeneration with brain iron accumulation 2A, MONDO:0024457;Neurodegeneration with brain iron accumulation 2B, OMIM:610217;neurodegeneration with brain iron accumulation 2B, MONDO:0012444;Parkinson disease 14, autosomal recessive, OMIM:612953;autosomal recessive Parkinson disease 14 MONDO:0013060 29903433;25348461;26001724;26506412;30528460;16783378;32357911 False 3 100;0;0 30.556 False ENSG00000184381 ENSG00000184381 HGNC:9039 PLAA gene PLAA Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, 617527;NDMSBA;Epileptic Encephalopathy 28413018;28007986 False 3 100;0;0 30.556 False ENSG00000137055 ENSG00000137055 HGNC:9043 PLCB1 gene PLCB1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epileptic encephalopathy, early infantile, 12, 613722;EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 12 False 3 100;0;0 30.556 False ENSG00000182621 ENSG00000182621 HGNC:15917 PLEKHG2 gene PLEKHG2 Expert Review Green;NHS GMS;Expert Review;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy and acquired microcephaly with or without dystonia, OMIM:616763;leukodystrophy and acquired microcephaly with or without dystonia;MONDO:0014766 26539891;24001768;26573021;34326120;35203342 False 3 33;67;0 30.556 False ENSG00000090924 ENSG00000090924 HGNC:29515 PLK1 gene PLK1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epilepsy;microcephaly;intellectual disability 33875846 False 3 100;0;0 30.556 False ENSG00000166851 ENSG00000166851 HGNC:9077 PLK4 gene PLK4 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MICROCEPHALY, GROWTH FAILURE AND RETINOPATHY 25344692 False 3 33;67;0 30.556 False ENSG00000142731 ENSG00000142731 HGNC:11397 PLP1 gene PLP1 Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Spastic paraplegia 2, X-linked 312920 Edit;Pelizaeus-Merzbacher disease 312080 25655951 False 3 0;0;0 30.556 False ENSG00000123560 ENSG00000123560 HGNC:9086 PLP1 gene PLP1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Pelizaeus-Merzbacher disease, 312080Spastic paraplegia 2, X-linked, 312920;LEUKODYSTROPHY HYPOMYELINATING TYPE 1 (HLD1) False 3 100;0;0 30.556 False ENSG00000123560 ENSG00000123560 HGNC:9086 PLPBP gene PLPBP Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epilepsy, early-onset, vitamin B6-dependent, 617290 27912044 False 3 0;100;0 30.556 False ENSG00000147471 ENSG00000147471 HGNC:9457 PLXNA1 gene PLXNA1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955;developmental and epileptic encephalopathy, MONDO:0100062 28464511;34054129;34415653 False 3 100;0;0 30.556 False ENSG00000114554 ENSG00000114554 HGNC:9099 PLXNB2 gene PLXNB2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal amelogenesis imperfecta, MONDO:0019507;sensorineural hearing loss disorder, MONDO:0020678;intellectual disability, MONDO:0001071 38458752 False 3 100;0;0 30.556 False ENSG00000196576 ENSG00000196576 HGNC:9104 PMM2 gene PMM2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Phosphomannomutase 2 deficiency (Disorders of protein N-glycosylation);Congenital disorder of glycosylation, type Ia 212065 11875054;11058895;11409861 False 3 0;0;0 30.556 False ENSG00000140650 ENSG00000140650 HGNC:9115 PMM2 gene PMM2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Ia, 212065;CONGENITAL DISORDERS OF GLYCOSYLATION False 3 100;0;0 30.556 False ENSG00000140650 ENSG00000140650 HGNC:9115 PMPCA gene PMPCA Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal slowly progressive cerebellar ataxia;non-progressive cerebellar ataxia 26657514;25808372 False 3 100;0;0 30.556 False ENSG00000165688 ENSG00000165688 HGNC:18667 PMPCA gene PMPCA Victorian Clinical Genetics Services;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal non-progressive cerebellar ataxia;slowly progressive cerebellar ataxia PMID: 25808372; PMID: 26657514 False 3 100;0;0 30.556 True ENSG00000165688 ENSG00000165688 HGNC:18667 PMPCB gene PMPCB Expert Review Green;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 6 OMIM:617954;multiple mitochondrial dysfunctions syndrome 6 MONDO:0054785 29576218 False 3 100;0;0 30.556 False ENSG00000105819 ENSG00000105819 HGNC:9119 PMPCB gene PMPCB Expert Review Green;Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 6 OMIM:617954;multiple mitochondrial dysfunctions syndrome 6 MONDO:0054785 29576218 False 3 0;0;0 30.556 False ENSG00000105819 ENSG00000105819 HGNC:9119 PMPCB gene PMPCB Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple mitochondrial dysfunctions syndrome 6 OMIM:617954;multiple mitochondrial dysfunctions syndrome 6 MONDO:0054785 29576218 False 3 0;0;0 30.556 False ENSG00000105819 ENSG00000105819 HGNC:9119 PNKP gene PNKP Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epileptic encephalopathy, early infantile, 10, 613402;EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 10 False 3 100;0;0 30.556 False ENSG00000039650 ENSG00000039650 HGNC:9154 PNP gene PNP Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Immunodeficiency due to purine nucleoside phosphorylase deficiency 613179 27604308;3029074;1384322;9067751;8931706;9737781;11453975 False 3 0;0;0 30.556 False ENSG00000198805 ENSG00000198805 HGNC:7892 PNPLA2 gene PNPLA2 Expert Review Green;NHS GMS;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neutral lipid storage disease with myopathy MIM#610717 18952067;21544567;25287355;25956450;32269696 False 3 100;0;0 30.556 False ENSG00000177666 ENSG00000177666 HGNC:30802 PNPLA6 gene PNPLA6 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Boucher-Neuhauser syndrome, 215470;Oliver-McFarlane syndrome, 275400;Trichomegaly-retina pigmentary degeneration-dwarfism syndrome 24355708;25033069; 25299038; 25480986;23733235 False 3 50;50;0 30.556 False ENSG00000032444 ENSG00000032444 HGNC:16268 PNPLA8 gene PNPLA8 Expert Review Green;Expert Review Green;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Mitochondrial myopathy with lactic acidosis, 251950 25473036;25512002;29681094 False 3 100;0;0 30.556 False ENSG00000135241 ENSG00000135241 HGNC:28900 PNPLA8 gene PNPLA8 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Mitochondrial myopathy with lactic acidosis, OMIM:251950;mitochondrial myopathy-lactic acidosis-deafness syndrome MONDO:0016825 39082157 False 3 100;0;0 30.556 False ENSG00000135241 ENSG00000135241 HGNC:28900 PNPLA8 gene PNPLA8 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Mitochondrial myopathy with lactic acidosis, 251950 29681094;25512002;25473036 False 3 100;0;0 30.556 False ENSG00000135241 ENSG00000135241 HGNC:28900 PNPO gene PNPO London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pyridoxamine 5 -oxidase deficiency (Disorders of pyridoxine metabolism) 27604308 False 3 0;0;0 30.556 False ENSG00000108439 ENSG00000108439 HGNC:30260 PNPT1 gene PNPT1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 13, OMIM:614932;Deafness, autosomal recessive 70, OMIM:614934;Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Multiple respiratory chain complex deficiencies (disorders of protein synthesis) 27604308 False 3 100;0;0 30.556 False ENSG00000138035 ENSG00000138035 HGNC:23166 PNPT1 gene PNPT1 Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 13, OMIM:614932;Combined oxidative phosphorylation defect type 13, MONDO:0013977 31752325 False 3 100;0;0 30.556 False ENSG00000138035 ENSG00000138035 HGNC:23166 PNPT1 gene PNPT1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 13, OMIM:614932;Deafness, autosomal recessive 70, OMIM:614934;Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Multiple respiratory chain complex deficiencies (disorders of protein synthesis) False 3 100;0;0 30.556 True ENSG00000138035 ENSG00000138035 HGNC:23166 PNPT1 gene PNPT1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 13, OMIM:614932 28594066;30046113;33199448 False 3 100;0;0 30.556 False ENSG00000138035 ENSG00000138035 HGNC:23166 POGZ gene POGZ Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted White-Sutton syndrome, OMIM:616364 25533962;26739615;26763879;26942287 False 3 100;0;0 30.556 False ENSG00000143442 ENSG00000143442 HGNC:18801 POLA1 gene POLA1 Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Pigmentary disorder, reticulate, with systemic manifestations, X-linked, 301220;XLPDR;X-Linked Intellectual Disability associated with short stature, microcephaly, and hypogonadism 15844784;27019227;19377476;31006512 False 3 25;0;75 30.556 False ENSG00000101868 ENSG00000101868 HGNC:9173 POLG gene POLG London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Progressive external ophthalmoplegia, autosomal dominant, 157640;Progressive external ophthalmoplegia, autosomal recessive, 258450;Mitochondrial DNA depletion syndrome 4A (Alpers type), 203700;Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions;Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Mitochondrial DNA depletion syndrome 4B (MNGIE type), 613662;Mitochondrial DNA depletion syndrome 4A (Alpers type);Mitochondrial DNA Depletion Syndrome;Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), 607459 27604308 False 3 100;0;0 30.556 False ENSG00000140521 ENSG00000140521 HGNC:9179 POLG gene POLG Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MITOCHONDRIAL DNA DEPLETION SYNDROME 4A (ALPERS TYPE) 0 False 3 33;67;0 30.556 False ENSG00000140521 ENSG00000140521 HGNC:9179 POLG gene POLG Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE);Mitochondrial DNA depletion syndrome 4A (Alpers type) 203700;Mitochondrial DNA depletion syndrome 4B (MNGIE type) 613662 False 3 0;0;0 30.556 False ENSG00000140521 ENSG00000140521 HGNC:9179 POLG gene POLG Victorian Clinical Genetics Services;Expert Review Green;Eligibility statement exclusion criteria;UKGTN;Radboud University Medical Center, Nijmegen;Expert Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Progressive external ophthalmoplegia, autosomal recessive, 258450;Progressive external ophthalmoplegia, autosomal dominant, 157640;Mitochondrial DNA depletion syndrome 4B (MNGIE type), 613662;Mitochondrial DNA depletion syndrome 4A (Alpers type), 203700;Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), 607459;Mitochondrial DNA Depletion Syndrome;Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions False 3 100;0;0 30.556 True ENSG00000140521 ENSG00000140521 HGNC:9179 POLG2 gene POLG2 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;UKGTN;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome syndrome 16 (hepatic type), OMIM:618528;Mitochondrial DNA depletion syndrome 16B (neuroophthalmic type), OMIM:619425;Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, OMIM:610131 27592148;30157269;21555342;31286721 False 3 100;0;0 30.556 False ENSG00000256525 ENSG00000256525 HGNC:9180 POLG2 gene POLG2 Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 27592148;30157269;21555342;31286721 False 3 0;0;0 30.556 False ENSG00000256525 ENSG00000256525 HGNC:9180 POLG2 gene POLG2 London North GLH;NHS GMS;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome syndrome 16 (hepatic type), OMIM:618528;Mitochondrial DNA depletion syndrome 16B (neuroophthalmic type), OMIM:619425;Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, OMIM:610131 16685652;21555342;27592148;30157269;31778857 False 3 100;0;0 30.556 False ENSG00000256525 ENSG00000256525 HGNC:9180 POLR1C gene POLR1C Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 11 False 3 0;0;0 30.556 False ENSG00000171453 ENSG00000171453 HGNC:20194 POLR1C gene POLR1C Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 11, OMIM:616494 26151409;32042905 False 3 100;0;0 30.556 False ENSG00000171453 ENSG00000171453 HGNC:20194 POLR2A gene POLR2A Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities, 618603;Global developmental delay;Generalized hypotonia;Feeding difficulties 31353023 False 3 100;0;0 30.556 False ENSG00000181222 ENSG00000181222 HGNC:9187 POLR3A gene POLR3A Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropichypogonadism, 607694;LEUKODYSTROPHY, HYPOMYELINATING, 7, WITH OR WITHOUT OLIGODONTIA AND/OR HYPOGONADOTROPIC HYPOGONADISM False 3 100;0;0 30.556 False ENSG00000148606 ENSG00000148606 HGNC:30074 POLR3A gene POLR3A Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism False 3 0;0;0 30.556 False ENSG00000148606 ENSG00000148606 HGNC:30074 POLR3B gene POLR3B NHS GMS;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:614381;POLR3B-related neurodevelopmental disorder;Ataxia, spasticity, and demyelinating neuropathy 22036171;22036172;24190003;25339210;26204956;27159321;32319736;33417887 False 3 100;0;0 30.556 False ENSG00000013503 ENSG00000013503 HGNC:30348 POLR3B gene POLR3B Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:614381 25655951 False 3 0;0;0 30.556 False ENSG00000013503 ENSG00000013503 HGNC:30348 POLRMT gene POLRMT Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 55, OMIM:619743;combined oxidative phosphorylation deficiency 55, MONDO:0859228 24386581;33602924;40583167 False 3 67;33;0 30.556 False ENSG00000099821 ENSG00000099821 HGNC:9200 POLRMT gene POLRMT Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 55, OMIM:619743;combined oxidative phosphorylation deficiency 55, MONDO:0859228 24386581;33602924;40583167 False 3 67;33;0 30.556 False ENSG00000099821 ENSG00000099821 HGNC:9200 POLRMT gene POLRMT Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 55, OMIM:619743;combined oxidative phosphorylation deficiency 55, MONDO:0859228 24386581;33602924;40583167 False 3 75;25;0 30.556 False ENSG00000099821 ENSG00000099821 HGNC:9200 POMGNT1 gene POMGNT1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;UKGTN Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3, 253280Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 3, 613151Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3, 613157;MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH MENTAL RETARDATION TYPE B3 (MDDGB3) False 3 100;0;0 30.556 False ENSG00000085998 ENSG00000085998 HGNC:19139 POMGNT1 gene POMGNT1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 253280;Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B;Muscular dystrophy-dystroglycanopathy (limb-girdle), type C 3 613157;Protein-O-mannose beta-1,2-N-acetyglucosaminyltransferase deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies);Retinitis pigmentosa 76 617123 27421908 False 3 0;0;0 30.556 False ENSG00000085998 ENSG00000085998 HGNC:19139 POMGNT2 gene POMGNT2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 22958903 False 3 33;67;0 30.556 False ENSG00000144647 ENSG00000144647 HGNC:25902 POMGNT2 gene POMGNT2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 27066570 False 3 0;0;0 30.556 False ENSG00000144647 ENSG00000144647 HGNC:25902 POMK gene POMK Expert Review Green;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 12 OMIM:616094;limb-girdle muscular dystrophy due to POMK deficiencyMONDO:0014489;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 OMIM:615249;muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 MONDO:0014101 23519211;24556084;24925318;29910097 False 3 100;0;0 30.556 False ENSG00000185900 ENSG00000185900 HGNC:26267 POMT1 gene POMT1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;UKGTN Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1, 236670Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1, 613155Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1, 609308;MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A1 (MDDGA1) False 3 100;0;0 30.556 False ENSG00000130714 ENSG00000130714 HGNC:9202 POMT1 gene POMT1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 613155;Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308;Protein-O-mannosyltransferase 1 deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies);Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670 27604308 False 3 0;0;0 30.556 False ENSG00000130714 ENSG00000130714 HGNC:9202 POMT2 gene POMT2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 613158;Protein-O-mannosyltransferase 2 deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies);Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150;Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 613156 27421908 False 3 0;0;0 30.556 False ENSG00000009830 ENSG00000009830 HGNC:19743 POMT2 gene POMT2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;UKGTN Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2, 613150Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2, 613156Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2, 613158;MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH MENTAL RETARDATION TYPE B2 (MDDGB2) False 3 100;0;0 30.556 False ENSG00000009830 ENSG00000009830 HGNC:19743 POR gene POR Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis 201750;Disordered steroidogenesis due to cytochrome P450 oxidoreductase 613571 27604308;14758361;15793702;15220035;15483095;16470797 False 3 0;0;0 30.556 False ENSG00000127948 ENSG00000127948 HGNC:9208 PORCN gene PORCN Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Focal dermal hypoplasia, 305600;FOCAL DERMAL HYPOPLASIA (FODH) False 3 100;0;0 30.556 False ENSG00000102312 ENSG00000102312 HGNC:17652 POU3F2 gene POU3F2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown neurodevelopmental delay with hyperphagic obesity 37207645 False 3 100;0;0 30.556 False ENSG00000184486 ENSG00000184486 HGNC:9215 POU3F3 gene POU3F3 Expert Review Green;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Snijders Blok-Fisher syndrome, 618604;Generalized hypotonia;Delayed speech and language development;Global developmental delay;Intellectual disability;Autistic behavior 31303265;24550763 False 3 100;0;0 30.556 False ENSG00000198914 ENSG00000198914 HGNC:9216 PPA2 gene PPA2 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 27523598 False 3 100;0;0 30.556 False ENSG00000138777 ENSG00000138777 HGNC:28883 PPA2 gene PPA2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sudden cardiac failure, infantile, 617222;Sudden cardiac failure, alcohol-induced, 617223 27523598 False 3 100;0;0 30.556 False ENSG00000138777 ENSG00000138777 HGNC:28883 PPFIBP1 gene PPFIBP1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 35830857;30214071 False 3 100;0;0 30.556 False ENSG00000110841 ENSG00000110841 HGNC:9249 PPFIBP1 gene PPFIBP1 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 35830857;30214071 False 3 100;0;0 30.556 False ENSG00000110841 ENSG00000110841 HGNC:9249 PPIL1 gene PPIL1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal PPIL1-related Neurodegenerative Pontocerebellar Hypoplasia with Microcephaly 33220177 False 3 100;0;0 30.556 False ENSG00000137168 ENSG00000137168 HGNC:9260 PPM1D gene PPM1D Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, 617450;IDDGIP 28343630;25529582;24896178 False 3 100;0;0 30.556 False ENSG00000170836 ENSG00000170836 HGNC:9277 PPOX gene PPOX Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Variegate porphyria, childhood-onset, OMIM:620483;variegate porphyria, MONDO:0008297 8290408;9811936;2004012;35164799;37879139;40114189;33159949 False 3 50;0;50 30.556 False ENSG00000143224 ENSG00000143224 HGNC:9280 PPOX gene PPOX NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Variegate porphyria, OMIM:176200;Variegate porphyria, childhood-onset, OMIM:620483;variegate porphyria, MONDO:0008297;variegate porphyria, childhood-onset, MONDO:0957577 9540991;9811936;10870850;12859407;25778941;30476629;32247286;33159949;35584894;37879139;38940544;40114189 False 3 67;0;33 30.556 False ENSG00000143224 ENSG00000143224 HGNC:9280 PPOX gene PPOX Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Variegate porphyria, OMIM:176200;Variegate porphyria, childhood-onset, OMIM:620483;variegate porphyria, MONDO:0008297;variegate porphyria, childhood-onset, MONDO:0957577 9540991;9811936;10870850;12859407;25778941;30476629;32247286;33159949;35584894;37879139;38940544;40114189 False 3 100;0;0 30.556 False ENSG00000143224 ENSG00000143224 HGNC:9280 PPP1CB gene PPP1CB Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Noonan syndrome-like disorder with loose anagen hair 2 617506 25529582;27868344;27264673;28211982 False 3 100;0;0 30.556 False ENSG00000213639 ENSG00000213639 HGNC:9282 PPP1R12A gene PPP1R12A Expert Review Green;Expert list Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Genitourinary and/or/brain malformation syndrome, 618820 31883643 False 3 100;0;0 30.556 False ENSG00000058272 ENSG00000058272 HGNC:7618 PPP1R15B gene PPP1R15B Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly, short stature, and impaired glucose metabolism 2, 616817 26159176;26307080;27640355 False 3 100;0;0 30.556 False ENSG00000158615 ENSG00000158615 HGNC:14951 PPP1R21 gene PPP1R21 Expert Review;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities, OMIM:619383 29808498;28940097;30520571 False 3 100;0;0 30.556 False ENSG00000162869 ENSG00000162869 HGNC:30595 PPP1R3F gene PPP1R3F NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 37531237 False 3 100;0;0 30.556 False ENSG00000049769 ENSG00000049769 HGNC:14944 PPP2CA gene PPP2CA Expert Review;Expert Review Green;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Abnormality of nervous system morphology;Seizures;Language impairment;Muscular hypotonia;Feeding difficulties;Intellectual disability;Neurodevelopmental disorder and language delay with or without structural brain abnormalities, 618354;Global developmental delay 29274472;30030003;30595372 False 3 100;0;0 30.556 False ENSG00000113575 ENSG00000113575 HGNC:9299 PPP2R1A gene PPP2R1A Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Houge-Janssens syndrome 2, OMIM:616362;Houge-Janssens syndrome 2, MONDO:0014605 25533962;33106617 False 3 100;0;0 30.556 False ENSG00000105568 ENSG00000105568 HGNC:9302 PPP2R2B gene PPP2R2B Expert Review Green;NHS GMS;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental syndrome 39565297;25356899 False 3 75;0;25 30.556 False ENSG00000156475 ENSG00000156475 HGNC:9305 PPP2R5C gene PPP2R5C Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Houge-Janssens syndrome 4, OMIM:621185 25972378;39696819;39978342 False 3 100;0;0 30.556 False ENSG00000078304 ENSG00000078304 HGNC:9311 PPP2R5D gene PPP2R5D Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted INTELLECTUAL DISABILITY 25533962 False 3 100;0;0 30.556 False ENSG00000112640 ENSG00000112640 HGNC:9312 PPP3CA gene PPP3CA Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Epileptic encephalopathy, infantile or early childhood, 1, 617711 28942967 False 3 100;0;0 30.556 False ENSG00000138814 ENSG00000138814 HGNC:9314 PPT1 gene PPT1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ceroid lipofuscinosis, neuronal, 1, 256730;NEURONAL CEROID LIPOFUSCINOSIS TYPE 1 (CLN1) False 3 100;0;0 30.556 False ENSG00000131238 ENSG00000131238 HGNC:9325 PPT1 gene PPT1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ceroid lipofuscinosis, neuronal, 1 27604308 False 3 0;0;0 30.556 False ENSG00000131238 ENSG00000131238 HGNC:9325 PQBP1 gene PQBP1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Renpenning syndrome, 309500;RENPENNING S(YNDROME 1 (RENS1) False 3 100;0;0 30.556 False ENSG00000102103 ENSG00000102103 HGNC:9330 PRDM13 gene PRDM13 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal congenital hypogonadotropic hypogonadism, MONDO:0015770;Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, OMIM:619761 34730112;35390279 False 3 67;33;0 30.556 False ENSG00000112238 ENSG00000112238 HGNC:13998 PRICKLE2 gene PRICKLE2 Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder;global developmental delay 34092786 False 3 67;0;33 30.556 False ENSG00000163637 ENSG00000163637 HGNC:20340 PRKAG2 gene PRKAG2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Cardiomyopathy, hypertrophic 6, 600858;Glycogen storage disease of heart, lethal congenital, 261740;Wolff-Parkinson-White syndrome, 194200 194200 False 3 100;0;0 30.556 False ENSG00000106617 ENSG00000106617 HGNC:9386 PRKAR1B gene PRKAR1B Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680 25414040;33833410 False 3 75;25;0 30.556 False ENSG00000188191 ENSG00000188191 HGNC:9390 PRMT7 gene PRMT7 Expert Review Green;Victorian Clinical Genetics Services;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal "Short stature, brachydactyly, intellectual developmental disability, and seizures 617157" False 3 100;0;0 30.556 False ENSG00000132600 ENSG00000132600 HGNC:25557 PRODH gene PRODH Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperprolinemia, type I, OMIM:239500;hyperprolinemia type 1, MONDO:0009400 27604308;24816252 False 3 100;0;0 30.556 False ENSG00000100033 ENSG00000100033 HGNC:9453 PRPF8 gene PRPF8 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted PRPF8-related developmental disorder (monoallelic);Retinitis pigmentosa 13, OMIM:600059 20811066;23714367;30420816;31696658;35543142 False 3 67;33;0 30.556 False ENSG00000174231 ENSG00000174231 HGNC:17340 PRPS1 gene PRPS1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Arts syndrome 301835;Charcot-Marie-Tooth disease, X-linked recessive, 5 311070;Deafness, X-linked 1 304500;Gout, PRPS-related 300661;Phosphoribosylpyrophosphate synthetase superactivity 300661 27604308 False 3 0;0;0 30.556 False ENSG00000147224 ENSG00000147224 HGNC:9462 PRPS1 gene PRPS1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Charcot-Marie-Tooth disease, X-linked recessive, 5, 311070;Arts syndrome, 301835;Deafness, X-linked 1, 304500;CHARCOT-MARIE-TOOTH DISEASE X-LINKED RECESSIVE TYPE 5 (CMTX5);Gout, PRPS-related, 300661;Phosphoribosylpyrophosphate synthetase superactivity, 300661 25529582;24896178 False 3 100;0;0 30.556 False ENSG00000147224 ENSG00000147224 HGNC:9462 PRR12 gene PRR12 Expert Review;Expert Review Green;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Global developmental delay, Intellectual disability, Abnormality of the iris, Abnormality of vision, Behavioral abnormality;Abnormality of the iris;Behavioral abnormality;Intellectual disability;Global developmental delay;Abnormality of vision 28135719;26163108;29556724 False 3 100;0;0 30.556 False ENSG00000126464 ENSG00000126464 HGNC:29217 PRSS12 gene PRSS12 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mental retardation, autosomal recessive 1, 249500;Mental Retardation, Recessive;MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 1 (MRT1) 12459588;25529582 False 3 80;20;0 30.556 False ENSG00000164099 ENSG00000164099 HGNC:9477 PRUNE1 gene PRUNE1 Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies OMIM:617481;neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies MONDO:0060490;NMIHBA;Complex neurological syndrome 26539891;28334956;33105479 False 3 100;0;0 30.556 False ENSG00000143363 ENSG00000143363 HGNC:13420 PSAP gene PSAP London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Atypical Gaucher disease;Metachromatic leukodystrophy due to SAP-b deficiency, 249900;Combined SAP deficiency;Combined SAP deficiency, 611721;Prosaposin deficiency (Sphingolipidoses);Atypical Krabbe disease;Gaucher disease, atypical, 610539;Krabbe disease, atypical, 611722 27604308 False 3 0;0;0 30.556 False ENSG00000197746 ENSG00000197746 HGNC:9498 PSAP gene PSAP Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined SAP deficiency 249900 False 3 0;0;0 30.556 False ENSG00000197746 ENSG00000197746 HGNC:9498 PSAP gene PSAP Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Metachromatic leukodystrophy due to SAP-b deficiency, 249900Gaucher disease, atypical, 610539Combined SAP deficiency, 611721Krabbe disease, atypical, 611722;ATYPICAL KRABBE DISEASE False 3 100;0;0 30.556 False ENSG00000197746 ENSG00000197746 HGNC:9498 PSAT1 gene PSAT1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Phosphoserine aminotransferase deficiency 610992;Neu-Laxova syndrome 2 616038 27604308;25152457;26960553;17436247 False 3 0;0;0 30.556 False ENSG00000135069 ENSG00000135069 HGNC:19129 PSMC3 gene PSMC3 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354;neurodevelopmental disorder, MONDO:0700092 32500975;37256937 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000165916 ENSG00000165916 HGNC:9549 PSMC5 gene PSMC5 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 33057194;38776958 False 3 67;33;0 30.556 False ENSG00000087191 ENSG00000087191 HGNC:9552 PSMD12 gene PSMD12 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Stankiewicz-Isidor syndrome, 617516;Syndromic Neurodevelopmental Disorder 28132691 False 3 100;0;0 30.556 False ENSG00000197170 ENSG00000197170 HGNC:9557 PSPH gene PSPH Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal PHOSPHOSERINE PHOSPHATASE DEFICIENCY 25152457 False 3 33;67;0 30.556 False ENSG00000146733 ENSG00000146733 HGNC:9577 PTBP1 gene PTBP1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder, MONDO:0700092 40965981 False 3 100;0;0 30.556 False ENSG00000011304 ENSG00000011304 HGNC:9583 PTCD3 gene PTCD3 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Combined oxidative phosphorylation deficiency 51, OMIM:619057;combined oxidative phosphorylation deficiency 51, MONDO:0033631 30607703;30706245;36450274 False 3 100;0;0 30.556 False ENSG00000132300 ENSG00000132300 HGNC:24717 PTCD3 gene PTCD3 NHS GMS;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Combined oxidative phosphorylation deficiency 51, OMIM:619057;combined oxidative phosphorylation deficiency 51, MONDO:0033631 30607703;30706245;36450274 False 3 100;0;0 30.556 False ENSG00000132300 ENSG00000132300 HGNC:24717 PTCH1 gene PTCH1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Holoprosencephaly 7, OMIM:610828 False 3 100;0;0 30.556 False ENSG00000185920 ENSG00000185920 HGNC:9585 PTCHD1 gene PTCHD1 Victorian Clinical Genetics Services;Expert Review Green;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females AUTISM/ID False 3 100;0;0 30.556 False ENSG00000165186 ENSG00000165186 HGNC:26392 PTDSS1 gene PTDSS1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted LENZ-MAJEWSKI HYPEROSTOTIC DWARFISM 24241535 False 3 50;50;0 30.556 False ENSG00000156471 ENSG00000156471 HGNC:9587 PTEN gene PTEN Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Cowden syndrome 1, 158350Lhermitte-Duclos syndrome, 158350Bannayan-Riley-Ruvalcaba syndrome, 153480{Meningioma}, 607174{Glioma susceptibility 2}, 613028Macrocephaly/autism syndrome, 605309PTEN hamartoma tumor syndromeVATER association with macrocephaly and ventriculomegaly, 276950{Prostate cancer, somatic}, 176807Thyroid carcinoma, follicular, somatic, 188470Malignant melanoma, somatic, 155600Endometrial carcinoma, somatic, 608089Squamous cell carcinoma, head and neck, somatic, 275355;PROTEUS SYNDROME False 3 100;0;0 30.556 False ENSG00000171862 ENSG00000171862 HGNC:9588 PTEN gene PTEN Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Cowden syndrome 1, OMIM:158350 29720545;29152901;30664625;30528446;32664367 False 3 100;0;0 30.556 False ENSG00000171862 ENSG00000171862 HGNC:9588 PTF1A gene PTF1A Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal DIABETES MELLITUS, PERMANENT NEONATAL, WITH CEREBELLAR AGENESIS 21749365;15543146;10507728 False 3 33;67;0 30.556 False ENSG00000168267 ENSG00000168267 HGNC:23734 PTPN11 gene PTPN11 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Noonan syndrome 1, 163950LEOPARD syndrome 1, 151100Leukemia, juvenile myelomonocytic, 607785Metachondromatosis, 156250;LEOPARD SYNDROME TYPE 1 False 3 100;0;0 30.556 False ENSG00000179295 ENSG00000179295 HGNC:9644 PTPN23 gene PTPN23 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental epileptic encephalopathy with hypomyelination and brain;Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity MIM#618890 atrophy;Intellectual disability;Severe developmental delay, 29899372;29090338;25558065 False 3 100;0;0 30.556 False ENSG00000076201 ENSG00000076201 HGNC:14406 PTPN4 gene PTPN4 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual disability, MONDO:0001071 17953619;25424712;30238967;https://doi.org/10.1016/j.xhgg.2021.100033 False 3 100;0;0 30.556 False ENSG00000088179 ENSG00000088179 HGNC:9656 PTRH2 gene PTRH2 Expert Review Green;NHS GMS;Expert Review;Expert Review;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Infantile-onset multisystem neurologic, endocrine, and pancreatic disease, OMIM:616263;neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1, MONDO:8000012 25574476;28175314;28328138;25558065;27129381;39176129;39766776 False 3 100;0;0 30.556 False ENSG00000141378 ENSG00000141378 HGNC:24265 PTRHD1 gene PTRHD1 Expert Review Green;Expert Review;Expert Review;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, OMIM:620747 30398675;27134041;27753167;29143421 False 3 50;50;0 30.556 True ENSG00000184924 ENSG00000184924 HGNC:33782 PTS gene PTS Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;6-Pyruvoyl-tetrahydropterin synthase deficiency (Disorders of pterin metabolism);Hyperphenylalaninemia, BH4-deficient, A 261640 27604308 False 3 0;0;0 30.556 False ENSG00000150787 ENSG00000150787 HGNC:9689 PTS gene PTS Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 6-PYRUVOYLTETRAHYDROPTERIN SYNTHASE DEFICIENCY 8178819;10220141;9450907 False 3 33;67;0 30.556 False ENSG00000150787 ENSG00000150787 HGNC:9689 PUF60 gene PUF60 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Syndromic intellectual disability;Verheij syndrome, 615583;VRJS;Chromosome 8q24.3 deletion syndrome;PUF60 syndrome;Intellectual disability 28327570; 27804958; 24140112 False 3 50;0;50 30.556 False ENSG00000179950 ENSG00000179950 HGNC:17042 PUM1 gene PUM1 Expert Review Green;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Spinocerebellar ataxia 47 617931 29474920;30903679;31859446;25768905 False 3 100;0;0 30.556 False ENSG00000134644 ENSG00000134644 HGNC:14957 PURA gene PURA Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted INTELLECTUAL DISABILITY 25342064 False 3 100;0;0 30.556 False ENSG00000185129 ENSG00000185129 HGNC:9701 PUS1 gene PUS1 Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Myopathy, lactic acidosis, and sideroblastic anemia 1, 600462;Mitochondrial myopathy and sideroblastic anemia 1; MLASA; Intellectual disability 28832011;26556812;25037980;25227147;21686963 False 3 33;0;67 30.556 False ENSG00000177192 ENSG00000177192 HGNC:15508 PUS1 gene PUS1 Expert Review Green;London North GLH;NHS GMS;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Mitochondrial myopathy and sideroblastic anemia 1, 600462 27604308 False 3 100;0;0 30.556 False ENSG00000177192 ENSG00000177192 HGNC:15508 PUS1 gene PUS1 Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Mitochondrial myopathy and sideroblastic anemia 1, 600462 15108122;15772074;28832011;26556812 False 3 100;0;0 30.556 False ENSG00000177192 ENSG00000177192 HGNC:15508 PUS3 gene PUS3 Expert Review;Expert Review Green;Expert Review;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with microcephaly and gray sclerae, OMIM:617051 30697592;30308082;27055666 False 3 0;100;0 30.556 False ENSG00000110060 ENSG00000110060 HGNC:25461 PUS7 gene PUS7 Expert Review;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature, 618342;Short stature;Microcephaly;Intellectual disability;Behavioral abnormality 30778726;30526862 False 3 100;0;0 30.556 False ENSG00000091127 ENSG00000091127 HGNC:26033 PYCR1 gene PYCR1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cutis laxa, autosomal recessive, type IIB, 612940;Cutis laxa, autosomal recessive, type IIb/IIIb (Disorders of ornithine or proline metabolism);Cutis laxa, autosomal recessive, type IIIB, 614438 27604308 False 3 50;0;50 30.556 False ENSG00000183010 ENSG00000183010 HGNC:9721 PYCR1 gene PYCR1 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cutis laxa, autosomal recessive, type IIB, 612940;ARCL2B;Intellectual disability 27756598;19401719;27796797;26516448 False 3 25;25;50 30.556 False ENSG00000183010 ENSG00000183010 HGNC:9721 PYCR2 gene PYCR2 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 10, 616420; intellectual disability;Postnatal microcephaly, hypomyelination, and reduced cerebral white-matter volume 25865492;27130255; 27860360 False 3 33;67;0 30.556 False ENSG00000143811 ENSG00000143811 HGNC:30262 PYCR2 gene PYCR2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 10 616420 False 3 0;0;0 30.556 False ENSG00000143811 ENSG00000143811 HGNC:30262 PYGL gene PYGL London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycogen Storage Disease;Glycogen Storage Disorders- Liver;Glycogen storage disease VI, 232700;hepatomegaly and mild hypoglycaemia;Glycogen Storage Disease Type VI;Glycogen storage disease type VI, Hers (Glycogen storage disorders) 27604308 False 3 0;0;0 30.556 False ENSG00000100504 ENSG00000100504 HGNC:9725 PYGM gene PYGM London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycogen storage disease type V, McArdle (Glycogen storage disorders);McArdle disease 232600 27604308 False 3 100;0;0 30.556 False ENSG00000068976 ENSG00000068976 HGNC:9726 QARS gene QARS Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy, 615760;Intellectual disability 28620870;24656866;25041233; 25471517;25432320;24709618 False 3 50;50;0 30.556 False ENSG00000172053 ENSG00000172053 HGNC:9751 QARS gene QARS Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy, OMIM:615760 28620870;25471517;25432320;25041233;24656866;32042906 False 3 67;33;0 30.556 False ENSG00000172053 ENSG00000172053 HGNC:9751 QARS gene QARS Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy, OMIM:615760;Multiple respiratory chain complex deficiencies (disorders of protein synthesis) 28620870;25471517;25432320;25041233;24656866;32042906 False 3 100;0;0 30.556 True ENSG00000172053 ENSG00000172053 HGNC:9751 QDPR gene QDPR London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperphenylalaninemia, BH4-deficient, C 27604308 False 3 0;0;0 30.556 False ENSG00000151552 ENSG00000151552 HGNC:9752 QDPR gene QDPR Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal BH4-DEFICIENT HYPERPHENYLALANINEMIA C 9744478;9341885;2116088;8326489;11153907 False 3 33;67;0 30.556 False ENSG00000151552 ENSG00000151552 HGNC:9752 QRICH1 gene QRICH1 Victorian Clinical Genetics Services;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Ververi-Brady syndrome, 617982;Intellectual disability 28692176;25529582 False 3 100;0;0 30.556 False ENSG00000198218 ENSG00000198218 HGNC:24713 QRSL1 gene QRSL1 Expert Review Green;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 40, OMIM:618835 26741492;29440775;30283131 False 3 100;0;0 30.556 False ENSG00000130348 ENSG00000130348 HGNC:21020 QRSL1 gene QRSL1 Expert Review Green;Victorian Clinical Genetics Services;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 40, OMIM:618835 26741492;29440775;30283131 False 3 100;0;0 30.556 False ENSG00000130348 ENSG00000130348 HGNC:21020 RAB11A gene RAB11A Expert Review Green;NHS GMS;Expert Review;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Global developmental delay, HP:0001263;Intellectual disability, HP:0001249 29100083;33875846 False 3 67;33;0 30.556 False ENSG00000103769 ENSG00000103769 HGNC:9760 RAB11B gene RAB11B Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter, OMIM:617807 19344873;29106825 False 3 100;0;0 30.556 False ENSG00000185236 ENSG00000185236 HGNC:9761 RAB11B gene RAB11B Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter, OMIM:617807 29106825 False 3 100;0;0 30.556 False ENSG00000185236 ENSG00000185236 HGNC:9761 RAB18 gene RAB18 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Warburg micro syndrome 3, 614222;WARBURG MICRO SYNDROME TYPE 3 False 3 100;0;0 30.556 False ENSG00000099246 ENSG00000099246 HGNC:14244 RAB23 gene RAB23 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ACROCEPHALOPOLYSYNDACTYLY TYPE 2 17503333;20358613 False 3 33;67;0 30.556 False ENSG00000112210 ENSG00000112210 HGNC:14263 RAB39B gene RAB39B Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Intellectual developmental disorder, X-linked 72, OMIM:300271;Waisman syndrome, OMIM:311510 20159109;25434005;11050621;29152164;32873259;34761259 False 3 100;0;0 30.556 False ENSG00000155961 ENSG00000155961 HGNC:16499 RAB3GAP1 gene RAB3GAP1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Warburg micro syndrome 1, 600118;WARBURG MICRO SYNDROME TYPE 1 False 3 100;0;0 30.556 False ENSG00000115839 ENSG00000115839 HGNC:17063 RAB3GAP2 gene RAB3GAP2 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Martsolf syndrome 1, OMIM:212720;Warburg micro syndrome 2, OMIM:614225 False 3 100;0;0 30.556 False ENSG00000118873 ENSG00000118873 HGNC:17168 RAB5C gene RAB5C NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder MONDO:0700092, RAB5C-related 37552066 False 3 100;0;0 30.556 False ENSG00000108774 ENSG00000108774 HGNC:9785 RAC1 gene RAC1 Victorian Clinical Genetics Services;Literature;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown intellectual disability; developmental delay 27479843; 28886345 False 3 0;100;0 30.556 False ENSG00000136238 ENSG00000136238 HGNC:9801 RAC3 gene RAC3 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, OMIM:618577 29276006;30293988;35851598;35595279 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000169750 ENSG00000169750 HGNC:9803 RAD21 gene RAD21 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Cornelia de Lange syndrome 4, OMIM:614701 22633399;30716475;24378232;27882533;27620904;31334757;32193685 False 3 100;0;0 30.556 False ENSG00000164754 ENSG00000164754 HGNC:9811 RAF1 gene RAF1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Noonan syndrome 5, 611553LEOPARD syndrome 2, 611554;NOONAN SYNDROME 5 False 3 100;0;0 30.556 False ENSG00000132155 ENSG00000132155 HGNC:9829 RAI1 gene RAI1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Immunodeficiency 9, 612782;SMITH-MAGENIS SYNDROME (SMS) False 3 100;0;0 30.556 False ENSG00000108557 ENSG00000108557 HGNC:9834 RALA gene RALA Expert Review;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Global developmental delay;Seizures;Abnormality of nervous system morphology;Global developmental delay, Intellectual disability, Seizures, Abnormality of nervous system morphology;Intellectual disability 30500825 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000006451 ENSG00000006451 HGNC:9839 RALGAPA1 gene RALGAPA1 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation 618797 32004447 False 3 100;0;0 30.556 False ENSG00000174373 ENSG00000174373 HGNC:17770 RAP1B gene RAP1B NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies, OMIM:620654;Syndromic intellectual disability 26280580;32627184;35451551 False 3 100;0;0 30.556 False ENSG00000127314 ENSG00000127314 HGNC:9857 RARB gene RARB Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Microphthalmia, syndromic 12, OMIM:615524;neurodevelopmental disorder, MONDO:0700092 17506106;24075189;25457163;27120018;30281527;30880327 False 3 50;50;0 30.556 False ENSG00000077092 ENSG00000077092 HGNC:9865 RARS gene RARS Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 9, OMIM:616140 31814314;28905880;24777941;30500859 False 3 0;0;0 30.556 False ENSG00000113643 ENSG00000113643 HGNC:9870 RARS gene RARS Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 9, OMIM:616140 31814314;28905880;24777941;30500859 False 3 100;0;0 30.556 False ENSG00000113643 ENSG00000113643 HGNC:9870 RARS2 gene RARS2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Pontocerebellar hypoplasia, type 6, 611523 False 3 100;0;0 30.556 True ENSG00000146282 ENSG00000146282 HGNC:21406 RARS2 gene RARS2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pontocerebellar hypoplasia, type 6, 611523;Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) 27604308 False 3 100;0;0 30.556 False ENSG00000146282 ENSG00000146282 HGNC:21406 RARS2 gene RARS2 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pontocerebellar hypoplasia, type 6, 611523;PONTOCEREBELLAR HYPOPLASIA TYPE 6 25529582;24896178 False 3 100;0;0 30.556 False ENSG00000146282 ENSG00000146282 HGNC:21406 RBBP5 gene RBBP5 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 39036895 False 3 100;0;0 30.556 False ENSG00000117222 ENSG00000117222 HGNC:9888 RBBP8 gene RBBP8 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Jawad syndrome, 251255;Microcephaly with mental retardation and digital anomalies;Seckel syndrome, 24389050;growth retardation, microcephaly with mental retardation, and a characteristic facial appearance 18071751;21998596;24389050;11781686 False 3 50;50;0 30.556 False ENSG00000101773 ENSG00000101773 HGNC:9891 RBCK1 gene RBCK1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Polyglucosan body myopathy 1 with or without immunodeficiency, OMIM:615895 23889995;23104095 False 3 100;0;0 30.556 False ENSG00000125826 ENSG00000125826 HGNC:15864 RBL2 gene RBL2 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Brunet-Wagner neurodevelopmental syndrome, OMIM:619690 33980986;32105419;9806916 False 3 67;0;33 30.556 False ENSG00000103479 ENSG00000103479 HGNC:9894 RBM10 gene RBM10 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females TARP syndrome, 311900;TARP SYNDROME False 3 100;0;0 30.556 False ENSG00000182872 ENSG00000182872 HGNC:9896 RBP4 gene RBP4 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Retinol binding protein deficiency (Other disorders of vitamins and cofactors);Posterior segment abnormalities 27604308 False 3 0;0;0 30.556 False ENSG00000138207 ENSG00000138207 HGNC:9922 RBSN gene RBSN Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Kariminejad-Reversade neurodevelopmental syndrome, OMIM:620937;Myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalities, OMIM:620939 25233840;29784638;35652444 False 3 100;0;0 30.556 False ENSG00000131381 ENSG00000131381 HGNC:20759 RELN gene RELN NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Lissencephaly 2 (Norman-Roberts type), OMIM:257320;neurodevelopmental disorder, MONDO:0700092 35769015 False 3 100;0;0 30.556 False ENSG00000189056 ENSG00000189056 HGNC:9957 RERE gene RERE Expert Review Green;Victorian Clinical Genetics Services;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart 616975 27087320;25529582 False 3 100;0;0 30.556 False ENSG00000142599 ENSG00000142599 HGNC:9965 RFT1 gene RFT1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type In, 612015;CONGENITAL DISORDER OF GLYCOSYLATION TYPE 1N False 3 0;100;0 30.556 False ENSG00000163933 ENSG00000163933 HGNC:30220 RFT1 gene RFT1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type In 612015;Flippase of Man5GlcNAc2-PP-Dol deficiency (Disorders of protein N-glycosylation) 27604308 False 3 0;0;0 30.556 False ENSG00000163933 ENSG00000163933 HGNC:30220 RFX3 gene RFX3 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual disability, MONDO:0001071;Autism spectrum disorder, MONDO:0005258;Attention deficit-hyperactivity disorder, MONDO:0007743 33658631 False 3 100;0;0 30.556 False ENSG00000080298 ENSG00000080298 HGNC:9984 RFX4 gene RFX4 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual disability, MONDO:0001071;Autism spectrum disorder, MONDO:0005258 33658631 False 3 100;0;0 30.556 False ENSG00000111783 ENSG00000111783 HGNC:9985 RFX7 gene RFX7 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities, OMIM:620330 33658631 False 3 100;0;0 30.556 False ENSG00000181827 ENSG00000181827 HGNC:25777 RHOBTB2 gene RHOBTB2 Expert Review Green;Literature;Expert Review Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Developmental and epileptic encephalopathy 64, OMIM:618004;developmental and epileptic encephalopathy, 64, MONDO:0033373 29276004;29768694;26740508;37165955 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000008853 ENSG00000008853 HGNC:18756 RIT1 gene RIT1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Noonan syndrome 8, 615355;NOONAN SYNDROME 8 False 3 100;0;0 30.556 False ENSG00000143622 ENSG00000143622 HGNC:10023 RLIM gene RLIM Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked 61, 300978; Intellectual disability 25644381;25735484;19945382 False 3 33;0;67 30.556 False ENSG00000131263 ENSG00000131263 HGNC:13429 RMND1 gene RMND1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 11, 614922;ENCEPHALOPATHY ASSOCIATED WITH MULTIPLE OXIDATIVE PHOSPHORYLATION COMPLEX DEFICIENCIES AND A MITOCHONDRIAL TRANSLATION DEFECT False 3 100;0;0 30.556 False ENSG00000155906 ENSG00000155906 HGNC:21176 RMND1 gene RMND1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 11, 614922;Encephalopathy associated with multiple oxidative phosphorylation complex deficiencies and a mitochondrial translation defect 27604308 False 3 100;0;0 30.556 False ENSG00000155906 ENSG00000155906 HGNC:21176 RMND1 gene RMND1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 11, 614922;Encephalopathy associated with multiple oxidative phosphorylation complex deficiencies and a mitochondrial translation defect False 3 100;0;0 30.556 True ENSG00000155906 ENSG00000155906 HGNC:21176 RNASEH1 gene RNASEH1 Victorian Clinical Genetics Services;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2 Reyes et al., 2005, Am. J. Hum. Genet., 97, 186-193. False 3 100;0;0 30.556 True ENSG00000171865 ENSG00000171865 HGNC:18466 RNASEH1 gene RNASEH1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2 Reyes et al., 2005, Am. J. Hum. Genet., 97, 186-193. False 3 100;0;0 30.556 False ENSG00000171865 ENSG00000171865 HGNC:18466 RNASEH2A gene RNASEH2A Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;Intracerebral calcification disorders;(Disorders of nucleotide metabolism, Aicardi-Gouti res Syndrome) AGS4;Inherited white matter disorders 27604308 False 3 100;0;0 30.556 False ENSG00000104889 ENSG00000104889 HGNC:18518 RNASEH2A gene RNASEH2A Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Aicardi-Goutieres syndrome 4;Aicardi-Goutieres Syndrome;General Leukodystrophy & Mitochondrial Leukoencephalopathy 25604658 False 3 0;0;0 30.556 False ENSG00000104889 ENSG00000104889 HGNC:18518 RNASEH2A gene RNASEH2A Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Aicardi-Goutieres syndrome 4, 610333;AICARDI-GOUTIERES SYNDROME 4 False 3 100;0;0 30.556 False ENSG00000104889 ENSG00000104889 HGNC:18518 RNASEH2B gene RNASEH2B Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Aicardi-Goutieres syndrome 2, OMIM:610181 False 3 100;0;0 30.556 False ENSG00000136104 ENSG00000136104 HGNC:25671 RNASEH2B gene RNASEH2B Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Aicardi-Goutieres syndrome 2, OMIM:610181 25604658 False 3 0;0;0 30.556 False ENSG00000136104 ENSG00000136104 HGNC:25671 RNASEH2B gene RNASEH2B Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Aicardi-Goutieres syndrome 2, OMIM:610181 27604308 False 3 100;0;0 30.556 False ENSG00000136104 ENSG00000136104 HGNC:25671 RNASEH2C gene RNASEH2C Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Aicardi-Goutieres Syndrome 3;Aicardi-Goutieres Syndrome;General Leukodystrophy & Mitochondrial Leukoencephalopathy;Aicardi-Goutieres syndrome 3 25604658 False 3 0;0;0 30.556 False ENSG00000172922 ENSG00000172922 HGNC:24116 RNASEH2C gene RNASEH2C Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;(Disorders of nucleotide metabolism, Aicardi-Gouti res Syndrome) AGS3;Intracerebral calcification disorders;Inherited white matter disorders 27604308 False 3 100;0;0 30.556 False ENSG00000172922 ENSG00000172922 HGNC:24116 RNASEH2C gene RNASEH2C Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Aicardi-Goutieres syndrome 3, 610329;AICARDI-GOUTIERES SYNDROME 3 False 3 100;0;0 30.556 False ENSG00000172922 ENSG00000172922 HGNC:24116 RNASET2 gene RNASET2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukoencephalopathy, cystic, without megalencephaly False 3 0;0;0 30.556 False ENSG00000026297 ENSG00000026297 HGNC:21686 RNASET2 gene RNASET2 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukoencephalopathy, cystic, without megalencephaly, 612951;LEUKOENCEPHALOPATHY, CYSTIC, WITHOUT MEGALENCEPHALY False 3 100;0;0 30.556 False ENSG00000026297 ENSG00000026297 HGNC:21686 RNF113A gene RNF113A Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Trichothiodystrophy 5, nonphotosensitive, OMIM:300953 25612912;29144457;31880405;31793730;29133357;30506991;15256591;24026126;23555887 False 3 25;0;75 30.556 False ENSG00000125352 ENSG00000125352 HGNC:12974 RNF125 gene RNF125 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Tenorio syndrome, 616260;Intellectual disability 25196541 False 3 100;0;0 30.556 False ENSG00000101695 ENSG00000101695 HGNC:21150 RNF13 gene RNF13 Expert Review Green;Expert Review;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Developmental and epileptic encephalopathy 73, OMIM:618379 30595371 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000082996 ENSG00000082996 HGNC:10057 RNF220 gene RNF220 Expert Review Green;NHS GMS;Literature;Other Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, MONDO:0019046;Abnormal corpus callosum morphology, HP:0001273 33964137;10881263 False 3 100;0;0 30.556 False ENSG00000187147 ENSG00000187147 HGNC:25552 RNU2-2P gene RNU2-2P Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental and epileptic encephalopathy 119, OMIM:621304 40210679;40442284 False 3 67;0;33 30.556 False ENSG00000222328 ENSG00000222328 HGNC:10152 RNU4-2 gene RNU4-2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted ReNU syndrome, OMIM:620851 38821540;38645094;38991538 False 3 100;0;0 30.556 False ENSG00000202538 ENSG00000202538 HGNC:10193 RNU5B-1 gene RNU5B-1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with seizures and joint laxity, OMIM:621302;RNU5B-1 related neurodevelopmental disorder with seizures and joint laxity, MONDO:1060179 40379786;40442284 False 3 100;0;0 30.556 False ENSG00000200156 ENSG00000200156 HGNC:10212 RNU7-1 gene RNU7-1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Aicardi-Goutieres syndrome 9, OMIM:619487;Type I interferonopathy 33230297 False 3 100;0;0 30.556 False ENSG00000238923 ENSG00000238923 HGNC:34033 RNU7-1 gene RNU7-1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Aicardi-Goutieres syndrome 9, OMIM:619487;Type I interferonopathy 33230297 False 3 100;0;0 30.556 False ENSG00000238923 ENSG00000238923 HGNC:34033 ROBO1 gene ROBO1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability, MONDO:0001071;Neurooculorenal syndrome, OMIM:620305 35348658;35227688;34193621;31448886;30692597;29194579;28592524;28402530;28286008 False 3 67;33;0 30.556 False ENSG00000169855 ENSG00000169855 HGNC:10249 ROGDI gene ROGDI Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Kohlschutter-Tonz syndrome, 226750;KOHLSCH TTER-T _NZ SYNDROME False 3 100;0;0 30.556 False ENSG00000067836 ENSG00000067836 HGNC:29478 RORA gene RORA Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual developmental disorder with or without epilepsy or cerebellar ataxia, 618060 29656859 False 3 0;100;0 30.556 False ENSG00000069667 ENSG00000069667 HGNC:10258 RPGRIP1L gene RPGRIP1L Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Joubert syndrome 7, 611560Meckel syndrome 5, 611561COACH syndrome, 216360;COACH SYNDROME (COACHS) False 3 100;0;0 30.556 False ENSG00000103494 ENSG00000103494 HGNC:29168 RPIA gene RPIA Expert Review;Expert Review Green;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ribose 5-phosphate isomerase deficiency, OMIM:608611 20499043;31056085;14988808;30088433;28801340 False 3 100;0;0 30.556 False ENSG00000153574 ENSG00000153574 HGNC:10297 RPIA gene RPIA London North GLH;NHS GMS;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ribose-5-phosphate isomerase deficiency (Disorders of pentose metabolism);Ribose 5-phosphate isomerase deficiency, OMIM:608611 27604308;30088433;14988808;28801340 False 3 0;0;100 30.556 False ENSG00000153574 ENSG00000153574 HGNC:10297 RPIA gene RPIA Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ribose 5-phosphate isomerase deficiency, OMIM:608611 14988808;28801340;30088433;31056085;31247379 False 3 100;0;0 30.556 False ENSG00000153574 ENSG00000153574 HGNC:10297 RPL10 gene RPL10 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Intellectual developmental disorder, X-linked syndromic 35, OMIM:300998 25316788;25316788;25316788;35876338 False 3 60;0;40 30.556 False ENSG00000147403 ENSG00000147403 HGNC:10298 RPL10 gene RPL10 Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked, syndromic, 35 25316788 False 3 100;0;0 30.556 False ENSG00000147403 ENSG00000147403 HGNC:10298 RPS6KA3 gene RPS6KA3 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Coffin-Lowry syndrome, OMIM:303600;Intellectual developmental disorder, X-linked 19, OMIM:300844 14986828;9837815;10094187;9887375;8955270;17717706;15214012;11992250;12439904;10528858;12210291;12030896;12558110;17318637 False 3 100;0;0 30.556 False ENSG00000177189 ENSG00000177189 HGNC:10432 RREB1 gene RREB1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted RASopathy, MONDO:0021060 38332451;40418122 False 3 100;0;0 30.556 False ENSG00000124782 ENSG00000124782 HGNC:10449 RRM2B gene RRM2B Victorian Clinical Genetics Services;UKGTN;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Disorders of mitochondrial DNA maintenance and integrity;Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075;Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5, 613077;Mitochondrial DNA depletion syndrome 8B (MNGIE type), 612075;Mitochondrial DNA Depletion Syndrome (recessive) False 3 100;0;0 30.556 False ENSG00000048392 ENSG00000048392 HGNC:17296 RRM2B gene RRM2B London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5, 613077;Mitochondrial DNA depletion syndrome 8B (MNGIE type), 612075;Mitochondrial DNA Depletion Syndrome (recessive);Mitochondrial Ribonucelotide Reductase subunit 2 deficiency (Disorders of purine metabolism);Progressive external ophthalmoplegia with mitochondrial DNA deletions (autosomal dominant);Disorders of mitochondrial DNA maintenance and integrity;Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075 27604308 False 3 100;0;0 30.556 False ENSG00000048392 ENSG00000048392 HGNC:17296 RRM2B gene RRM2B Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 8B (MNGIE type), 612075; Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075;Mitochondrial depletion syndrome; Intellectual disability 23107649; 17486094; 19138848;19667227; 21378381 False 3 100;0;0 30.556 False ENSG00000048392 ENSG00000048392 HGNC:17296 RRM2B gene RRM2B Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) 25655951 False 3 0;0;0 30.556 False ENSG00000048392 ENSG00000048392 HGNC:17296 RSPRY1 gene RSPRY1 Expert Review Green;NHS GMS;Literature;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, OMIM:616723 26365341;30063090;38562122;39940902 False 3 100;0;0 30.556 False ENSG00000159579 ENSG00000159579 HGNC:29420 RSRC1 gene RSRC1 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder, autosomal recessive 70 618402 28640246;29522154;32227164 False 3 100;0;0 30.556 False ENSG00000174891 ENSG00000174891 HGNC:24152 RTEL1 gene RTEL1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 5 23453664 False 3 33;67;0 30.556 False ENSG00000258366 ENSG00000258366 HGNC:15888 RTN4IP1 gene RTN4IP1 Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Optic atrophy 10, with or without ataxia, mental retardation, and seizures 5529582;29181510;26593267 False 3 50;50;0 30.556 False ENSG00000130347 ENSG00000130347 HGNC:18647 RTN4IP1 gene RTN4IP1 Expert Review Green;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Optic atrophy 10 with or without ataxia, mental retardation, and seizures 616732 28638143;26593267;29181510 False 3 100;0;0 30.556 False ENSG00000130347 ENSG00000130347 HGNC:18647 RTN4IP1 gene RTN4IP1 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Optic atrophy 10 with or without ataxia, mental retardation, and seizures 616732 26593267;29181510;28638143 False 3 100;0;0 30.556 False ENSG00000130347 ENSG00000130347 HGNC:18647 RTTN gene RTTN Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly, short stature, and polymicrogyria with seizures, 614833; Intellectual disability 26846091; 26608784;22939636 False 3 50;50;0 30.556 False ENSG00000176225 ENSG00000176225 HGNC:18654 SACS gene SACS Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic ataxia, Charlevoix-Saguenay type;Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) 12873855 (18 patients from 4 families);15985586 (two siblings);14718706 (two sisters);16606928 (case study);10655055 (17 families with 24 patients);14718708 (two family members) False 3 100;0;0 30.556 False ENSG00000151835 ENSG00000151835 HGNC:10519 SACS gene SACS Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS);Spastic ataxia, Charlevoix-Saguenay type PMID: 10655055 (17 families with 24 patients);PMID: 16606928 (case study);PMID: 15985586 (two siblings);PMID: 14718708 (two family members);PMID: 14718706 (two sisters);PMID: 12873855 (18 patients from 4 families) False 3 100;0;0 30.556 True ENSG00000151835 ENSG00000151835 HGNC:10519 SAMD9 gene SAMD9 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown MIRAGE syndrome, 617053 27182967 False 3 100;0;0 30.556 False Other - please provide details in the comments ENSG00000205413 ENSG00000205413 HGNC:1348 SAMHD1 gene SAMHD1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal AICARDI-GOUTIERES SYNDROME PMID: 19525956 False 3 33;67;0 30.556 False ENSG00000101347 ENSG00000101347 HGNC:15925 SAMHD1 gene SAMHD1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal (Disorders of nucleotide metabolism, Aicardi-Goutieres Syndrome) AGS5;Aicardi-Goutieres syndrome-5 (AGS5);Aicardi-Goutieres syndrome 5, 612952 PMID: 19525956;25604658 False 3 50;0;50 30.556 False ENSG00000101347 ENSG00000101347 HGNC:15925 SAMHD1 gene SAMHD1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Aicardi-Goutieres Syndrome;General Leukodystrophy & Mitochondrial Leukoencephalopathy;Aicardi-Goutieres syndrome 25604658 False 3 0;0;0 30.556 False ENSG00000101347 ENSG00000101347 HGNC:15925 SAR1B gene SAR1B London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Anderson disease (Inherited hypolipidaemias);CHYLOMICRON RETENTION DISEASE 246700 27604308 False 3 100;0;0 30.556 False ENSG00000152700 ENSG00000152700 HGNC:10535 SARS gene SARS Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709 28236339;34570399;35790048 False 3 50;50;0 30.556 False ENSG00000031698 ENSG00000031698 HGNC:10537 SARS2 gene SARS2 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis 613845 21255763;24034276;27279129 False 3 100;0;0 30.556 False ENSG00000104835 ENSG00000104835 HGNC:17697 SARS2 gene SARS2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, 613845 PMID: 21255763;24034276 False 3 100;0;0 30.556 True ENSG00000104835 ENSG00000104835 HGNC:17697 SARS2 gene SARS2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, 613845 27604308 False 3 100;0;0 30.556 False ENSG00000104835 ENSG00000104835 HGNC:17697 SATB1 gene SATB1 Expert Review Green;Other Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown intellectual disability;developmental disorders 33057194;33513338 False 3 67;33;0 30.556 False ENSG00000182568 ENSG00000182568 HGNC:10541 SATB2 gene SATB2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Cleft palate and mental retardation, 119540;CLEFT PALATE ISOLATED (CPI) False 3 100;0;0 30.556 False ENSG00000119042 ENSG00000119042 HGNC:21637 SBF1 gene SBF1 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Charcot-Marie-Tooth disease, type 4B3 615284 24799518;23749797;30039846;28902413 False 3 100;0;0 30.556 False ENSG00000100241 ENSG00000100241 HGNC:10542 SC5D gene SC5D Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Lathosterolosis, 607330;LATHOSTEROLOSIS (LATHST) False 3 100;0;0 30.556 False ENSG00000109929 ENSG00000109929 HGNC:10547 SC5D gene SC5D Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Lathosterolosis, 607330;Intellectual disability;Cataracts 27604308;12189593;12812989;30097991 False 3 0;0;0 30.556 False ENSG00000109929 ENSG00000109929 HGNC:10547 SCAF4 gene SCAF4 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Fliedner-Zweier syndrome, OMIM:620511 32730804 False 3 100;0;0 30.556 False ENSG00000156304 ENSG00000156304 HGNC:19304 SCAF4 gene SCAF4 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Fliedner-Zweier syndrome, OMIM:620511 32730804 False 3 100;0;0 30.556 False ENSG00000156304 ENSG00000156304 HGNC:19304 SCAMP5 gene SCAMP5 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Global developmental delay;Intellectual disability;Seizures;Abnormality of nervous system morphology;Behavioral abnormality 31439720;20071347;32020363;33390987 False 3 75;25;0 30.556 False Other ENSG00000198794 ENSG00000198794 HGNC:30386 SCAPER gene SCAPER Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal AUTOSOMAL RECESSIVE MENTAL RETARDATION;Intellectual developmental disorder and retinitis pigmentosa, 618195 21937992;28794130;28041643 False 3 33;0;67 30.556 False ENSG00000140386 ENSG00000140386 HGNC:13081 SCN1A gene SCN1A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Epilepsy, generalized, with febrile seizures plus, type 2, 604403Dravet syndrome, 607208Migraine, familial hemiplegic, 3, 609634Febrile seizures, familial, 3A, 604403;SCN1A-RELATED SEIZURE DISORDERS False 3 100;0;0 30.556 False ENSG00000144285 ENSG00000144285 HGNC:10585 SCN2A gene SCN2A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Seizures, benign familial infantile, 3, 607745Epileptic encephalopathy, early infantile, 11, 613721;NONSPECIFIC SEVERE ID False 3 100;0;0 30.556 False ENSG00000136531 ENSG00000136531 HGNC:10588 SCN3A gene SCN3A Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Epileptic encephalopathy, early infantile, 62, 617938;intellectual disability 29466837 False 3 100;0;0 30.556 False ENSG00000153253 ENSG00000153253 HGNC:10590 SCN8A gene SCN8A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Cognitive impairment with or without cerebellar ataxia, OMIM:614306;Developmental and epileptic encephalopathy 13, OMIM:614558 31625145;24194747;22365152;16236810;25529582;24896178 False 3 100;0;0 30.556 False Other ENSG00000196876 ENSG00000196876 HGNC:10596 SCO1 gene SCO1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 4, OMIM:619048 11013136;19295170;31352446;23878101 False 3 100;0;0 30.556 False ENSG00000133028 ENSG00000133028 HGNC:10603 SCO1 gene SCO1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 4, OMIM:619048 False 3 0;0;0 30.556 False ENSG00000133028 ENSG00000133028 HGNC:10603 SCO1 gene SCO1 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex IV deficiency, nuclear type 4, OMIM:619048 11013136;19295170;31352446;23878101 False 3 100;0;0 30.556 False ENSG00000133028 ENSG00000133028 HGNC:10603 SCO2 gene SCO2 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex IV deficiency;Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, 604377;Myopia 6, 608908;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex IV Deficiency False 3 100;0;0 30.556 False ENSG00000130489 ENSG00000130489 HGNC:10604 SCO2 gene SCO2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex IV Deficiency;Isolated complex IV deficiency;Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors);Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, 604377;Myopia 6, 608908 27604308 False 3 100;0;0 30.556 False ENSG00000130489 ENSG00000130489 HGNC:10604 SCO2 gene SCO2 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, 604377;Myopia 6, 608908;FATAL INFANTILE CARDIOENCEPHALOMYOPATHY DUE TO CYTOCHROME C OXIDASE DEFICIENCY False 3 100;0;0 30.556 False ENSG00000130489 ENSG00000130489 HGNC:10604 SCO2 gene SCO2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 False 3 0;0;0 30.556 False ENSG00000130489 ENSG00000130489 HGNC:10604 SCP2 gene SCP2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukoencephalopathy with dystonia and motor neuropathy False 3 0;0;0 30.556 False ENSG00000116171 ENSG00000116171 HGNC:10606 SCP2 gene SCP2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sterol carrier protein deficiency (Disorders of peroxisomal alpha-, beta and omega-oxidation) 27604308 False 3 0;0;0 30.556 False ENSG00000116171 ENSG00000116171 HGNC:10606 SCYL1 gene SCYL1 Expert Review Green;Literature;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spinocerebellar ataxia, autosomal recessive 21 OMIM:616719;acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome MONDO:0014744 26581903;30914295;29419818;17571074;30531813 False 3 100;0;0 30.556 False ENSG00000142186 ENSG00000142186 HGNC:14372 SDCCAG8 gene SDCCAG8 Victorian Clinical Genetics Services;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Senior-Loken syndrome 7, 613615;Bardet-Biedl syndrome 16, 615993;Intellectual disability 22626039;20835237;22190896;25529582 False 3 100;0;0 30.556 False ENSG00000054282 ENSG00000054282 HGNC:10671 SDHA gene SDHA London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Mitochondrial complex II deficiency, nuclear type 1, OMIM:252011;Neurodegeneration with ataxia and late-onset optic atrophy, OMIM:619259;Cardiomyopathy, dilated, 1GG, OMIM:613642 10976639;27683074;33471299 False 3 100;0;0 30.556 False ENSG00000073578 ENSG00000073578 HGNC:10680 SDHA gene SDHA Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leigh syndrome, 256000Mitochondrial respiratory chain complex II deficiency, 252011Cardiomyopathy, dilated, 1GG, 613642Paragangliomas 5, 614165;LEIGH SYNDROME (NUCLEAR DNA MUTATION) False 3 100;0;0 30.556 False ENSG00000073578 ENSG00000073578 HGNC:10680 SDHA gene SDHA Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial respiratory chain complex II deficiency, OMIM:252011 22972948;24781757 False 3 100;0;0 30.556 False ENSG00000073578 ENSG00000073578 HGNC:10680 SDHA gene SDHA NHS GMS;Expert Review Green;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Mitochondrial complex II deficiency, nuclear type 1, OMIM:252011;Neurodegeneration with ataxia and late-onset optic atrophy, OMIM:619259;Cardiomyopathy, dilated, 1GG, OMIM:613642 10976639;27683074;33471299 False 3 100;0;0 30.556 True ENSG00000073578 ENSG00000073578 HGNC:10680 SDHAF1 gene SDHAF1 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex II deficiency, 252011 19465911;22995659;26642834 False 3 100;0;0 30.556 False ENSG00000205138 ENSG00000205138 HGNC:33867 SDHAF1 gene SDHAF1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MITOCHONDRIAL COMPLEX II DEFICIENCY 0 False 3 33;67;0 30.556 False ENSG00000205138 ENSG00000205138 HGNC:33867 SDHAF1 gene SDHAF1 Expert Review Green;NHS GMS;London North GLH;NHS GMS;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial Diseases;Mitochondrial complex II deficiency, 252011;Complex II (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors);Mitochondrial Respiratory Chain Complex II Deficiency;Isolated complex II deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000205138 ENSG00000205138 HGNC:33867 SDHAF1 gene SDHAF1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex II deficiency 252011 25655951;22995659;19465911 False 3 0;0;0 30.556 False ENSG00000205138 ENSG00000205138 HGNC:33867 SDHB gene SDHB Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex II deficiency, nuclear type 4, OMIM:619224 26642834 - multiple cases reported;25655951;26925370 - suggests incomplete penetrance;22972948 False 3 0;0;0 30.556 False ENSG00000117118 ENSG00000117118 HGNC:10681 SDHB gene SDHB London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex II deficiency, nuclear type 4, OMIM:619224 PMID: 26925370;22972948 False 3 100;0;0 30.556 False ENSG00000117118 ENSG00000117118 HGNC:10681 SDHB gene SDHB Expert Review Green;NHS GMS;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex II deficiency, nuclear type 4, OMIM:619224 22972948;26925370;27604842;32124427 False 3 100;0;0 30.556 True ENSG00000117118 ENSG00000117118 HGNC:10681 SDHD gene SDHD Expert Review Green;NHS GMS;Expert list;Expert;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial respiratory chain complex II deficiency 252011 24367056;26008905 False 3 100;0;0 30.556 True ENSG00000204370 ENSG00000204370 HGNC:10683 SDHD gene SDHD Expert Review Green;NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Complex II (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits);Mitochondrial Diseases;Isolated complex II deficiency 27604308 False 3 100;0;0 30.556 False ENSG00000204370 ENSG00000204370 HGNC:10683 SEC23B gene SEC23B London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dyserythropoietic anemia, congenital, type II, OMIM:224100;COPII component SEC23B (Disorders of multiple glycosylation and other glycosylation pathways, V-ATPase deficiencies) 22208203;35163229 False 3 0;0;0 30.556 False ENSG00000101310 ENSG00000101310 HGNC:10702 SEL1L gene SEL1L Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with hypotonia, poor growth, dysmorphic facies, and agammaglobulinemia, OMIM:621068;?Neurodevelopmental disorder with poor growth, absent speech, progressive ataxia, and dysmorphic facies, OMIM:621067 37943610;37943617 False 3 100;0;0 30.556 False ENSG00000071537 ENSG00000071537 HGNC:10717 SEMA6B gene SEMA6B Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual disability, MONDO:0001071 35604360 False 3 100;0;0 30.556 False ENSG00000167680 ENSG00000167680 HGNC:10739 SEPHS1 gene SEPHS1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Ververi-Brady syndrome 2, OMIM:621325;Neurodevelopmental disorder, MONDO:0700092 38531365 False 3 100;0;0 30.556 False ENSG00000086475 ENSG00000086475 HGNC:19685 SEPSECS gene SEPSECS Expert Review Green;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pontocerebellar hypoplasia type 2D, 613811 26805434;29464431;28133863;26115735;27576344;26888482 False 3 100;0;0 30.556 False ENSG00000109618 ENSG00000109618 HGNC:30605 SERAC1 gene SERAC1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, OMIM:614739;Disorders of mitochondrial membrane lipids (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Multiple respiratory chain complex deficiencies (disorders of protein synthesis) 27604308 False 3 100;0;0 30.556 False ENSG00000122335 ENSG00000122335 HGNC:21061 SERAC1 gene SERAC1 Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, OMIM:614739 29205472;22683713; 16527507;28482397; 28778788; 27186703;27604308 False 3 33;0;67 30.556 False ENSG00000122335 ENSG00000122335 HGNC:21061 SERAC1 gene SERAC1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, OMIM:614739 29205472 False 3 100;0;0 30.556 True ENSG00000122335 ENSG00000122335 HGNC:21061 SET gene SET Expert Review Green;Victorian Clinical Genetics Services;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual disability;SET syndrome;Mental retardation, autosomal dominant 58, 618106 28135719 False 3 67;33;0 30.556 False ENSG00000119335 ENSG00000119335 HGNC:10760 SETBP1 gene SETBP1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual developmental disorder, autosomal dominant 29, OMIM: 616078;Schinzel-Giedion midface retraction syndrome, OMIM: 269150;Schinzel-Giedion syndrome, MONDO:0010010 20436468;21037274;22473152;23020937;25217958;25356899;25028416;25082129;25663181;26096993;26188272;28346496;29463886;32445275;32460883 False 3 100;0;0 30.556 False ENSG00000152217 ENSG00000152217 HGNC:15573 SETD1A gene SETD1A Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with speech impairment and dysmorphic facies, 619056;Epilepsy, early-onset, with or without developmental delay, 618832 28135719;26974950;31197650;32346159 False 3 75;0;25 30.556 False ENSG00000099381 ENSG00000099381 HGNC:29010 SETD1B gene SETD1B Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual developmental disorder with seizures and language delay, OMIM:619000;Intellectual developmental disorder with seizures and language delay, MONDO:0033559 29322246;27106595;25428890;31110234;32546566 False 3 40;60;0 30.556 False ENSG00000139718 ENSG00000139718 HGNC:29187 SETD2 gene SETD2 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Luscan-Lumish syndrome, 616831;intellectual disability 25363768;26084711;24852293;27317772 False 3 100;0;0 30.556 False ENSG00000181555 ENSG00000181555 HGNC:18420 SETD5 gene SETD5 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted MENTAL RETARDATION, AUTOSOMAL DOMINANT 23 24680889;29484850 False 3 100;0;0 30.556 False ENSG00000168137 ENSG00000168137 HGNC:25566 SETX gene SETX Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Spinocerebellar ataxia, autosomal recessive 1, OMIM:606002;Amyotrophic lateral sclerosis 4, juvenile, OMIM:602433 27604308 False 3 100;0;0 30.556 False ENSG00000107290 ENSG00000107290 HGNC:445 SF1 gene SF1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 40987292 False 3 100;0;0 30.556 False ENSG00000168066 ENSG00000168066 HGNC:12950 SFXN4 gene SFXN4 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 18, 615578 24119684 False 3 100;0;0 30.556 False ENSG00000183605 ENSG00000183605 HGNC:16088 SFXN4 gene SFXN4 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 18 615578 31059822;24119684 False 3 100;0;0 30.556 False ENSG00000183605 ENSG00000183605 HGNC:16088 SFXN4 gene SFXN4 Expert Review Green;Expert Review Green;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 18, 615578 24119684 False 3 100;0;0 30.556 False ENSG00000183605 ENSG00000183605 HGNC:16088 SGPL1 gene SGPL1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal "Nephrotic syndrome 14 617575" 28181337; 28165339; 28165343 False 3 100;0;0 30.556 False ENSG00000166224 ENSG00000166224 HGNC:10817 SGSH gene SGSH London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mucopolysaccharidosis Type III;Mucopolysaccharidosis, Type III;Mucopolysaccharidosis Type IIIA;MPS IIIA, Sanfilippo A disease (Mucopolysaccharidoses);MUCOPOLYSACCHARIDOSIS TYPE 3A 27604308 False 3 0;0;0 30.556 False ENSG00000181523 ENSG00000181523 HGNC:10818 SGSH gene SGSH Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MUCOPOLYSACCHARIDOSIS TYPE 3A (MPS3A) 0 False 3 100;0;0 30.556 False ENSG00000181523 ENSG00000181523 HGNC:10818 SHANK1 gene SHANK1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 34113010 False 3 83;0;17 30.556 False ENSG00000161681 ENSG00000161681 HGNC:15474 SHANK2 gene SHANK2 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted SUSCEPTIBILITY TO AUTISM TYPE 17 (AUTS17) 20473310 False 3 100;0;0 30.556 False ENSG00000162105 ENSG00000162105 HGNC:14295 SHANK3 gene SHANK3 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phelan-McDermid syndrome, 606232{Schizophrenia 15}, 613950;PHELAN-MCDERMID SYNDROME False 3 100;0;0 30.556 False ENSG00000251322 ENSG00000251322 HGNC:14294 SHH gene SHH Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Holoprosencephaly-3, 142945Single median maxillary central incisor, 147250Microphthalmia with coloboma 5, 611638Schizencephaly, 269160;TRIPHALANGEAL THUMB-POLYSYNDACTYLY SYNDROME (TPTPS) False 3 100;0;0 30.556 False ENSG00000164690 ENSG00000164690 HGNC:10848 SHMT2 gene SHMT2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities, OMIM:619121 33015733 False 3 100;0;0 30.556 False ENSG00000182199 ENSG00000182199 HGNC:10852 SHMT2 gene SHMT2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities, OMIM:619121 33015733 False 3 100;0;0 30.556 False ENSG00000182199 ENSG00000182199 HGNC:10852 SHOC2 gene SHOC2 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Noonan-like syndrome with loose anagen hair, 607721;NOONAN-LIKE SYNDROME WITH LOOSE ANAGEN HAIR False 3 100;0;0 30.556 False ENSG00000108061 ENSG00000108061 HGNC:15454 SHQ1 gene SHQ1 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Dystonia 35, childhood-onset, OMIM:619921;dystonia 35, childhood-onset, MONDO:0030958;Neurodevelopmental disorder with dystonia and seizures, OMIM:619922;neurodevelopmental disorder with dystonia and seizures, MONDO:0859258 34542157;29178645;36810590;36847845;36416405;37475611;36189577 False 3 50;50;0 30.556 False ENSG00000144736 ENSG00000144736 HGNC:25543 SI gene SI London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal CONGENITAL SUCRASE-ISOMALTASE DEFICIENCY 222900;Disaccharide intolerance 1 (Other carbohydrate disorders) 27604308;14724820;8648527;16329100 False 3 100;0;0 30.556 False ENSG00000090402 ENSG00000090402 HGNC:10856 SIAH1 gene SIAH1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Developmental delay;Infantile hypotonia;Dysmorphic features;Laryngomalacia 32430360 False 3 100;0;0 30.556 False ENSG00000196470 ENSG00000196470 HGNC:10857 SIK1 gene SIK1 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted NEONATAL EPILEPSY SPECTRUM 25839329 False 3 33;67;0 30.556 False ENSG00000142178 ENSG00000142178 HGNC:11142 SIL1 gene SIL1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Marinesco-Sjogren syndrome, 248800;MARINESCO-SJOEGREN SYNDROME (MSS) False 3 100;0;0 30.556 False ENSG00000120725 ENSG00000120725 HGNC:24624 SIN3A gene SIN3A Expert Review Green;Victorian Clinical Genetics Services;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Witteveen-Kolk syndrome, 613406;Syndromic intellectual disability 27399968;28135719;25529582 False 3 100;0;0 30.556 False ENSG00000169375 ENSG00000169375 HGNC:19353 SIN3B gene SIN3B Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Syndromic intellectual disability 33811806 False 3 50;50;0 30.556 False ENSG00000127511 ENSG00000127511 HGNC:19354 SIX3 gene SIX3 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Holoprosencephaly-2, 157170;Schizensephaly, 269160;HOLOPROSENCEPHALY False 3 100;0;0 30.556 False ENSG00000138083 ENSG00000138083 HGNC:10889 SKI gene SKI Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Shprintzen-Goldberg syndrome, 182212;SHPRINTZEN-GOLDBERG CRANIOSYNOSTOSIS SYNDROME; SGS False 3 100;0;0 30.556 False ENSG00000157933 ENSG00000157933 HGNC:10896 SKIV2L gene SKIV2L Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Infantile enterocolitis & monogenic inflammatory bowel disease;Trichohepatoenteric syndrome 2 (Other metabolic disorders) 27604308 False 3 100;0;0 30.556 False ENSG00000204351 ENSG00000204351 HGNC:10898 SLC12A2 gene SLC12A2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Kilquist syndrome;deafness;intellectual disability;dysmorphic features;absent salivation;ectodermal dysplasia;constipation;intestinal malrotation;multiple congenital anomalies 28940097;30740830;32754646;32658972 False 3 100;0;0 30.556 False ENSG00000064651 ENSG00000064651 HGNC:10911 SLC12A3 gene SLC12A3 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Gitelman syndrome, OMIM: 263800;Gitelman syndrome, MONDO:0009904 22009145;27604308;26770037;30999883 False 3 100;0;0 30.556 False ENSG00000070915 ENSG00000070915 HGNC:10912 SLC12A5 gene SLC12A5 NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental and epileptic encephalopathy 34, OMIM;616645 24668262;26333769 False 3 33;0;67 30.556 False ENSG00000124140 ENSG00000124140 HGNC:13818 SLC12A6 gene SLC12A6 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Agenesis of the corpus callosum with peripheral neuropathy, OMIM:218000 12368912;31439721;27485015;16606917;17893295;21628467 False 3 100;0;0 30.556 False ENSG00000140199 ENSG00000140199 HGNC:10914 SLC13A3 gene SLC13A3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate, OMIM:618384 30635937;34966709;35527102;37290914;38235040;33340416 False 3 100;0;0 30.556 False ENSG00000158296 ENSG00000158296 HGNC:14430 SLC13A3 gene SLC13A3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate, OMIM:618384 30635937;34966709;35527102;37290914;38235040;33340416 False 3 100;0;0 30.556 False ENSG00000158296 ENSG00000158296 HGNC:14430 SLC13A3 gene SLC13A3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate, OMIM:618384 30635937;34966709;35527102;37290914;38235040;33340416 False 3 100;0;0 30.556 False ENSG00000158296 ENSG00000158296 HGNC:14430 SLC13A5 gene SLC13A5 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal EPILEPTIC ENCEPHALOPATHY WITH SEIZURE ONSET IN THE FIRST DAYS OF LIFE 24995870 False 3 33;67;0 30.556 False ENSG00000141485 ENSG00000141485 HGNC:23089 SLC16A1 gene SLC16A1 Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Erythrocyte lactate transporter defect, OMIM:245340;Hyperinsulinemic hypoglycemia, familial, 7, OMIM:610021;Monocarboxylate transporter 1 deficiency, OMIM:616095 26608392;17701893 False 3 0;0;0 30.556 False ENSG00000155380 ENSG00000155380 HGNC:10922 SLC16A2 gene SLC16A2 Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Allan-Herndon-Dudley syndrome, OMIM:300523;General Leukodystrophy & Mitochondrial Leukoencephalopathy;Hypomyelinating Leukodystrophy & Pelizaeus-Merzbacher Disease;Monocarboxylate transporter 8 deficiency (MCT8) Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_524 False 3 0;0;0 30.556 False ENSG00000147100 ENSG00000147100 HGNC:10923 SLC16A2 gene SLC16A2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Allan-Herndon-Dudley syndrome, OMIM:300523 False 3 100;0;0 30.556 False ENSG00000147100 ENSG00000147100 HGNC:10923 SLC17A5 gene SLC17A5 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal General Leukodystrophy & Mitochondrial Leukoencephalopathy Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_634 False 3 0;0;0 30.556 False ENSG00000119899 ENSG00000119899 HGNC:10933 SLC17A5 gene SLC17A5 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Salla disease, OMIM:604369;Sialic acid storage disorder, infantile, OMIM:269920 False 3 0;0;0 30.556 False ENSG00000119899 ENSG00000119899 HGNC:10933 SLC17A5 gene SLC17A5 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Salla disease, OMIM:604369;Sialic acid storage disorder, infantile, OMIM:269920 False 3 100;0;0 30.556 False ENSG00000119899 ENSG00000119899 HGNC:10933 SLC18A2 gene SLC18A2 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Brain Dopamine Serotonin Vesicular Transport Disease (Other disorders of neurotransmitter metabolism);Brain Dopamine Serotonin Vesicular Transport Disease (Other disorders of neurotransmitter metabolism) (NO phenotype number in OMIM) 27604308;26497564;23363473 False 3 100;0;0 30.556 False ENSG00000165646 ENSG00000165646 HGNC:10935 SLC19A2 gene SLC19A2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Thiamine-responsive megaloblastic anemia syndrome, OMIM:249270 27604308 False 3 100;0;0 30.556 False ENSG00000117479 ENSG00000117479 HGNC:10938 SLC19A2 gene SLC19A2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Thiamine-responsive megaloblastic anemia syndrome, OMIM:249270 False 3 100;0;0 30.556 True ENSG00000117479 ENSG00000117479 HGNC:10938 SLC19A3 gene SLC19A3 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2),607483 False 3 100;0;0 30.556 True ENSG00000135917 ENSG00000135917 HGNC:16266 SLC19A3 gene SLC19A3 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal THIAMINE METABOLISM DYSFUNCTION SYNDROME 2 (BIOTIN- OR THIAMINE-RESPONSIVE ENCEPHALOPATHY TYPE 2) 15871139;19387023;20065143 False 3 33;67;0 30.556 False ENSG00000135917 ENSG00000135917 HGNC:16266 SLC19A3 gene SLC19A3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Biotin-responsive basal ganglia disease (Disorders of thiamine metabolism);Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2),607483 27604308 False 3 100;0;0 30.556 False ENSG00000135917 ENSG00000135917 HGNC:16266 SLC1A1 gene SLC1A1 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dicarboxylic aminoaciduria 222730 21123949;16311588;894411 False 3 100;0;0 30.556 False ENSG00000106688 ENSG00000106688 HGNC:10939 SLC1A2 gene SLC1A2 Expert Review Green;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Epileptic encephalopathy, early infantile, 41, OMIM:617105;developmental and epileptic encephalopathy, 41, MONDO:0014916 27476654;28777935 False 3 100;0;0 30.556 False ENSG00000110436 ENSG00000110436 HGNC:10940 SLC1A4 gene SLC1A4 Expert Review Green;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, 616657;Intellectual disability 29989513;27193218;26138499;26041762;25930971 False 3 100;0;0 30.556 False ENSG00000115902 ENSG00000115902 HGNC:10942 SLC20A2 gene SLC20A2 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Fahr syndrome;Basal ganglia calcification, idiopathic, 1, 213600;Familial Idiopathic Basal Ganglia Calcification 27245298 - SLC20A2 exon deletions reported in 4 patients with primary brain calcification;26129893;27726124 - Copy number analysis of the WGS data revealed a heterozygous deletion of ~578 kb on chromosome 8. The deletion removes the 5' UTR region, the noncoding exon 1 and the putative promoter region of SLC20A2 as well as the coding regions of six other genes False 3 0;0;0 30.556 False ENSG00000168575 ENSG00000168575 HGNC:10947 SLC22A5 gene SLC22A5 NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Carnitine deficiency, systemic primary, OMIM:212140;systemic primary carnitine deficiency disease, MONDO:0008919 10545605;11261427;27604308;24816252 False 3 100;0;0 30.556 False ENSG00000197375 ENSG00000197375 HGNC:10969 SLC22A5 gene SLC22A5 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Carnitine deficiency, systemic primary, OMIM:212140;systemic primary carnitine deficiency disease, MONDO:0008919 9916797;17884651;25778941;28857146;10545605;11261427 False 3 100;0;0 30.556 False ENSG00000197375 ENSG00000197375 HGNC:10969 SLC25A1 gene SLC25A1 Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of mitochondrial protein transport;Combined D-2- and L-2-hydroxyglutaric aciduria, 615182 23561848 False 3 100;0;0 30.556 False ENSG00000100075 ENSG00000100075 HGNC:10979 SLC25A1 gene SLC25A1 Expert Review Green;London North GLH;NHS GMS;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined D-2- and L-2-hydroxyglutaric aciduria, 615182;Disorders of mitochondrial protein transport;Riboflavin transporter deficiency (Disorders of riboflavin transport and metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000100075 ENSG00000100075 HGNC:10979 SLC25A1 gene SLC25A1 Expert Review Green;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal " Combined D-2- and L-2-hydroxyglutaric aciduria 615182" False 3 100;0;0 30.556 False ENSG00000100075 ENSG00000100075 HGNC:10979 SLC25A12 gene SLC25A12 Expert Review Green;Expert Review Green;London North GLH;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Inherited white matter disorders;Epileptic encephalopathy, early infantile, 39 612949;Hypomyelination, global cerebral, 612949;Disorders of mitochondrial solute import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) 19641205;27290639;24515575 False 3 100;0;0 30.556 False ENSG00000115840 ENSG00000115840 HGNC:10982 SLC25A12 gene SLC25A12 Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epileptic encephalopathy, early infantile, 39,612949;Hypomyelination, global cerebral;Epileptic encephalopathy with global cerebral demyelination;Delayed psychomotor development 27290639;25655951;24515575;19641205;31403263;24515575;19641205;27290639;26633542 False 3 50;50;0 30.556 False ENSG00000115840 ENSG00000115840 HGNC:10982 SLC25A12 gene SLC25A12 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypomyelination, global cerebral False 3 0;0;0 30.556 False ENSG00000115840 ENSG00000115840 HGNC:10982 SLC25A12 gene SLC25A12 Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epileptic encephalopathy, early infantile, 39 612949 24515575;19641205;27290639 False 3 100;0;0 30.556 False ENSG00000115840 ENSG00000115840 HGNC:10982 SLC25A13 gene SLC25A13 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Citrullinemia, adult-onset type II 603471;Citrullinemia, adult-onset type II, 603471Citrullinemia, type II, neonatal-onset, 605814;Citrullinemia Type 2 (Urea cycle disorders and inherited hyperammonaemias) 27604308 False 3 100;0;0 30.556 False ENSG00000004864 ENSG00000004864 HGNC:10983 SLC25A15 gene SLC25A15 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome, OMIM:238970;HHH syndrome (Urea cycle disorders and inherited hyperammonaemias) 27604308 False 3 0;0;0 30.556 False ENSG00000102743 ENSG00000102743 HGNC:10985 SLC25A15 gene SLC25A15 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome, OMIM:238970 False 3 100;0;0 30.556 False ENSG00000102743 ENSG00000102743 HGNC:10985 SLC25A19 gene SLC25A19 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly, Amish type, 607196;Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), 613710 False 3 100;0;0 30.556 True ENSG00000125454 ENSG00000125454 HGNC:14409 SLC25A19 gene SLC25A19 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly, Amish type, 607196;Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), 613710;Microcephaly, Amish type (Disorders of thiamine metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000125454 ENSG00000125454 HGNC:14409 SLC25A20 gene SLC25A20 NHS GMS;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Carnitine-acylcarnitine translocase deficiency 212138;Carnitine acylcarnitine translocase deficiency (Disorders of carnitine transport and the carnitine cycle) 27604308 False 3 0;0;100 30.556 False ENSG00000178537 ENSG00000178537 HGNC:1421 SLC25A20 gene SLC25A20 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Carnitine-acylcarnitine translocase deficiency, OMIM:212138;carnitine-acylcarnitine translocase deficiency, MONDO:0008918 9399886;10384384;10697964;15057979;12859414;24088670;31108048;25778941 False 3 100;0;0 30.556 False ENSG00000178537 ENSG00000178537 HGNC:1421 SLC25A22 gene SLC25A22 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epileptic encephalopathy, early infantile, 3, 609304;EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 3 False 3 100;0;0 30.556 False ENSG00000177542 ENSG00000177542 HGNC:19954 SLC25A22 gene SLC25A22 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epileptic encephalopathy, early infantile, 3, 609304;Disorders of mitochondrial solute import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) 27604308 False 3 50;0;50 30.556 False ENSG00000177542 ENSG00000177542 HGNC:19954 SLC25A24 gene SLC25A24 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Fontaine progeroid syndrome, OMIM:612289;Fontaine progeroid syndrome, MONDO:0012853 29903433;29100093;29100094 False 3 100;0;0 30.556 False ENSG00000085491 ENSG00000085491 HGNC:20662 SLC25A24 gene SLC25A24 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Fontaine progeroid syndrome, OMIM:612289;Fontaine progeroid syndrome, MONDO:0012853 29903433;29100093;29100094 False 3 100;0;0 30.556 False ENSG00000085491 ENSG00000085491 HGNC:20662 SLC25A26 gene SLC25A26 Victorian Clinical Genetics Services;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intra-mitochondrial Methylation Deficiency leading to Clinical findings ranging from neonatal mortality resulting from respiratory insufficiency and hydrops to childhood acute episodes of cardiopulmonary failure and slowly progressive muscle weakness;Combined oxidative phosphorylation deficiency 28;intra-mitochondrial methylation deficiency. PMID: 26522469 False 3 100;0;0 30.556 True ENSG00000144741 ENSG00000144741 HGNC:20661 SLC25A26 gene SLC25A26 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 28;intra-mitochondrial methylation deficiency.;Intra-mitochondrial Methylation Deficiency leading to Clinical findings ranging from neonatal mortality resulting from respiratory insufficiency and hydrops to childhood acute episodes of cardiopulmonary failure and slowly progressive muscle weakness 26522469 False 3 100;0;0 30.556 False ENSG00000144741 ENSG00000144741 HGNC:20661 SLC25A3 gene SLC25A3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial phosphate carrier deficiency, 610773;Mitochondrial phosphate carrier deficiency 610773;Disorders of mitochondrial solute import (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Riboflavin transporter deficiency (Disorders of riboflavin transport and metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000075415 ENSG00000075415 HGNC:10989 SLC25A3 gene SLC25A3 Victorian Clinical Genetics Services;Expert Review Green;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial phosphate carrier deficiency, 610773 27604308;17273968;25681081 False 3 100;0;0 30.556 False ENSG00000075415 ENSG00000075415 HGNC:10989 SLC25A32 gene SLC25A32 Expert list;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Exercise intolerance, riboflavin-responsive 26933868;28443623 False 3 0;0;0 30.556 False ENSG00000164933 ENSG00000164933 HGNC:29683 SLC25A32 gene SLC25A32 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Exercise intolerance, riboflavin-responsive 616839 26933868;28443623 False 3 0;0;0 30.556 False ENSG00000164933 ENSG00000164933 HGNC:29683 SLC25A36 gene SLC25A36 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperinsulinemic hypoglycemia, familial, 8, OMIM:620211 34576089;34971397;36695547 False 3 100;0;0 30.556 False ENSG00000114120 ENSG00000114120 HGNC:25554 SLC25A36 gene SLC25A36 Expert Review Green;Literature;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hyperinsulinemic hypoglycemia, familial, 8, OMIM:620211 34576089;34971397;36695547 False 3 100;0;0 30.556 False ENSG00000114120 ENSG00000114120 HGNC:25554 SLC25A38 gene SLC25A38 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal nonsyndromic autosomal recessive congenital sideroblastic anemia;congenital sideroblastic anemias;severe, non-syndromic, microcytic/hypochromic sideroblastic anemia PMID: 19412178;PMID: 25985931 (mutations detected in 3 patients in this gene);PMID: 21393332 (11 patients);PMID: 19731322 (12 probands with mutations in this gene);PMID: 26821380 (potential novel treatment using glycine and folate). False 3 100;0;0 30.556 True ENSG00000144659 ENSG00000144659 HGNC:26054 SLC25A38 gene SLC25A38 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal severe, non-syndromic, microcytic/hypochromic sideroblastic anemia;Disorders of mitochondrial solute import (Mitochondrial respiratory chain disorders (caused by nuclear variants only));nonsyndromic autosomal recessive congenital sideroblastic anemia;congenital sideroblastic anemias PMID: 26821380 (potential novel treatment using glycine and folate).;PMID: 19731322 (12 probands with mutations in this gene);PMID: 25985931 (mutations detected in 3 patients in this gene);PMID: 21393332 (11 patients);PMID: 19412178 False 3 100;0;0 30.556 False ENSG00000144659 ENSG00000144659 HGNC:26054 SLC25A4 gene SLC25A4 Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Mitochondrial Leukoencephalopathy Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_578;PMID: 27693233 False 3 0;0;0 30.556 False ENSG00000151729 ENSG00000151729 HGNC:10990 SLC25A4 gene SLC25A4 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Progressive External Ophthalmoplegia with Mitochondrial DNADeletions;Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Disorders of mitochondrial DNA maintenance and integrity;Disorders of mitochondrial protein transport;Progressive external ophthalmoplegia with mitochondrial DNA deletions 3, 609283;Mitochondrial DNA depletion syndrome 12 (cardiomyopathic type), 615418 27604308 False 3 100;0;0 30.556 False ENSG00000151729 ENSG00000151729 HGNC:10990 SLC25A4 gene SLC25A4 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;UKGTN;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) 617184;Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) 615418;Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2 609283 False 3 100;0;0 30.556 False ENSG00000151729 ENSG00000151729 HGNC:10990 SLC25A42 gene SLC25A42 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal mitochondrial myopathy;Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression 618416 29923093;29327420;26541337 False 3 100;0;0 30.556 False ENSG00000181035 ENSG00000181035 HGNC:28380 SLC25A42 gene SLC25A42 Expert Review Green;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression 618416;mitochondrial myopathy 26541337;29923093;29327420 False 3 100;0;0 30.556 False ENSG00000181035 ENSG00000181035 HGNC:28380 SLC25A46 gene SLC25A46 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal optic atrophy spectrum disorder 26168012 False 3 100;0;0 30.556 False ENSG00000164209 ENSG00000164209 HGNC:25198 SLC25A46 gene SLC25A46 Victorian Clinical Genetics Services;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal optic atrophy spectrum disorder PMID: 26168012 False 3 100;0;0 30.556 True ENSG00000164209 ENSG00000164209 HGNC:25198 SLC2A1 gene SLC2A1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal GLUT1 deficiency syndrome 1, 606777;GLUT1 deficiency syndrome 2, 612126;{Epilepsy, idiopathic generalized, suscpetibility to, 12}, 614847;Dystonia 9, 601042;GLUT1 DEFICIENCY SYNDROME TYPE 1 (GLUT1DS1) False 3 100;0;0 30.556 False ENSG00000117394 ENSG00000117394 HGNC:11005 SLC2A1 gene SLC2A1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Intellectual disability;Early onset dystonia;Cataracts;Glucose transporter 1 deficiency (blood-brain barrier) (Disorders of glucose transport);Hereditary ataxia;Epileptic encephalopathy;Familial Genetic Generalised Epilepsies;GLUT1 deficiency syndrome 1, infantile onset, severe, 606777;GLUT1 deficiency syndrome 2, childhood onset, 612126 27604308 False 3 0;0;0 30.556 False ENSG00000117394 ENSG00000117394 HGNC:11005 SLC2A2 gene SLC2A2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycogen storage disease type XI (Glycogen storage disorders);Glycogen Storage Disorders- Liver;Glucose transporter 2 deficiency (Disorders of glucose transport);Fanconi-Bickel Syndrome;renal falcon syndrome, aminoaciduria phosphaturia, small stature, malabsorption, hepatomegaly and nephromegaly. 27604308 False 3 0;0;0 30.556 False ENSG00000163581 ENSG00000163581 HGNC:11006 SLC30A10 gene SLC30A10 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypermanganesemia with dystonia 1, OMIM:613280 27604308 False 3 0;0;0 30.556 False ENSG00000196660 ENSG00000196660 HGNC:25355 SLC30A9 gene SLC30A9 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Birk-Landau-Perez syndrome, OMIM:617595 28334855;34716203;37041080 False 3 100;0;0 30.556 False ENSG00000014824 ENSG00000014824 HGNC:1329 SLC32A1 gene SLC32A1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental and epileptic encephalopathy 114, OMIM:620774 36073542 False 3 100;0;0 30.556 False ENSG00000101438 ENSG00000101438 HGNC:11018 SLC33A1 gene SLC33A1 Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital cataracts, hearing loss, and neurodegeneration, 614482 25529582;24896178;22243965 False 3 50;0;50 30.556 False ENSG00000169359 ENSG00000169359 HGNC:95 SLC35A1 gene SLC35A1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIf 603585;Congenital disorder of glycosylation, type Iif, 603585;CMP-sialic acid transporter deficiency (Disorders of multiple glycosylation and other glycosylation pathways) 27604308;23873973;28856833;15576474;30115659 False 3 0;0;100 30.556 False ENSG00000164414 ENSG00000164414 HGNC:11021 SLC35A1 gene SLC35A1 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIf, 603585;intellectual disability, ataxia, seizures, bleeding diathesis and proteinuria 23873973;15576474;28856833;30115659 False 3 33;50;17 30.556 False ENSG00000164414 ENSG00000164414 HGNC:11021 SLC35A2 gene SLC35A2 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Intellectual disability;Congenital disorder of glycosylation, type IIm 300896;SLC35A2-CDG (other congenital disorders of glycosylation) 27743886;25778940;23561849 False 3 100;0;0 30.556 False ENSG00000102100 ENSG00000102100 HGNC:11022 SLC35A2 gene SLC35A2 Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) CONGENITAL DISORDER OF GLYCOSYLATION 0 False 3 33;67;0 30.556 False ENSG00000102100 ENSG00000102100 HGNC:11022 SLC35C1 gene SLC35C1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIc, 266265;CONGENITAL DISORDER OF GLYCOSYLATION TYPE 2C (CDG2C) False 3 100;0;0 30.556 False ENSG00000181830 ENSG00000181830 HGNC:20197 SLC35C1 gene SLC35C1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal GDP-fucose transporter deficiency (Disorders of multiple glycosylation and other glycosylation pathways);Congenital disorder of glycosylation, type IIc 266265 12476046;11326280 False 3 0;0;0 30.556 False ENSG00000181830 ENSG00000181830 HGNC:20197 SLC35D1 gene SLC35D1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 9.2.3. O-xylosyl/N-acetylgalactosaminylglycan synthesis deficiencies (Disorders of protein O-glycosylation) 19508970;17952091 False 3 0;0;0 30.556 False ENSG00000116704 ENSG00000116704 HGNC:20800 SLC37A4 gene SLC37A4 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Glycogen storage disease Ib, OMIM:232220;Glycogen storage disease Ic, OMIM:232240;Congenital disorder of glycosylation, type IIw, OMIM:619525 27604308 False 3 0;0;0 30.556 False ENSG00000137700 ENSG00000137700 HGNC:4061 SLC38A3 gene SLC38A3 Expert Review Green;NHS GMS;Other;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental and epileptic encephalopathy 102, 619881 34605855 False 3 100;0;0 30.556 False ENSG00000188338 ENSG00000188338 HGNC:18044 SLC39A14 gene SLC39A14 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypermanganesemia with dystonia 2 27231142 False 3 100;0;0 30.556 False ENSG00000104635 ENSG00000104635 HGNC:20858 SLC39A14 gene SLC39A14 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal "Hypermanganesemia with dystonia 2 617013" False 3 100;0;0 30.556 False ENSG00000104635 ENSG00000104635 HGNC:20858 SLC39A4 gene SLC39A4 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Acrodermatitis enteropathica (Disorder of zinc metabolism);Acrodermatitis enteropathica 201100 (Disorder of zinc metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000147804 ENSG00000147804 HGNC:17129 SLC39A8 gene SLC39A8 Expert list;London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIn 616721;Hypomagnesaemia with cerebellar atrophy, hypotonia, strabismus, developmental delay, short stature, mild skeletal dysplasia, and connective tissue abnormalities (Disorder of magnesium metabolism) 26637978;26637979 False 3 50;0;50 30.556 False ENSG00000138821 ENSG00000138821 HGNC:20862 SLC39A8 gene SLC39A8 Expert Review Green;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIn 616721 False 3 100;0;0 30.556 False ENSG00000138821 ENSG00000138821 HGNC:20862 SLC3A1 gene SLC3A1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Renal tract calcification (or Nephrolithiasis/nephrocalcinosis);Cystinuria (Disorders of amino acid transport);Hypotonia-cystinuria syndrome (Disorders of amino acid transport) 27604308 False 3 100;0;0 30.556 False ENSG00000138079 ENSG00000138079 HGNC:11025 SLC40A1 gene SLC40A1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Hemochromatosis, type 4 606069 (Disorder of iron metabolism);Hereditary haemochromatosis Type 4 (Disorder of iron metabolism) 27604308;11518736;11431687;10471458 False 3 100;0;0 30.556 False ENSG00000138449 ENSG00000138449 HGNC:10909 SLC46A1 gene SLC46A1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Folate malabsorption, hereditary, OMIM:229050;Hereditary folate malabsorption (Disorders of folate metabolism and transport) 27604308 False 3 0;0;0 30.556 False ENSG00000076351 ENSG00000076351 HGNC:30521 SLC46A1 gene SLC46A1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Folate malabsorption, hereditary, OMIM:229050 17446347;18559978;11804211;11807405;20795774;21333572 False 3 33;67;0 30.556 False ENSG00000076351 ENSG00000076351 HGNC:30521 SLC4A10 gene SLC4A10 Expert Review Green;NHS GMS;Other Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, OMIM:620746 37459438;38054405;31130284 False 3 100;0;0 30.556 False ENSG00000144290 ENSG00000144290 HGNC:13811 SLC4A4 gene SLC4A4 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Renal tubular acidosis, proximal, with ocular abnormalities, 604278;PROXIMAL RENAL TUBULAR ACIDOSIS WITH OCULAR ABNORMALITIES (PRTA-OA) False 3 100;0;0 30.556 False ENSG00000080493 ENSG00000080493 HGNC:11030 SLC52A2 gene SLC52A2 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Brown-Vialetto-Van Laere syndrome 2, OMIM:614707;brown-Vialetto-van Laere syndrome 2, MONDO:0013867 29053833;29193829 False 3 100;0;0 30.556 False ENSG00000185803 ENSG00000185803 HGNC:30224 SLC52A2 gene SLC52A2 NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Brown-Vialetto-Van Laere syndrome 2 614707 False 3 0;0;100 30.556 False ENSG00000185803 ENSG00000185803 HGNC:30224 SLC52A3 gene SLC52A3 NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Brown-Vialetto-Van Laere syndrome 1, OMIM:211530;Brown-Vialetto-van Laere syndrome 1, MONDO:0024537;?Fazio-Londe disease, OMIM:211500;riboflavin transporter deficiency, MONDO:0008891 22718020;29053833;34384672;38469093;40539137 False 3 50;0;50 30.556 False ENSG00000101276 ENSG00000101276 HGNC:16187 SLC52A3 gene SLC52A3 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Brown-Vialetto-Van Laere syndrome 1, OMIM:211530;Brown-Vialetto-van Laere syndrome 1, MONDO:0024537 29053833;29193829 False 3 100;0;0 30.556 False ENSG00000101276 ENSG00000101276 HGNC:16187 SLC5A1 gene SLC5A1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glucose/galactose malabsorption (Disorders of glucose transport);Glucose/galactose malabsorption 606824 (Disorders of glucose transport) 27604308 False 3 100;0;0 30.556 False ENSG00000100170 ENSG00000100170 HGNC:11036 SLC5A6 gene SLC5A6 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodegeneration, infantile-onset, biotin-responsive, OMIM:618973 27904971;31392107;31754459;23104561;29669219 False 3 100;0;0 30.556 False ENSG00000138074 ENSG00000138074 HGNC:11041 SLC5A6 gene SLC5A6 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodegeneration, infantile-onset, biotin-responsive, OMIM:618973 27904971;31392107;31754459;23104561;29669219 False 3 100;0;0 30.556 False ENSG00000138074 ENSG00000138074 HGNC:11041 SLC5A7 gene SLC5A7 Expert Review Green;NHS GMS;Literature;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Myasthenic syndrome, congenital, 20, presynaptic, OMIM:617143 27569547;39135055;36840359;36611016;33250374 False 3 100;0;0 30.556 False ENSG00000115665 ENSG00000115665 HGNC:14025 SLC6A1 gene SLC6A1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Myoclonic-atonic epilepsy, OMIM:616421 25865495;29315614;32469098;34006619;34028503 False 3 100;0;0 30.556 False ENSG00000157103 ENSG00000157103 HGNC:11042 SLC6A17 gene SLC6A17 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MENTAL RETARDATION, AUTOSOMAL RECESSIVE 48 25704603 False 3 100;0;0 30.556 False ENSG00000197106 ENSG00000197106 HGNC:31399 SLC6A19 gene SLC6A19 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hartnup disorder, OMIM:234500 27604308;20399395;19335424;19033659 False 3 100;0;0 30.556 False ENSG00000174358 ENSG00000174358 HGNC:27960 SLC6A19 gene SLC6A19 Expert Review Green;Literature;Expert Review;UKGTN;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal " Hartnup disorder 234500; Iminoglycinuria, digenic 242600" 27604308 20399395; 19335424 False 3 100;0;0 30.556 False ENSG00000174358 ENSG00000174358 HGNC:27960 SLC6A3 gene SLC6A3 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal PARKINSONISM-DYSTONIA, INFANTILE 0 False 3 33;67;0 30.556 False ENSG00000142319 ENSG00000142319 HGNC:11049 SLC6A3 gene SLC6A3 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;Early onset dystonia;Dopamine transporter deficiency syndrome (Other disorders of neurotransmitter metabolism);Parkinson Disease and Complex Parkinsonism 27604308 False 3 100;0;0 30.556 False ENSG00000142319 ENSG00000142319 HGNC:11049 SLC6A8 gene SLC6A8 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Intellectual disability;Creatine transporter deficiency (Mitochondrial respiratory chain disorders (caused by nuclear variants only), disorders of creatinine metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000130821 ENSG00000130821 HGNC:11055 SLC6A8 gene SLC6A8 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Cerebral creatine deficiency syndrome 1, 300352;X-LINKED CREATINE DEFICIENCY SYNDROME (XL-CDS) False 3 100;0;0 30.556 False ENSG00000130821 ENSG00000130821 HGNC:11055 SLC6A9 gene SLC6A9 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Glycine encephalopathy with normal serum glycine, OMIM:617301 27481395;27773429 False 3 50;50;0 30.556 False ENSG00000196517 ENSG00000196517 HGNC:11056 SLC7A7 gene SLC7A7 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Lysinuric protein intolerance (Disorders of amino acid transport);Lysinuric protein intolerance 222700 27604308 False 3 0;0;0 30.556 False ENSG00000155465 ENSG00000155465 HGNC:11065 SLC7A9 gene SLC7A9 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Renal tract calcification (or Nephrolithiasis/nephrocalcinosis);Cystinuria (Disorders of amino acid transport) 27604308;24816252;12239244 False 3 100;0;0 30.556 False ENSG00000021488 ENSG00000021488 HGNC:11067 SLC9A6 gene SLC9A6 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory;UKGTN Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Mental retardation, X-linked syndromic, Christianson type, 300243;MENTAL RETARDATION SYNDROMIC X-LINKED CHRISTIANSON TYPE (MRXSC) 18342287;25044251;20395263;10528855;18342287;25529582;24896178;27256868 False 3 100;0;0 30.556 False ENSG00000198689 ENSG00000198689 HGNC:11079 SLX4 gene SLX4 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal FANCONI ANEMIA COMPLEMENTATION GROUP P 21240275;21240277 False 3 33;67;0 30.556 False ENSG00000188827 ENSG00000188827 HGNC:23845 SMAD4 gene SMAD4 Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Myhre syndrome, 139210;Includes intellectual disability 22243968;22585601;25529582;24896178 False 3 50;0;50 30.556 False ENSG00000141646 ENSG00000141646 HGNC:6770 SMARCA1 gene SMARCA1 Expert Review Green;NHS GMS;Other Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) X-linked intellectual disability, MONDO:0100284 26539891;26740508;27479843;27457812;33057194;40316778 False 3 67;0;33 30.556 False ENSG00000102038 ENSG00000102038 HGNC:11097 SMARCA2 gene SMARCA2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Nicolaides-Baraitser syndrome, OMIM:601358;Coffin-siris syndrome;Blepharophimosis intellectual disability syndrome 22822383;22366787;32694869 False 3 100;0;0 30.556 False ENSG00000080503 ENSG00000080503 HGNC:11098 SMARCA4 gene SMARCA4 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Coffin-Siris syndrome 4, OMIM:614609 False 3 100;0;0 30.556 False ENSG00000127616 ENSG00000127616 HGNC:11100 SMARCA5 gene SMARCA5 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted intellectual disability;postnatal microcephaly;hypotonia;failure to thrive 33980485 False 3 100;0;0 30.556 False ENSG00000153147 ENSG00000153147 HGNC:11101 SMARCB1 gene SMARCB1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Coffin-Siris syndrome 3, OMIM:614608 False 3 100;0;0 30.556 False ENSG00000099956 ENSG00000099956 HGNC:11103 SMARCC2 gene SMARCC2 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Global developmental delay;Intellectual disability;neurodevelopmental delay and growth retardation;prominent speech impairment, hypotonia, feeding difficulties, behavioral abnormalities, and dysmorphic features 26350204;27392482;30580808 False 3 25;0;75 30.556 False ENSG00000139613 ENSG00000139613 HGNC:11105 SMARCD1 gene SMARCD1 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Generalized hypotonia;Feeding difficulties;Global developmental delay;Intellectual disability;Abnormality of the hand;Abnormality of the foot;Coffin-Siris syndrome 11, 618779 26350204;30879640 False 3 40;0;60 30.556 False ENSG00000066117 ENSG00000066117 HGNC:11106 SMARCE1 gene SMARCE1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Coffin-Siris syndrome 5, OMIM:616938 22426308 False 3 100;0;0 30.556 False ENSG00000073584 ENSG00000073584 HGNC:11109 SMC1A gene SMC1A Victorian Clinical Genetics Services;Expert Review Green;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Cornelia de Lange syndrome 2, OMIM:300590;Cornelia de Lange syndrome 2, MONDO:0010370;Developmental and epileptic encephalopathy 85, with or without midline brain defects, OMIM:301044;Developmental and epileptic encephalopathy, 85, with or without midline brain defects, MONDO:0026771 False 3 100;0;0 30.556 False ENSG00000072501 ENSG00000072501 HGNC:11111 SMC3 gene SMC3 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Cornelia de Lange syndrome 3, 610759;CDLS3 17273969;25655089;25125236;25529582 False 3 50;0;50 30.556 False ENSG00000108055 ENSG00000108055 HGNC:2468 SMG8 gene SMG8 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;Microcephaly;Short stature;Facial dysmorphism 31130284;33242396 False 3 100;0;0 30.556 False ENSG00000167447 ENSG00000167447 HGNC:25551 SMOC1 gene SMOC1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microphthalmia with limb anomalies, 206920;OPHTHALMOACROMELIC SYNDROME (OAS) False 3 100;0;0 30.556 False ENSG00000198732 ENSG00000198732 HGNC:20318 SMPD1 gene SMPD1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Niemann-Pick disease, type A, 257200Niemann-Pick disease, type B, 607616;NIEMANN-PICK DISEASE TYPE A (NPDA) False 3 100;0;0 30.556 False ENSG00000166311 ENSG00000166311 HGNC:11120 SMPD1 gene SMPD1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Niemann-Pick disease, type A, 257200;Niemann-Pick disease, type B, 607616 27604308 False 3 0;0;0 30.556 False ENSG00000166311 ENSG00000166311 HGNC:11120 SMPD4 gene SMPD4 Expert Review Green;Research Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal cerebellar hypoplasia, hypomyelination, microcephaly, arthrogryposis 31495489 False 3 0;100;0 30.556 False ENSG00000136699 ENSG00000136699 HGNC:32949 SMS gene SMS Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked, Snyder-Robinson type, 309583;SNYDER-ROBINSON SYNDROME (SRS) False 3 100;0;0 30.556 False ENSG00000102172 ENSG00000102172 HGNC:11123 SNAP25 gene SNAP25 Expert Review Green;Expert Review Green;Literature;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown ?Myasthenic syndrome, congenital 18, 616330;?Myasthenic syndrome, congenital, 18, 616330 29100083;28135719;25003006;29491473;25381298;30914295 False 3 100;0;0 30.556 False ENSG00000132639 ENSG00000132639 HGNC:11132 SNAP29 gene SNAP29 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome, 609528;CEDNIK SYNDROME False 3 100;0;0 30.556 False ENSG00000099940 ENSG00000099940 HGNC:11133 SNF8 gene SNF8 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 38423010 False 3 100;0;0 30.556 False ENSG00000159210 ENSG00000159210 HGNC:17028 SNIP1 gene SNIP1 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Psychomotor retardation, epilepsy, and craniofacial dysmorphism OMIM:614501;psychomotor retardation, epilepsy, and craniofacial dysmorphism MONDO:0013787 22279524;34570759 False 3 0;0;100 30.556 False ENSG00000163877 ENSG00000163877 HGNC:30587 SNORD118 gene SNORD118 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukoencephalopathy, brain calcifications, and cysts, OMIM:614561 28177126;27571260;33029936 False 3 100;0;0 30.556 False Other - please provide details in the comments ENSG00000200463 ENSG00000200463 HGNC:32952 SNORD118 gene SNORD118 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukoencephalopathy, brain calcifications, and cysts 614561 False 3 80;20;0 30.556 False ENSG00000200463 ENSG00000200463 HGNC:32952 SNRPB gene SNRPB Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted CEREBRO-COSTO-MANDIBULAR SYNDROME 0 False 3 33;67;0 30.556 False ENSG00000125835 ENSG00000125835 HGNC:11153 SNX14 gene SNX14 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ID, MACROCEPHALY AND CEREBELLAR HYPOPLASIA 0 False 3 60;40;0 30.556 False ENSG00000135317 ENSG00000135317 HGNC:14977 SNX27 gene SNX27 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Generalized hypotonia;Global developmental delay;Intellectual disability;Seizures 25894286;31721175;21300787;23524343 False 3 100;0;0 30.556 False ENSG00000143376 ENSG00000143376 HGNC:20073 SOD1 gene SOD1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic tetraplegia and axial hypotonia, progressive, OMIM:618598 31314961;31332433;34380534;34788402;36935613;39629626 False 3 100;0;0 30.556 False ENSG00000142168 ENSG00000142168 HGNC:11179 SON gene SON Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown "ZTTK syndrome 617140" False 3 100;0;0 30.556 False ENSG00000159140 ENSG00000159140 HGNC:11183 SOS1 gene SOS1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Fibromatosis, gingival, 135300Noonan syndrome 4, 610733;NOONAN SYNDROME 4 False 3 100;0;0 30.556 False ENSG00000115904 ENSG00000115904 HGNC:11187 SOS2 gene SOS2 Expert Review Green;Other Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Noonan syndrome 9 25795793;26173643 False 3 0;0;0 30.556 False ENSG00000100485 ENSG00000100485 HGNC:11188 SOX10 gene SOX10 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Waardenburg syndrome, type 4C, 613266Waardenburg syndrome, type 2E, with or without neurologic involvement, 611584PCWH syndrome, 609136;PERIPHERAL DEMYELINATING NEUROPATHY, CENTRAL DYSMYELINATING LEUKODYSTROPHY, WAARDENBURG SYNDROME, AND HIRSCHSPRUNG DISEASE (PCWH) False 3 100;0;0 30.556 False ENSG00000100146 ENSG00000100146 HGNC:11190 SOX10 gene SOX10 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown General Leukodystrophy & Mitochondrial Leukoencephalopathy;PERIPHERAL DEMYELINATING NEUROPATHY, CENTRAL DYSMYELINATING LEUKODYSTROPHY, WAARDENBURG SYNDROME, AND HIRSCHSPRUNG DISEASE;peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy 25655951 False 3 0;0;0 30.556 False ENSG00000100146 ENSG00000100146 HGNC:11190 SOX11 gene SOX11 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Coffin-Siris syndrome 9, OMIM:615866 24886874;26543203 False 3 100;0;0 30.556 False ENSG00000176887 ENSG00000176887 HGNC:11191 SOX2 gene SOX2 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted AEG SYNDROME 0 False 3 33;67;0 30.556 False ENSG00000181449 ENSG00000181449 HGNC:11195 SOX4 gene SOX4 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Coffin-Siris syndrome 10, OMIM:618506;Syndromic intellectual disability;Global developmental delay;Intellectual disability;Growth delay;Clinodactyly of the 5th finger;facial dysmorphism 30661772;35232796 False 3 100;0;0 30.556 False ENSG00000124766 ENSG00000124766 HGNC:11200 SOX5 gene SOX5 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted 12P12.5 INTRAGENIC DELETIONS ASSOCIATED WITH INTELLECTUAL DISABILITY 22290657 False 3 100;0;0 30.556 False ENSG00000134532 ENSG00000134532 HGNC:11201 SOX6 gene SOX6 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted intellectual diability;ADHD;Craniosynostosis;Osteochondromas 32442410 False 3 100;0;0 30.556 False ENSG00000110693 ENSG00000110693 HGNC:16421 SPART gene SPART Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Troyer syndrome, OMIM:275900 18413476; 20437587; 26003402; 28679690 False 3 100;0;0 30.556 False ENSG00000133104 ENSG00000133104 HGNC:18514 SPART gene SPART Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Troyer syndrome, OMIM:275900 27112432;18413476;26003402;12134148;28875386;15372254;31535723 False 3 100;0;0 30.556 False ENSG00000133104 ENSG00000133104 HGNC:18514 SPAST gene SPAST Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Spastic paraplegia 4, autosomal dominant, OMIM:182601;hereditary spastic paraplegia 4, MONDO:0008438 39731306;39457434 False 3 75;0;25 30.556 False ENSG00000021574 ENSG00000021574 HGNC:11233 SPATA5 gene SPATA5 Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, OMIM:616577 26299366;29343804;25529582 False 3 100;0;0 30.556 False ENSG00000145375 ENSG00000145375 HGNC:18119 SPATA5 gene SPATA5 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, OMIM:616577 27246907;29343804;26299366;28293831;30009132;36849973 False 3 100;0;0 30.556 False ENSG00000145375 ENSG00000145375 HGNC:18119 SPATA5 gene SPATA5 Expert Review Green;Literature;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, OMIM:616577 27246907;29343804;26299366;28293831;30009132;36849973 False 3 100;0;0 30.556 False ENSG00000145375 ENSG00000145375 HGNC:18119 SPATA5L1 gene SPATA5L1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with hearing loss and spasticity, OMIM:619616 34626583 False 3 100;0;0 30.556 False ENSG00000171763 ENSG00000171763 HGNC:28762 SPECC1L gene SPECC1L Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Opitz GBBB syndrome, type II,145410;Intellectual disability;Autosomal dominant Opitz G/BBB syndrome 1897571;8849002;25412741 False 3 50;50;0 30.556 False ENSG00000100014 ENSG00000100014 HGNC:29022 SPEN gene SPEN Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental disorders 33057194;33596411 False 3 100;0;0 30.556 False ENSG00000065526 ENSG00000065526 HGNC:17575 SPG11 gene SPG11 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 11, autosomal recessive, 604360;SPASTIC PARAPLEGIA-11 False 3 100;0;0 30.556 False ENSG00000104133 ENSG00000104133 HGNC:11226 SPG11 gene SPG11 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paralplegia 11, autosomal recessive, OMIM:604360 14745065;18067136;33581793 False 3 100;0;0 30.556 False ENSG00000104133 ENSG00000104133 HGNC:11226 SPG7 gene SPG7 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Spastic paraplegia 7, autosomal recessive, OMIM:607259;hereditary spastic paraplegia 7, MONDO:0011803 27604308;9635427;16534102;17646629;18200586;20186691;22571692;30252181;33045469;39978794 False 3 100;0;0 30.556 False ENSG00000197912 ENSG00000197912 HGNC:11237 SPG7 gene SPG7 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Spastic paraplegia 7, autosomal recessive, OMIM:607259;hereditary spastic paraplegia 7, MONDO:0011803 9635427;16534102;17646629;18200586;20186691;22571692 False 3 100;0;0 30.556 True ENSG00000197912 ENSG00000197912 HGNC:11237 SPOP gene SPOP Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Nabais Sa-de Vries syndrome, type 1, 618828;Nabais Sa-de Vries syndrome, type 2, 618829 32109420 False 3 100;0;0 30.556 False Other ENSG00000121067 ENSG00000121067 HGNC:11254 SPOUT1 gene SPOUT1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with poor growth, seizures, and brain abnormalities, OMIM:621154 39962046 False 3 100;0;0 30.556 False ENSG00000198917 ENSG00000198917 HGNC:26933 SPR gene SPR Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716 11443547 False 3 33;67;0 30.556 False ENSG00000116096 ENSG00000116096 HGNC:11257 SPR gene SPR Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716;Sepiapterin reductase deficiency (Disorders of pterin metabolism) 27604308;22018912;22522443;22018912;24588500;28189489;21431957;16650784 False 3 100;0;0 30.556 False ENSG00000116096 ENSG00000116096 HGNC:11257 SPRED1 gene SPRED1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Legius syndrome, 611431;LEGIUS SYNDROME False 3 100;0;0 30.556 False ENSG00000166068 ENSG00000166068 HGNC:20249 SPRED2 gene SPRED2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal developmental delay;intellectual disability;cardiac defects;short stature;skeletal anomalies;a typical facial gestalt 34626534 False 3 100;0;0 30.556 False ENSG00000198369 ENSG00000198369 HGNC:17722 SPTAN1 gene SPTAN1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental and epileptic encephalopathy 5, OMIM:613477;Developmental delay with or without epilepsy, OMIM:620540;Spastic paraplegia 91, autosomal dominant, with or without cerebellar ataxia, OMIM:620538 36331550;20493457;22258530;24896178 False 3 100;0;0 30.556 False ENSG00000197694 ENSG00000197694 HGNC:11273 SPTBN1 gene SPTBN1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown autosomal dominant neurodevelopmental syndrome 34211179 False 3 100;0;0 30.556 False ENSG00000115306 ENSG00000115306 HGNC:11275 SPTBN2 gene SPTBN2 Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spinocerebellar ataxia, autosomal recessive 14, OMIM:615386 23236289; 23838597; 28636205 False 3 100;0;0 30.556 False ENSG00000173898 ENSG00000173898 HGNC:11276 SPTBN4 gene SPTBN4 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519 28540413;28940097;29861105;31230720;31857255 False 3 100;0;0 30.556 False ENSG00000160460 ENSG00000160460 HGNC:14896 SPTLC1 gene SPTLC1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Charcot-Marie-Tooth disease;Serine palmitoyl transferase deficiency (Disorders of complex lipid synthesis);Familial dysautonomia 27604308;21618344;20097765;30420926 False 3 100;0;0 30.556 False ENSG00000090054 ENSG00000090054 HGNC:11277 SPTLC2 gene SPTLC2 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Charcot-Marie-Tooth disease;Serine palmitoyl transferase deficiency (Disorders of complex lipid synthesis);Familial dysautonomia 27604308;20920666 False 3 100;0;0 30.556 False ENSG00000100596 ENSG00000100596 HGNC:11278 SQOR gene SQOR Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sulfide:quinone oxidoreductase deficiency, OMIM:619221 32160317 False 3 75;25;0 30.556 False ENSG00000137767 ENSG00000137767 HGNC:20390 SQOR gene SQOR Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sulfide:quinone oxidoreductase deficiency, OMIM:619221 32160317 False 3 67;33;0 30.556 False ENSG00000137767 ENSG00000137767 HGNC:20390 SRCAP gene SRCAP Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, OMIM:619595;Floating-Harbor syndrome, OMIM:136140 33909990;20358590;22265015 False 3 100;0;0 30.556 False ENSG00000080603 ENSG00000080603 HGNC:16974 SRD5A3 gene SRD5A3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal SRD5A3-CDG (Disorders of protein N-glycosylation);Congenital disorder of glycosylation, type Iq 612379 27604308 False 3 0;0;0 30.556 False ENSG00000128039 ENSG00000128039 HGNC:25812 SRD5A3 gene SRD5A3 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Iq, 612379Kahrizi syndrome, 612713;CONGENITAL DISORDERS OF GLYCOSYLATION False 3 100;0;0 30.556 False ENSG00000128039 ENSG00000128039 HGNC:25812 SRPK3 gene SRPK3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Intellectual developmental disorder, X-linked 114, OMIM:301134 39073169 False 3 100;0;0 30.556 False ENSG00000184343 ENSG00000184343 HGNC:11402 SRRM2 gene SRRM2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual developmental disorder, autosomal dominant 72, OMIM:620439 35567594;33057194 False 3 60;40;0 30.556 False ENSG00000167978 ENSG00000167978 HGNC:16639 SRSF1 gene SRSF1 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, OMIM:620489 37071997 False 3 100;0;0 30.556 False ENSG00000136450 ENSG00000136450 HGNC:10780 SSBP1 gene SSBP1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Optic atrophy 13 with retinal and foveal abnormalities, OMIM:165510 29182774;34905022;31298765;31479473;31550237;31550240 False 3 100;0;0 30.556 False ENSG00000106028 ENSG00000106028 HGNC:11317 SSBP1 gene SSBP1 NHS GMS;Expert list;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Optic atrophy 13 with retinal and foveal abnormalities, OMIM:165510 31298765;31550240;31550237;30412255;31479473;34905022 False 3 0;0;0 30.556 False ENSG00000106028 ENSG00000106028 HGNC:11317 SSR4 gene SSR4 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Congenital disorder of glycosylation, type Iy, 300934;CDG syndrome type Iy;SSR4-CDG 26264460;24218363 False 3 100;0;0 30.556 False ENSG00000180879 ENSG00000180879 HGNC:11326 SSR4 gene SSR4 Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Congenital disorder of glycosylation, type Iy 300934 26264460 False 3 0;0;0 30.556 False ENSG00000180879 ENSG00000180879 HGNC:11326 ST3GAL3 gene ST3GAL3 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental and epileptic encephalopathy 15, OMIM:615006;developmental and epileptic encephalopathy, 15, MONDO:0014003;Intellectual developmental disorder, autosomal recessive 12, OMIM:611090;intellectual disability, autosomal recessive 12, MONDO:0012612 27604308;21907012;23252400;31584066;17120046;25529582 False 3 100;0;0 30.556 False ENSG00000126091 ENSG00000126091 HGNC:10866 ST3GAL3 gene ST3GAL3 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental and epileptic encephalopathy 15, OMIM:615006;developmental and epileptic encephalopathy, 15, MONDO:0014003;Intellectual developmental disorder, autosomal recessive 12, OMIM:611090;intellectual disability, autosomal recessive 12, MONDO:0012612 27604308;21907012;23252400;31584066;17120046;25529582 False 3 100;0;0 30.556 False ENSG00000126091 ENSG00000126091 HGNC:10866 ST3GAL5 gene ST3GAL5 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Lactosylceramide alpha-2,3-sialyltransferase deficiency (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation);Salt and pepper developmental regression syndrome 609056;GM3 synthase deficiency (Disorders of complex lipid synthesis) 24026681;15502825 False 3 0;0;0 30.556 False ENSG00000115525 ENSG00000115525 HGNC:10872 ST3GAL5 gene ST3GAL5 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Salt and pepper developmental regression syndrome, 609056;Developmental regression;Intellectual disability 24026681;27232954;26649472;25529582 False 3 50;50;0 30.556 False ENSG00000115525 ENSG00000115525 HGNC:10872 STAG1 gene STAG1 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Mental retardation, autosomal dominant 47, 617635;Syndromic unspecific intellectual disability 28119487;26350204;25529582 False 3 50;0;50 30.556 False ENSG00000118007 ENSG00000118007 HGNC:11354 STAG2 gene STAG2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) STAG2-related developmental delay with microcephaly and congenital anomalies;STAG2-related X-linked Intellectual Deficiency;cohesinopathy;Global developmental delay;Intellectual disability;Abnormality of head or neck;Microcephaly;Growth delay;Hearing impairment;Abnormal heart morphology 29263825;28296084;30158690;30447054;19449417;26443594;25677961;23637084;25450604 False 3 100;0;0 30.556 False ENSG00000101972 ENSG00000101972 HGNC:11355 STAMBP gene STAMBP Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly-capillary malformation syndrome, OMIM:614261 23542699 False 3 33;67;0 30.556 False ENSG00000124356 ENSG00000124356 HGNC:16950 STIL gene STIL Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly 7, primary, autosomal recessive, 612703;MICROCEPHALY PRIMARY TYPE 7 False 3 100;0;0 30.556 False ENSG00000123473 ENSG00000123473 HGNC:10879 STN1 gene STN1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cerebroretinal microangiopathy with calcifications and cysts 2, OMIM:617341 27432940;32627942 False 3 100;0;0 30.556 False ENSG00000107960 ENSG00000107960 HGNC:26200 STRA6 gene STRA6 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microphthalmia, syndromic 9, 601186Microphthalmia, isolated, with coloboma 8, 601186;MICROPHTHALMIA SYNDROMIC TYPE 9 (MCOPS9) False 3 100;0;0 30.556 False ENSG00000137868 ENSG00000137868 HGNC:30650 STRADA gene STRADA Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Polyhydramnios, megalencephaly, and symptomatic epilepsy, MIM:611087 (includes mental retardation); severe psychomotor retardation 27170158;17522105;28688840 False 3 50;50;0 30.556 False ENSG00000266173 ENSG00000266173 HGNC:30172 STS gene STS Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) X-linked ichthyosis (Other disorders in the metabolism of sterols);Autosomal recessive congenital ichthyosis 27604308;1539590;29672931 False 3 100;0;0 30.556 False ENSG00000101846 ENSG00000101846 HGNC:11425 STT3A gene STT3A Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Iw, autosomal dominant, OMIM:619714;Congenital disorder of glycosylation, type Iw, autosomal recessive, OMIM:615596 23842455;28424003;30701557;34653363 False 3 100;0;0 30.556 False ENSG00000134910 ENSG00000134910 HGNC:6172 STT3A gene STT3A NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Congenital disorder of glycosylation, type Iw, autosomal dominant, OMIM:619714;Congenital disorder of glycosylation, type Iw, autosomal recessive, OMIM:615596 23842455;28424003;30701557;34653363 False 3 50;0;50 30.556 False ENSG00000134910 ENSG00000134910 HGNC:6172 STX1A gene STX1A Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 36564538 False 3 100;0;0 30.556 False ENSG00000106089 ENSG00000106089 HGNC:11433 STX1B gene STX1B Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted GENERALIZED EPILEPSY WITH FEBRILE SEIZURES PLUS, TYPE 9 25362483 False 3 33;67;0 30.556 False ENSG00000099365 ENSG00000099365 HGNC:18539 STXBP1 gene STXBP1 NHS GMS;Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Developmental and epileptic encephalopathy 4, OMIM:612164;developmental and epileptic encephalopathy, 4, MONDO:0012812 35190816;31855252;18469812;19557857 False 3 100;0;0 30.556 False ENSG00000136854 ENSG00000136854 HGNC:11444 SUCLA2 gene SUCLA2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073;Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Disorders of mitochondrial DNA maintenance and integrity 27604308 False 3 100;0;0 30.556 False ENSG00000136143 ENSG00000136143 HGNC:11448 SUCLA2 gene SUCLA2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073 Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_575 False 3 0;0;0 30.556 False ENSG00000136143 ENSG00000136143 HGNC:11448 SUCLA2 gene SUCLA2 Victorian Clinical Genetics Services;UKGTN;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073;Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Disorders of mitochondrial DNA maintenance and integrity False 3 100;0;0 30.556 False ENSG00000136143 ENSG00000136143 HGNC:11448 SUCLG1 gene SUCLG1 Victorian Clinical Genetics Services;UKGTN;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of mitochondrial DNA maintenance and integrity;Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria),245400;Mitochondrial DNA Depletion Syndrome False 3 100;0;0 30.556 False ENSG00000163541 ENSG00000163541 HGNC:11449 SUCLG1 gene SUCLG1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal FATAL INFANTILE LACTIC ACIDOSIS 0 False 3 33;67;0 30.556 False ENSG00000163541 ENSG00000163541 HGNC:11449 SUCLG1 gene SUCLG1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Mitochondrial DNA Depletion Syndrome;Disorders of mitochondrial DNA maintenance and integrity;Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria),245400 27604308 False 3 100;0;0 30.556 False ENSG00000163541 ENSG00000163541 HGNC:11449 SUFU gene SUFU Expert Review Green;NHS GMS;Literature;Literature Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Joubert syndrome 32, OMIM:617757 21289193;28965847;33024317;34675124 False 3 100;0;0 30.556 False ENSG00000107882 ENSG00000107882 HGNC:16466 SUMF1 gene SUMF1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple sulfatase deficiency 27604308 False 3 0;0;0 30.556 False ENSG00000144455 ENSG00000144455 HGNC:20376 SUMF1 gene SUMF1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal SULFATIDOSIS, JUVENILE, AUSTIN TYPE 12757706;21224894;12757705 False 3 33;67;0 30.556 False ENSG00000144455 ENSG00000144455 HGNC:20376 SUMF1 gene SUMF1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal General Leukodystrophy & Mitochondrial Leukoencephalopathy;Multiple sulfatase deficiency Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_628 False 3 0;0;0 30.556 False ENSG00000144455 ENSG00000144455 HGNC:20376 SUOX gene SUOX London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sulfite oxidase deficiency 27604308;27289259;12112661 False 3 0;0;0 30.556 False ENSG00000139531 ENSG00000139531 HGNC:11460 SUOX gene SUOX Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sulfite oxidase deficiency, 272300 27604308; 27289259; 12112661 False 3 0;0;100 30.556 False ENSG00000139531 ENSG00000139531 HGNC:11460 SUPT16H gene SUPT16H Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480;Global developmental delay;Intellectual disability;Abnormality of the corpus callosum 31924697;36226587;36255738 False 3 0;100;0 30.556 False ENSG00000092201 ENSG00000092201 HGNC:11465 SUPV3L1 gene SUPV3L1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial RNA Helicase SUPV3L1-Associated neurodegenerative syndrome 35023579;39596606 False 3 100;0;0 30.556 False ENSG00000156502 ENSG00000156502 HGNC:11471 SUPV3L1 gene SUPV3L1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial RNA Helicase SUPV3L1-Associated neurodegenerative syndrome 35023579;39596606 False 3 100;0;0 30.556 False ENSG00000156502 ENSG00000156502 HGNC:11471 SUPV3L1 gene SUPV3L1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial RNA Helicase SUPV3L1-Associated neurodegenerative syndrome 35023579;39596606 False 3 100;0;0 30.556 False ENSG00000156502 ENSG00000156502 HGNC:11471 SURF1 gene SURF1 Victorian Clinical Genetics Services;Expert Review Green;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex IV deficiency;Leigh syndrome, due to COX deficiency, 256000;Mitochondrial Diseases;Leigh Syndrome;Complex IV deficiency False 3 100;0;0 30.556 True ENSG00000148290 ENSG00000148290 HGNC:11474 SURF1 gene SURF1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial Diseases;Complex IV deficiency;Leigh Syndrome;Isolated complex IV deficiency;Leigh syndrome, due to COX deficiency, 256000;Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors) 27604308 False 3 100;0;0 30.556 False ENSG00000148290 ENSG00000148290 HGNC:11474 SURF1 gene SURF1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leigh syndrome, due to COX IV deficiency;Mitochondrial Leukoencephalopathy;Mitochondrial complex IV disorder Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_560 False 3 0;0;0 30.556 False ENSG00000148290 ENSG00000148290 HGNC:11474 SURF1 gene SURF1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leigh syndrome, due to COX deficiency, 256000;LEIGH SYNDROME (NUCLEAR DNA MUTATION) False 3 100;0;0 30.556 False ENSG00000148290 ENSG00000148290 HGNC:11474 SUZ12 gene SUZ12 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Imagawa-Matsumoto syndrome 618786 28229514;30019515;31736240;15385962;19535498;31724824 False 3 100;0;0 30.556 False ENSG00000178691 ENSG00000178691 HGNC:17101 SVBP gene SVBP Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, OMIM:618569;Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, MONDO:0032816 26350204;31363758;30607023 False 3 33;0;67 30.556 False ENSG00000177868 ENSG00000177868 HGNC:29204 SYN1 gene SYN1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Epilepsy, X-linked, with variable learning disabilities and behavior disorders, 300491;EPILEPSY, X-LINKED, WITH VARIABLE LEARNING DISABILITIES AND BEHAVIOR DISORDERS False 3 100;0;0 30.556 False ENSG00000008056 ENSG00000008056 HGNC:11494 SYNCRIP gene SYNCRIP Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Global developmental delay;Intellectual disability;Autism;Myoclonic atonic seizures;Abnormality of nervous system morphology 34157790;30504930;27479843;26350204;23020937 False 3 0;25;75 30.556 False ENSG00000135316 ENSG00000135316 HGNC:16918 SYNGAP1 gene SYNGAP1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual developmental disorder, autosomal dominant 5, OMIM:612621 False 3 100;0;0 30.556 False ENSG00000197283 ENSG00000197283 HGNC:11497 SYNJ1 gene SYNJ1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal early onset refractory seizures and progressive neurological decline;Epileptic encephalopathy, early infantile, 53, 617389 27435091 False 3 100;0;0 30.556 False ENSG00000159082 ENSG00000159082 HGNC:11503 SYP gene SYP Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental Retardation, X-linked;Mental retardation, X-linked 96, 300802;MENTAL RETARDATION X-LINKED SYP-RELATED (MRXSYP) False 3 100;0;0 30.556 False ENSG00000102003 ENSG00000102003 HGNC:11506 SYT1 gene SYT1 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted INTELLECTUAL DISABILITY;SYT1-associated neurodevelopmental disorder 26350204;25705886;30107533 False 3 40;40;20 30.556 False ENSG00000067715 ENSG00000067715 HGNC:11509 SZT2 gene SZT2 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epileptic encephalopathy, early infantile, 18, 615476; developmental delay; non-syndromic intellectual disability; absent developmental milestones 28893434; 23932106; 24324832 False 3 33;67;0 30.556 False ENSG00000198198 ENSG00000198198 HGNC:29040 TACO1 gene TACO1 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex IV deficiency;Multiple respiratory chain complex deficiencies (disorders of protein synthesis);?Mitochondrial complex IV deficiency, 220110;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex IV Deficiency False 3 100;0;0 30.556 False ENSG00000136463 ENSG00000136463 HGNC:24316 TACO1 gene TACO1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial Diseases;Multiple respiratory chain complex deficiencies (disorders of protein synthesis);?Mitochondrial complex IV deficiency, 220110;Isolated complex IV deficiency;Mitochondrial Respiratory Chain Complex IV Deficiency;Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors) 27604308 False 3 100;0;0 30.556 False ENSG00000136463 ENSG00000136463 HGNC:24316 TACO1 gene TACO1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial Leukoencephalopathy 27319982 - mouse model with a missense variant causing loss of the translational activator of TACO1 have isolated complex IV deficiency;25655951;20727754 and 19503089 (same patients) False 3 0;0;0 30.556 False ENSG00000136463 ENSG00000136463 HGNC:24316 TAF1 gene TAF1 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked, syndromic 33, 300966; global developmental delay; intellectual disability 26637982; 25644381; 26350204 False 3 50;0;50 30.556 False ENSG00000147133 ENSG00000147133 HGNC:11535 TAF2 gene TAF2 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder, autosomal recessive 40, OMIM:615599 21937992;22633631;24084144;26350204;34474177 False 3 50;0;50 30.556 False ENSG00000064313 ENSG00000064313 HGNC:11536 TAF4 gene TAF4 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual developmental disorder, autosomal dominant 73, OMIM:620450 27026076;28191890;33875846;35904126 False 3 100;0;0 30.556 False ENSG00000130699 ENSG00000130699 HGNC:11537 TAF6 gene TAF6 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Alazami-Yuan syndrome, 617126;Intellectual disability 25558065;25574841 False 3 100;0;0 30.556 False ENSG00000106290 ENSG00000106290 HGNC:11540 TAF8 gene TAF8 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, OMIM:619972 29648665;35759269 False 3 50;50;0 30.556 False ENSG00000137413 ENSG00000137413 HGNC:17300 TALDO1 gene TALDO1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Transaldolase deficiency 15877206;26238251;21119539;11283793;17095351;27604308;18331807;23315216 False 3 0;0;0 30.556 False ENSG00000177156 ENSG00000177156 HGNC:11559 TAMM41 gene TAMM41 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 56, OMIM:620139 35321494 False 3 100;0;0 30.556 False ENSG00000144559 ENSG00000144559 HGNC:25187 TAMM41 gene TAMM41 Expert Review Green;Literature;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 56, OMIM:620139 35321494 False 3 100;0;0 30.556 False ENSG00000144559 ENSG00000144559 HGNC:25187 TANC2 gene TANC2 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual developmental disorder with autistic features and language delay, with or without seizures, OMIM:618906;intellectual developmental disorder with autistic features and language delay, with or without seizures, MONDO:0030051 26350204;31616000;33160097;30021165 False 3 40;20;40 30.556 False ENSG00000170921 ENSG00000170921 HGNC:30212 TANGO2 gene TANGO2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration 616878 26805782;26805781;30245509 False 3 67;0;33 30.556 False ENSG00000183597 ENSG00000183597 HGNC:25439 TANGO2 gene TANGO2 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration 616878 26805782;26805781 False 3 100;0;0 30.556 False ENSG00000183597 ENSG00000183597 HGNC:25439 TAOK1 gene TAOK1 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Developmental delay with or without intellectual impairment or behavioral abnormalities, OMIM:619575 31230721 False 3 100;0;0 30.556 False ENSG00000160551 ENSG00000160551 HGNC:29259 TAOK2 gene TAOK2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neuronevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 39737487;29467497 False 3 100;0;0 30.556 False ENSG00000149930 ENSG00000149930 HGNC:16835 TARS2 gene TARS2 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 21, OMIM:615918, MONDO:0014398 33153448;24827421;34508595 False 3 100;0;0 30.556 False ENSG00000143374 ENSG00000143374 HGNC:30740 TARS2 gene TARS2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 21, OMIM: 615918;combined oxidative phosphorylation defect type 21,NDO:0014398 39394138;33153448;34508595;37454282 False 3 100;0;0 30.556 False ENSG00000143374 ENSG00000143374 HGNC:30740 TARS2 gene TARS2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 21, OMIM:615918 33153448;24827421;34508595 False 3 100;0;0 30.556 False ENSG00000143374 ENSG00000143374 HGNC:30740 TASP1 gene TASP1 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Suleiman-El-Hattab syndrome, OMIM:618950 29633245;31209944;31350873;35512351 False 3 100;0;0 30.556 False ENSG00000089123 ENSG00000089123 HGNC:15859 TAT gene TAT Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;Tyrosinaemia type II (Disorders of phenylalanine or tyrosine metabolism) 27604308;28255985 False 3 100;0;0 30.556 False ENSG00000198650 ENSG00000198650 HGNC:11573 TAT gene TAT Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Tyrosinemia, type II, 276600;TYROSINEMIA TYPE 2 (TYRO2) False 3 100;0;0 30.556 False ENSG00000198650 ENSG00000198650 HGNC:11573 TAZ gene TAZ Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females BARTH SYNDROME; BTHS 8630491 False 3 33;67;0 30.556 False ENSG00000102125 ENSG00000102125 HGNC:11577 TAZ gene TAZ London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Disorders of mitochondrial membrane lipids (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Barth syndrome, 302060;Methylglutaconic aciduria type II, Barth syndrome (Organic acidurias);Disorders of mitochondrial lipid metabolism 27604308 False 3 100;0;0 30.556 False ENSG00000102125 ENSG00000102125 HGNC:11577 TAZ gene TAZ Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Disorders of mitochondrial lipid metabolism;Barth syndrome, 302060 False 3 100;0;0 30.556 True ENSG00000102125 ENSG00000102125 HGNC:11577 TBC1D20 gene TBC1D20 Expert Review Green;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Warburg micro syndrome 4, 615663;mental retardation;developmental delay 24239381;26063829 False 3 100;0;0 30.556 False ENSG00000125875 ENSG00000125875 HGNC:16133 TBC1D23 gene TBC1D23 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pontocerebellar hypoplasia, type 11, 617695;Intellectual disability 28823707;28823706;28397838 False 3 100;0;0 30.556 False ENSG00000036054 ENSG00000036054 HGNC:25622 TBC1D24 gene TBC1D24 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Myoclonic epilepsy, infantile, familial, 605021Epileptic encephalopathy, early infantile, 16, 615338;NON SYNDROMAL HEARING LOSS False 3 75;0;25 30.556 False ENSG00000162065 ENSG00000162065 HGNC:29203 TBC1D2B gene TBC1D2B Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with seizures and gingival overgrowth, OMIM:619323;neurodevelopmental disorder with seizures and gingival overgrowth, MONDO:0859148 32623794;38374468 False 3 67;33;0 30.556 False ENSG00000167202 ENSG00000167202 HGNC:29183 TBC1D7 gene TBC1D7 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Macrocephaly/megalencephaly syndrome, autosomal recessive, OMIM:248000 23687350;24515783;35584673;36669495 False 3 75;25;0 30.556 False ENSG00000145979 ENSG00000145979 HGNC:21066 TBCD gene TBCD Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum, OMIM:617193;Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, MONDO:0044646 False 3 100;0;0 30.556 False ENSG00000141556 ENSG00000141556 HGNC:11581 TBCE gene TBCE Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Kenny-Caffey syndrome, type 1, OMIM:244460;autosomal recessive Kenny-Caffey syndrome, MONDO:0009486;Hypoparathyroidism-retardation-dysmorphism syndrome, OMIM:241410;hypoparathyroidism-retardation-dysmorphism syndrome, MONDO:0009426 False 3 100;0;0 30.556 False ENSG00000116957 ENSG00000116957 HGNC:11582 TBCK gene TBCK Expert Review Green;Victorian Clinical Genetics Services;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 616900 27040692;25529582 False 3 100;0;0 30.556 False ENSG00000145348 ENSG00000145348 HGNC:28261 TBL1XR1 gene TBL1XR1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted AUTISM 23160955 False 3 100;0;0 30.556 False ENSG00000177565 ENSG00000177565 HGNC:29529 TBR1 gene TBR1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Autism;Intellectual developmental disorder with autism and speech delay, 606053;Abnormal cortical gyration 23160955;30268909;25356899;22495311;30250039 False 3 67;33;0 30.556 False ENSG00000136535 ENSG00000136535 HGNC:11590 TCEAL1 gene TCEAL1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Neurodevelopmental disorder with gait disturbance, dysmorphic facies and behavioral abnormalities, X-linked, OMIM:301094 36368327 False 3 100;0;0 30.556 False ENSG00000172465 ENSG00000172465 HGNC:11616 TCF20 gene TCF20 Expert Review Green;Victorian Clinical Genetics Services;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted TCF20 syndrome;Intellectual disability;developmental delay;Developmental delay with variable intellectual impairment and behavioral abnormalities 618430 27436265;25533962;27479843;28135719;30739909;27436265;25228304;27479843;28333917;28554332;30525188 False 3 100;0;0 30.556 False ENSG00000100207 ENSG00000100207 HGNC:11631 TCF4 gene TCF4 Victorian Clinical Genetics Services;Expert Review Green;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Pitt-Hopkins syndrome, 610954;PITT-HOPKINS SYNDROME (PTHS) 29588831;18728071;17436255;17436254;25529582;24896178 False 3 100;0;0 30.556 False ENSG00000196628 ENSG00000196628 HGNC:11634 TCF7L2 gene TCF7L2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental disorders;Global developmental delay;Intellectual disability;Autism;Attention deficit hyperactivity disorder;Myopia;Abnormality of skeletal system 33057194;34003604 False 3 67;33;0 30.556 False ENSG00000148737 ENSG00000148737 HGNC:11641 TCN2 gene TCN2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Transcobalamin II deficiency;can have a presentation similar to severe combined immunodeficiency;pancytopenia;neutropenic colitis;Agammaglobulinemia;megaloblastic bone marrow;thrombocytopenia;neutropenia;failure to thrive;hypotonia, myoclonic like movements, pallor, purpura, anaemia, thrombocytopenia, megaloblastosis, aplastic bone marrow. PMID: 24305960;7980584;7849710;20352340;18956255 False 3 100;0;0 30.556 False ENSG00000185339 ENSG00000185339 HGNC:11653 TCN2 gene TCN2 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital neutropaenia;Intellectual disability;A- or hypo-gammaglobulinaemia;Agranulocytosis;Combined B and T cell defect;SCID;Transcobalamin II deficiency (Disorders of cobalamin absorption, transport and metabolism) 27604308;19373259 False 3 100;0;0 30.556 False ENSG00000185339 ENSG00000185339 HGNC:11653 TCTN2 gene TCTN2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal JOUBERT SYNDROME AND RELATED DISORDERS 0 False 3 0;100;0 30.556 False ENSG00000168778 ENSG00000168778 HGNC:25774 TCTN3 gene TCTN3 Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Orofaciodigital syndrome IV, 258860;Joubert syndrome 18, 614815 22883145;25118024;26092869 False 3 100;0;0 30.556 False ENSG00000119977 ENSG00000119977 HGNC:24519 TDP2 gene TDP2 Expert Review Green;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spinocerebellar ataxia, autosomal recessive 23, 616949) 24658003;30109272;31410782 False 3 100;0;0 30.556 False ENSG00000111802 ENSG00000111802 HGNC:17768 TECPR2 gene TECPR2 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 49, autosomal recessive, 615031 23176824;26542466;25529582 False 3 25;75;0 30.556 False ENSG00000196663 ENSG00000196663 HGNC:19957 TEFM gene TEFM NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 58, OMIM:620451 36823193 False 3 100;0;0 30.556 False ENSG00000172171 ENSG00000172171 HGNC:26223 TEFM gene TEFM Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 58, OMIM:620451 36823193 False 3 100;0;0 30.556 False ENSG00000172171 ENSG00000172171 HGNC:26223 TEFM gene TEFM Expert Review Green;Literature;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 58, OMIM:620451 36823193 False 3 100;0;0 30.556 False ENSG00000172171 ENSG00000172171 HGNC:26223 TELO2 gene TELO2 Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal You-Hoover-Fong syndrome, 616954, syndromic intellectual disability 27132593;28944240 False 3 100;0;0 30.556 False ENSG00000100726 ENSG00000100726 HGNC:29099 TENM3 gene TENM3 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microphthalmia, syndromic 15, OMIM:615145;?Microphthalmia, isolated, with coloboma 9, OMIM:615145;Microphthalmia, isolated, with coloboma 9, MONDO:0014059 30513139;22766609;27103084;29753094 False 3 100;0;0 30.556 False ENSG00000218336 ENSG00000218336 HGNC:29944 TET3 gene TET3 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Beck-Fahrner syndrome OMIM:618798 31928709 False 3 100;0;0 30.556 False ENSG00000187605 ENSG00000187605 HGNC:28313 TFAM gene TFAM Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 15 (hepatocerebral type), OMIM:617156 27448789;31785789;32399598;34647195 False 3 67;33;0 30.556 False ENSG00000108064 ENSG00000108064 HGNC:11741 TFAM gene TFAM Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 15 (hepatocerebral type), OMIM:617156 27448789;31785789;32399598;34647195 False 3 100;0;0 30.556 False ENSG00000108064 ENSG00000108064 HGNC:11741 TFE3 gene TFE3 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies, OMIM:301066 30595499;31833172;32409512 False 3 100;0;0 30.556 False ENSG00000068323 ENSG00000068323 HGNC:11752 TFG gene TFG Expert Review Green;NHS GMS;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 57, autosomal recessive, OMIM:615658 23479643;27601211;27492651;28124177;29971521;30467354;33767317 False 3 75;0;25 30.556 False ENSG00000114354 ENSG00000114354 HGNC:11758 TFR2 gene TFR2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hemochromatosis, type 3 604250;Hereditary haemochromatosis Type 3 (Disorder of iron metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000106327 ENSG00000106327 HGNC:11762 TGIF1 gene TGIF1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted HOLOPROSENCEPHALY 0 False 3 33;67;0 30.556 False ENSG00000177426 ENSG00000177426 HGNC:11776 TH gene TH Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;Early onset dystonia;Tyrosine hydroxylase deficiency (Disorders of neurotransmitter metabolism, biogenic amines);Parkinson Disease and Complex Parkinsonism 27604308;24753243 False 3 100;0;0 30.556 False ENSG00000180176 ENSG00000180176 HGNC:11782 TH gene TH Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal DOPA-RESPONSIVE DYSTONIA 7814018;17696123;9732974;8528210;21937992;8817341;10585338;9703425;11246459 False 3 33;67;0 30.556 False ENSG00000180176 ENSG00000180176 HGNC:11782 THOC2 gene THOC2 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked 12/35, 300957 26166480; 19377476 False 3 0;33;67 30.556 False ENSG00000125676 ENSG00000125676 HGNC:19073 THOC6 gene THOC6 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Beaulieu-Boycott-Innes syndrome, 613680;Includes developmental delay and mental retardation 23621916 False 3 100;0;0 30.556 False ENSG00000131652 ENSG00000131652 HGNC:28369 THRA gene THRA Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 6 22168587;22494134 False 3 50;50;0 30.556 False ENSG00000126351 ENSG00000126351 HGNC:11796 THUMPD1 gene THUMPD1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with speech delay and variable ocular anomalies, OMIM:619989 30237576;35196516 False 3 57;0;43 30.556 False ENSG00000066654 ENSG00000066654 HGNC:23807 TIAM1 gene TIAM1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with language delay and seizures, OMIM:619908 35240055;33328293 False 3 67;33;0 30.556 False ENSG00000156299 ENSG00000156299 HGNC:11805 TIMM50 gene TIMM50 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-methylglutaconic aciduria, type IX 617698 27573165 False 3 100;0;0 30.556 True ENSG00000105197 ENSG00000105197 HGNC:23656 TIMM50 gene TIMM50 Expert Review Green;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-methylglutaconic aciduria, type IX, 617698 27573165;30190335;31058414;Serajee et al. (ASHG conference 2015 - abstract Nr. 2299T) False 3 100;0;0 30.556 False ENSG00000105197 ENSG00000105197 HGNC:23656 TIMM50 gene TIMM50 Expert Review Green;Literature;Expert Review;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal 3-methylglutaconic aciduria, type IX 617698 27573165 False 3 50;50;0 30.556 False ENSG00000105197 ENSG00000105197 HGNC:23656 TIMM8A gene TIMM8A London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mohr-Tranebjaerg syndrome, 304700;Jensen syndrome, 311150;Disorders of the mitochondrial import system;Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Deafness, X-linked 1, progressive 27604308 False 3 100;0;0 30.556 False ENSG00000126953 ENSG00000126953 HGNC:11817 TIMM8A gene TIMM8A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Disorders of the mitochondrial import system;Deafness, X-linked 1, progressive;Mohr-Tranebjaerg syndrome, 304700;Jensen syndrome, 311150 False 3 100;0;0 30.556 True ENSG00000126953 ENSG00000126953 HGNC:11817 TIMMDC1 gene TIMMDC1 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 31, OMIM:618251 28604674;33278652 False 3 100;0;0 30.556 False ENSG00000113845 ENSG00000113845 HGNC:1321 TIMMDC1 gene TIMMDC1 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex I deficiency, nuclear type 31, OMIM:618251 28604674;33278652 False 3 100;0;0 30.556 False ENSG00000113845 ENSG00000113845 HGNC:1321 TK2 gene TK2 Victorian Clinical Genetics Services;UKGTN;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 2 (myopathic type), OMIM:609560;Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3, OMIM:617069 False 3 100;0;0 30.556 False ENSG00000166548 ENSG00000166548 HGNC:11831 TK2 gene TK2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 2 (myopathic type), OMIM:609560;Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3, OMIM:617069 27604308 False 3 100;0;0 30.556 False ENSG00000166548 ENSG00000166548 HGNC:11831 TLK2 gene TLK2 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Mental retardation, autosomal dominant 57, OMIM:618050;Mental retardation, autosomal dominant 57, MONDO:0054837 27479843;29861108;33323470 False 3 0;0;100 30.556 False ENSG00000146872 ENSG00000146872 HGNC:11842 TMCO1 gene TMCO1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, 614132;CRANIOFACIAL DYSMORPHISM, SKELETAL ANOMALIES, AND MENTAL RETARDATION SYNDROME False 3 100;0;0 30.556 False ENSG00000143183 ENSG00000143183 HGNC:18188 TMEM106B gene TMEM106B Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Leukodystrophy, hypomyelinating, 16, OMIM:617964;Leukodystrophy, hypomyelinating, 16, MONDO:0054791 29186371;29444210;30643851;32595021 False 3 100;0;0 30.556 False ENSG00000106460 ENSG00000106460 HGNC:22407 TMEM106B gene TMEM106B Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Leukodystrophy, hypomyelinating, 16, OMIM:617964;Leukodystrophy, hypomyelinating, 16, MONDO:0054791 29186371;29444210;30643851;32595021 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000106460 ENSG00000106460 HGNC:22407 TMEM126B gene TMEM126B Expert Review Green;Victorian Clinical Genetics Services;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency 27374774;27374773 False 3 50;50;0 30.556 False ENSG00000171204 ENSG00000171204 HGNC:30883 TMEM126B gene TMEM126B Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex I deficiency 27374773;27374774 False 3 50;50;0 30.556 False ENSG00000171204 ENSG00000171204 HGNC:30883 TMEM147 gene TMEM147 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-Pelger-Huet anomaly, OMIM:620075 36044892 False 3 100;0;0 30.556 False ENSG00000105677 ENSG00000105677 HGNC:30414 TMEM165 gene TMEM165 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIk 614727;CDG2K (other congenital disorders of glycosylation) 27604308 False 3 0;0;0 30.556 False ENSG00000134851 ENSG00000134851 HGNC:30760 TMEM165 gene TMEM165 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIk, 614727;CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIK False 3 100;0;0 30.556 False ENSG00000134851 ENSG00000134851 HGNC:30760 TMEM199 gene TMEM199 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital disorder of glycosylation, type IIp 616829 26833330 False 3 0;0;0 30.556 False ENSG00000244045 ENSG00000244045 HGNC:18085 TMEM216 gene TMEM216 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal JOUBERT SYNDROME 2 20036350;20512146 False 3 0;100;0 30.556 False ENSG00000187049 ENSG00000187049 HGNC:25018 TMEM222 gene TMEM222 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with motor and speech delay and behavioral abnormalities, OMIM:619470 33824500;27457812 False 3 100;0;0 30.556 False ENSG00000186501 ENSG00000186501 HGNC:25363 TMEM237 gene TMEM237 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Joubert syndrome 14, 614424;JOUBERT SYNDROME 14 False 3 100;0;0 30.556 False ENSG00000155755 ENSG00000155755 HGNC:14432 TMEM240 gene TMEM240 Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Spinocerebellar ataxia 21, 607454 25070513 False 3 100;0;0 30.556 False ENSG00000205090 ENSG00000205090 HGNC:25186 TMEM5 gene TMEM5 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal SEVERE COBBLESTONE LISSENCEPHALY 23217329;23519211 False 3 33;67;0 30.556 False ENSG00000118600 ENSG00000118600 HGNC:13530 TMEM5 gene TMEM5 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10 27212206 False 3 0;0;0 30.556 False ENSG00000118600 ENSG00000118600 HGNC:13530 TMEM63A gene TMEM63A Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Leukodystrophy, hypomyelinating, 19, transient infantile, OMIM:618688 31587869;33597727;33785861 False 3 100;0;0 30.556 False ENSG00000196187 ENSG00000196187 HGNC:29118 TMEM63B gene TMEM63B NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Developmental and epileptic encephalopathy 118, OMIM:621250 37421948 False 3 100;0;0 30.556 False ENSG00000137216 ENSG00000137216 HGNC:17735 TMEM63C gene TMEM63C Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 87, autosomal recessive, OMIM:619966 35718349 False 3 100;0;0 30.556 False ENSG00000165548 ENSG00000165548 HGNC:23787 TMEM67 gene TMEM67 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Meckel syndrome 3, 607361Joubert syndrome 6, 610688{Bardet-Biedl syndrome 14, modifier of}, 209900COACH syndrome, 216360Nephronophthisis 11, 613550;COACH SYNDROME(COACHS) False 3 100;0;0 30.556 False ENSG00000164953 ENSG00000164953 HGNC:28396 TMEM70 gene TMEM70 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2 18953340;21147908 False 3 33;67;0 30.556 False ENSG00000175606 ENSG00000175606 HGNC:26050 TMEM70 gene TMEM70 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial Diseases;Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, 614052;Isolated complex V deficiency;Complex V (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors);Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2;Mitochondrial Complex V (ATP Synthase) Deficiency, Nuclear Type 27604308 False 3 100;0;0 30.556 False ENSG00000175606 ENSG00000175606 HGNC:26050 TMEM70 gene TMEM70 Victorian Clinical Genetics Services;Emory Genetics Laboratory;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex V deficiency;Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, 614052;Mitochondrial Complex V (ATP Synthase) Deficiency, Nuclear Type;Mitochondrial Diseases False 3 100;0;0 30.556 False ENSG00000175606 ENSG00000175606 HGNC:26050 TMEM94 gene TMEM94 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder with cardiac defects and dysmorphic facies, OMIM:618316 30526868 False 3 0;100;0 30.556 False ENSG00000177728 ENSG00000177728 HGNC:28983 TMTC3 gene TMTC3 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Lissencephaly 8, 617255;includes intellectual disability False 3 100;0;0 30.556 False ENSG00000139324 ENSG00000139324 HGNC:26899 TMX2 gene TMX2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, OMIM:618730;Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, MONDO:0032887 31586943;31270415;31735293 False 3 100;0;0 30.556 False ENSG00000213593 ENSG00000213593 HGNC:30739 TNPO2 gene TNPO2 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual disability;Dysmorphic features;Microcephaly;Seizures;Hypotonia 26350204;34314705 False 3 25;0;75 30.556 False ENSG00000105576 ENSG00000105576 HGNC:19998 TNR gene TNR Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus, OMIM:619653 28334938;32099069 False 3 100;0;0 30.556 False ENSG00000116147 ENSG00000116147 HGNC:11953 TNRC6B gene TNRC6B Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Global developmental delay;Intellectual disability;Autistic behaviour 32152250;28135719;25363768;27479843;28959963;25228304 False 3 100;0;0 30.556 False ENSG00000100354 ENSG00000100354 HGNC:29190 TOE1 gene TOE1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pontocerebellar hypoplasia, type 7 614969 28092684 False 3 100;0;0 30.556 False ENSG00000132773 ENSG00000132773 HGNC:15954 TOMM7 gene TOMM7 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Garg-Mishra progeroid syndrome, OMIM:620601;Garg-Mishra progeroid syndrome, MONDO:0957953 36282599;36299998;39333057 False 3 50;50;0 30.556 False ENSG00000196683 ENSG00000196683 HGNC:21648 TOMM7 gene TOMM7 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Garg-Mishra progeroid syndrome, OMIM:620601;Garg-Mishra progeroid syndrome, MONDO:0957953 36282599;36299998;39333057 False 3 67;33;0 30.556 False ENSG00000196683 ENSG00000196683 HGNC:21648 TOP3A gene TOP3A Expert Review Green;Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 5, 618098 29290614 False 3 0;0;100 30.556 False ENSG00000177302 ENSG00000177302 HGNC:11992 TOP3A gene TOP3A Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 5, 618098 29290614 False 3 0;0;100 30.556 False ENSG00000177302 ENSG00000177302 HGNC:11992 TOR1A gene TOR1A NHS GMS;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Arthrogryposis multiplex congenita 5, OMIM:618947;Arthrogryposis multiplex congenita 5, MONDO:0100218 30244176;29053766;28516161;24896178 False 3 67;0;33 30.556 False ENSG00000136827 ENSG00000136827 HGNC:3098 TP73 gene TP73 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ciliary dyskinesia, primary, 47, and lissencephaly, OMIM:619466 31130284;34077761 False 3 100;0;0 30.556 False ENSG00000078900 ENSG00000078900 HGNC:12003 TPK1 gene TPK1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type), 614458 False 3 100;0;0 30.556 True ENSG00000196511 ENSG00000196511 HGNC:17358 TPK1 gene TPK1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type), 614458 False 3 100;0;0 30.556 False ENSG00000196511 ENSG00000196511 HGNC:17358 TPP1 gene TPP1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Ceroid lipofuscinosis, neuronal, 2, 204500;NEURONAL CEROID LIPOFUSCINOSIS TYPE 2 (CLN2) False 3 100;0;0 30.556 False ENSG00000166340 ENSG00000166340 HGNC:2073 TPP1 gene TPP1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;Ceroid lipofuscinosis, neuronal, 2;CLN2, Jansky-Bielschowsky disease (Ceroid lipfuscinoses, neuronal);Hereditary ataxia 27604308 False 3 0;0;0 30.556 False ENSG00000166340 ENSG00000166340 HGNC:2073 TPP2 gene TPP2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Immunodeficiency 78 with autoimmunity and developmental delay, OMIM:619220 33586135;25414442;25525876;30533531 False 3 100;0;0 30.556 False ENSG00000134900 ENSG00000134900 HGNC:12016 TRA2B gene TRA2B Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Ramond-Elliott neurodevelopmental syndrome, OMIM:621421 36549593 False 3 100;0;0 30.556 False ENSG00000136527 ENSG00000136527 HGNC:10781 TRAF7 gene TRAF7 Expert Review Green;Literature;Expert Review Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Cardiac, facial, and digital anomalies with developmental delay, 618164;Global developmental delay;Abnormal heart morphology;Abnormality of digit;Abnormality of limbs 29961569;27479843;28135719;25363760;25961944 False 3 100;0;0 30.556 False ENSG00000131653 ENSG00000131653 HGNC:20456 TRAIP gene TRAIP Literature;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Seckel syndrome 9, OMIM:616777 26595769;30914295 False 3 100;0;0 30.556 False ENSG00000183763 ENSG00000183763 HGNC:30764 TRAP1 gene TRAP1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal VACTERL;CAKUT PMID: 24152966 - recessive mutations reported in 2 families with CAKUT, and 3 families with VACTERL. False 3 100;0;0 30.556 False ENSG00000126602 ENSG00000126602 HGNC:16264 TRAPPC12 gene TRAPPC12 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, OMIM:617669;Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome, MONDO:0044696 28777934;32369837 False 3 100;0;0 30.556 False ENSG00000171853 ENSG00000171853 HGNC:24284 TRAPPC4 gene TRAPPC4 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy, 618741 31794024 False 3 100;0;0 30.556 False ENSG00000196655 ENSG00000196655 HGNC:19943 TRAPPC6B gene TRAPPC6B Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy, OMIM:617862 28626029;28397838;31687267 False 3 50;50;0 30.556 False ENSG00000182400 ENSG00000182400 HGNC:23066 TRAPPC9 gene TRAPPC9 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mental retardation, autosomal recessive 13, OMIM:613192 20004763;20004764;20004765;21629298;22549410;22989526;29031008;30853973 False 3 100;0;0 30.556 False ENSG00000167632 ENSG00000167632 HGNC:30832 TREM2 gene TREM2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY;Calcifications in basal ganglia;Nasu-Hakola disease;Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) 12080485;15883308 False 3 0;0;0 30.556 False ENSG00000095970 ENSG00000095970 HGNC:17761 TREX1 gene TREX1 Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Aicardi-Goutieres syndrome 1, dominant and recessive 225750;General Leukodystrophy & Mitochondrial Leukoencephalopathy;Aicardi-Gouti res syndrome, isolated chilblains, lupus-like disease, retinal vasculopathy with cerebral leukodystrophy;Aicardi-Goutieres syndrome 1, dominant and recessive;Vasculopathy, retinal, with cerebral leukodystrophy 192315 25604658 False 3 0;0;0 30.556 False ENSG00000213689 ENSG00000213689 HGNC:12269 TREX1 gene TREX1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Intellectual disability;Familial cerebral small vessel disease;Intracerebral calcification disorders;(Disorders of nucleotide metabolism, Aicardi-Gouti res Syndrome) AGS1;Inherited white matter disorders 27604308;12624136;25604658 False 3 100;0;0 30.556 False ENSG00000213689 ENSG00000213689 HGNC:12269 TREX1 gene TREX1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Aicardi-Goutieres syndrome 1, dominant and recessive, 225750Chilblain lupus, 610448Vasculopathy, retinal, with cerebral leukodystrophy, 192315{Systemic lupus erythematosus, susceptibility to}, 152700;AICARDI-GOUTIERES SYNDROME 1, DOMINANT AND RECESSIVE False 3 100;0;0 30.556 False ENSG00000213689 ENSG00000213689 HGNC:12269 TRIM37 gene TRIM37 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mulibrey nanism (Other peroxisomal disorders);Mulibrey nanism 27604308 False 3 0;0;0 30.556 False ENSG00000108395 ENSG00000108395 HGNC:7523 TRIM8 gene TRIM8 Expert Review Green;Literature;Expert Review Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Global developmental delay;Intellectual disability;Seizures 30244534;27346735;23934111 False 3 100;0;0 30.556 False ENSG00000171206 ENSG00000171206 HGNC:15579 TRIO gene TRIO Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Intellectual developmental disorder, autosomal dominant 44, with microcephaly, OMIM:617061;Intellectual developmental disorder, autosomal dominant 63, with macrocephaly, OMIM:618825 26721934;27418539;32109419 False 3 100;0;0 30.556 False ENSG00000038382 ENSG00000038382 HGNC:12303 TRIP12 gene TRIP12 Expert Review Green;Victorian Clinical Genetics Services;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown "Mental retardation, autosomal dominant 49 617752" False 3 100;0;0 30.556 False ENSG00000153827 ENSG00000153827 HGNC:12306 TRIT1 gene TRIT1 Expert Review Green;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 35, OMIM :617873;combined oxidative phosphorylation deficiency 35, MONDO:0054742 24901367;28185376 False 3 100;0;0 30.556 False ENSG00000043514 ENSG00000043514 HGNC:20286 TRIT1 gene TRIT1 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 35, OMIM:617873;combined oxidative phosphorylation deficiency 35, MONDO:0054742 28185376; 24901367 False 3 100;0;0 30.556 False ENSG00000043514 ENSG00000043514 HGNC:20286 TRIT1 gene TRIT1 Expert Review Green;Victorian Clinical Genetics Services;Expert list;Expert;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 35, OMIM:617873;combined oxidative phosphorylation deficiency 35, MONDO:0054742 28185376;24901367 False 3 100;0;0 30.556 False ENSG00000043514 ENSG00000043514 HGNC:20286 TRMT1 gene TRMT1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal autosomal recessive intellectual disorder;ARID;Mental retardation, autosomal recessive 68, 618302;Global developmental delay;Intellectual disability 21937992;26308914;30289604;28784718 False 3 25;25;50 30.556 False ENSG00000104907 ENSG00000104907 HGNC:25980 TRMT10A gene TRMT10A Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly, short stature, and impaired glucose metabolism 1, 616033;Young onset diabetes, short stature and microcephaly with intellectual disability 26535115; 26526202; 24204302; 25053765; 26297882 False 3 100;0;0 30.556 False ENSG00000145331 ENSG00000145331 HGNC:28403 TRMT10C gene TRMT10C Expert Review Green;Expert Review Green;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 30, 616974 27132592 False 3 0;100;0 30.556 False ENSG00000174173 ENSG00000174173 HGNC:26022 TRMT10C gene TRMT10C Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 30, 616974 27132592 False 3 0;100;0 30.556 False ENSG00000174173 ENSG00000174173 HGNC:26022 TRMT5 gene TRMT5 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay, OMIM:616539 35342985;26189817;29021354 False 3 100;0;0 30.556 False ENSG00000126814 ENSG00000126814 HGNC:23141 TRMT5 gene TRMT5 Expert Review Green;Victorian Clinical Genetics Services;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay, OMIM:616539 26189817;29021354 False 3 100;0;0 30.556 True ENSG00000126814 ENSG00000126814 HGNC:23141 TRMT5 gene TRMT5 Expert Review Green;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay, OMIM:616539 29021354;26189817 False 3 100;0;0 30.556 False ENSG00000126814 ENSG00000126814 HGNC:23141 TRMU gene TRMU London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal {Deafness, mitochondrial, modifier of}, 580000;Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Liver failure, transient infantile, 613070 27604308 False 3 100;0;0 30.556 False ENSG00000100416 ENSG00000100416 HGNC:25481 TRMU gene TRMU Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);{Deafness, mitochondrial, modifier of}, 580000;Liver failure, transient infantile, 613070 False 3 100;0;0 30.556 True ENSG00000100416 ENSG00000100416 HGNC:25481 TRNT1 gene TRNT1 Victorian Clinical Genetics Services;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal congenital sideroblastic anemia with B cell immunodeficiency, fevers, and developmental delay (SIFD); retinitis pigmentosa with erythrocytic microcytosis PMID: 25652405;PMID: 26494905 False 3 100;0;0 30.556 True ENSG00000072756 ENSG00000072756 HGNC:17341 TRNT1 gene TRNT1 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay, OMIM #616084 25193871;23553769;29170023;25652405;27370603 False 3 100;0;0 30.556 False ENSG00000072756 ENSG00000072756 HGNC:17341 TRNT1 gene TRNT1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal congenital sideroblastic anemia with B cell immunodeficiency, fevers, and developmental delay (SIFD);retinitis pigmentosa with erythrocytic microcytosis 25652405;26494905 False 3 100;0;0 30.556 False ENSG00000072756 ENSG00000072756 HGNC:17341 TRPM3 gene TRPM3 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures, OMIM:620224 31278393;32439617;32343227;32427099 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000083067 ENSG00000083067 HGNC:17992 TRPM6 gene TRPM6 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypomagnesemia 1, intestinal 602014;Hypomagnesaemia type 1, intestinal (Disorder of magnesium metabolism) 27604308;23942199;12032570 False 3 100;0;0 30.556 False ENSG00000119121 ENSG00000119121 HGNC:17995 TRPM7 gene TRPM7 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown hypomagnesaemia with secondary hypocalcaemia 39099563;35712613;35561741 False 3 100;0;0 30.556 False ENSG00000092439 ENSG00000092439 HGNC:17994 TRRAP gene TRRAP Expert Review;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Microcephaly;Seizures;Abnormal heart morphology;Autism;Developmental delay with or without dysmorphic facies and autism, 603015;Intellectual disability;Abnormality of the urinary system;Global developmental delay 30827496;30424743 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000196367 ENSG00000196367 HGNC:12347 TSC1 gene TSC1 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Tuberous sclerosis-1, 191100Lymphangioleiomyomatosis, 606690;Focal cortical dysplasia, Taylor balloon cell type, 607341;TUBEROUS SCLEROSIS TYPE 1 (TSC1) 28215400;19175396;16114042;12112044 False 3 100;0;0 30.556 False ENSG00000165699 ENSG00000165699 HGNC:12362 TSC2 gene TSC2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Tuberous sclerosis-2, 613254Lymphangioleiomyomatosis, somatic, 606690;LYMPHANGIOLEIOMYOMATOSIS (LAM) 25529582;24896178 False 3 100;0;0 30.556 False ENSG00000103197 ENSG00000103197 HGNC:12363 TSEN2 gene TSEN2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal PONTOCEREBELLAR HYPOPLASIA TYPE 2 AND TYPE 4 0 False 3 100;0;0 30.556 False ENSG00000154743 ENSG00000154743 HGNC:28422 TSEN34 gene TSEN34 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pontocerebellar hypoplasia type 2C, OMIM:612390;pontocerebellar hypoplasia type 2C, MONDO:0012891 20952379;27370523;32476018;37544645 False 3 67;33;0 30.556 False ENSG00000170892 ENSG00000170892 HGNC:15506 TSEN54 gene TSEN54 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Pontocerebellar hypoplasia type 5, OMIM:610204;Pontocerebellar hypoplasia type 2A, OMIM:277470;Pontocerebellar hypoplasia type 4, OMIM:225753 16470708;20956791;20952379 False 3 100;0;0 30.556 False ENSG00000182173 ENSG00000182173 HGNC:27561 TSFM gene TSFM London North GLH;NHS GMS;Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 3, 610505;Combined oxidative phosphorylation deficiency 3 610505;Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) 27604308 False 3 100;0;0 30.556 False ENSG00000123297 ENSG00000123297 HGNC:12367 TSFM gene TSFM Expert Review Green;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 3 610505 False 3 100;0;0 30.556 False ENSG00000123297 ENSG00000123297 HGNC:12367 TSFM gene TSFM Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 3, 610505 27604308;17033963;25037205 False 3 100;0;0 30.556 False ENSG00000123297 ENSG00000123297 HGNC:12367 TSHB gene TSHB Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal HYPOTHRYOIDISM, CONGENITAL, NONGOITROUS 4 2792087 False 3 33;67;0 30.556 False ENSG00000134200 ENSG00000134200 HGNC:12372 TSPOAP1 gene TSPOAP1 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dystonia, intellectual disability and cerebellar atrophy 33539324 False 3 100;0;0 30.556 False ENSG00000005379 ENSG00000005379 HGNC:16831 TTC19 gene TTC19 Victorian Clinical Genetics Services;Illumina TruGenome Clinical Sequencing Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Isolated complex III deficiency;Mitochondrial complex III deficiency, nuclear type 2, 615157;Mitochondrial Diseases;Mitochondrial Respiratory Chain Complex III Deficiency False 3 100;0;0 30.556 False ENSG00000011295 ENSG00000011295 HGNC:26006 TTC19 gene TTC19 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MITOCHONDRIAL COMPLEX III DEFICIENCY 0 False 3 33;67;0 30.556 False ENSG00000011295 ENSG00000011295 HGNC:26006 TTC19 gene TTC19 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial Diseases;Isolated complex III deficiency;Mitochondrial Respiratory Chain Complex III Deficiency;Complex III (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors);Mitochondrial complex III deficiency, nuclear type 2, 615157 27604308 False 3 100;0;0 30.556 False ENSG00000011295 ENSG00000011295 HGNC:26006 TTC37 gene TTC37 Expert Review Green;Victorian Clinical Genetics Services;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Trichohepatoenteric syndrome 1, 222470 False 3 100;0;0 30.556 False ENSG00000198677 ENSG00000198677 HGNC:23639 TTC37 gene TTC37 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Infantile enterocolitis & monogenic inflammatory bowel disease;Trichohepatoenteric syndrome 1 (Other metabolic disorders) 27604308;25976726;28292286;31132033 False 3 67;0;33 30.556 False ENSG00000198677 ENSG00000198677 HGNC:23639 TTC5 gene TTC5 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism, OMIM:619244 29302074;32439809 False 3 100;0;0 30.556 False ENSG00000136319 ENSG00000136319 HGNC:19274 TTC8 gene TTC8 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Bardet-Biedl syndrome 8, 209900Retinitis pigmentosa 51, 613464;RETINITIS PIGMENTOSA TYPE 51 (RP51) False 3 100;0;0 30.556 False ENSG00000165533 ENSG00000165533 HGNC:20087 TTI1 gene TTI1 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with microcephaly and movement abnormalities, OMIM:620445 36724785 False 3 100;0;0 30.556 False ENSG00000101407 ENSG00000101407 HGNC:29029 TTI2 gene TTI2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal AUTOSOMAL RECESSIVE MENTAL RETARDATION;Mental retardation, autosomal recessive 39, 615541 21937992;23956177 False 3 100;0;0 30.556 False ENSG00000129696 ENSG00000129696 HGNC:26262 TTPA gene TTPA Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal TTP1 deficiency (Other disorders of vitamins and cofactors);Hereditary ataxia 27604308;26981194 False 3 100;0;0 30.556 False ENSG00000137561 ENSG00000137561 HGNC:12404 TUBA1A gene TUBA1A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Lissencephaly 3, 611603;INTELLECTUAL DISABILITY False 3 100;0;0 30.556 False ENSG00000167552 ENSG00000167552 HGNC:20766 TUBB gene TUBB Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 6 23246003 False 3 33;67;0 30.556 False ENSG00000196230 ENSG00000196230 HGNC:20778 TUBB2A gene TUBB2A Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Cortical dysplasia, complex, with other brain malformations 5, OMIM:615763;Complex cortical dysplasia with other brain malformations 5, MONDO:0014337 24702957;32571897 False 3 50;50;0 30.556 False ENSG00000137267 ENSG00000137267 HGNC:12412 TUBB2B gene TUBB2B Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Cortical dysplasia, complex, with other brain malformations 7, OMIM:610031 False 3 100;0;0 30.556 False ENSG00000137285 ENSG00000137285 HGNC:30829 TUBB3 gene TUBB3 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted CONGENITAL FIBROSIS OF THE EXTRAOCULAR MUSCLES 20074521 False 3 0;100;0 30.556 False ENSG00000258947 ENSG00000258947 HGNC:20772 TUBB4A gene TUBB4A Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Leukodystrophy, hypomyelinating, 6, 612438;General Leukodystrophy & Mitochondrial Leukoencephalopathy;Leukodystrophy, hypomyelinating 6;Dystonia 4, torsion, autosomal dominant, 128101 25655951 False 3 0;0;0 30.556 False ENSG00000104833 ENSG00000104833 HGNC:20774 TUBB4A gene TUBB4A Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted HYPOMYELINATION WITH ATROPHY OF THE BASAL GANGLIA AND CEREBELLUM (H-ABC) 23582646 False 3 33;67;0 30.556 False ENSG00000104833 ENSG00000104833 HGNC:20774 TUBG1 gene TUBG1 Expert Review Green;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Cortical dysplasia, complex, with other brain malformations 4, 615412 23603762;24860126;27010057;29706637;31151415 False 3 100;0;0 30.556 False ENSG00000131462 ENSG00000131462 HGNC:12417 TUBGCP2 gene TUBGCP2 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, OMIM:618737 31630790;40017707 False 3 100;0;0 30.556 False ENSG00000130640 ENSG00000130640 HGNC:18599 TUBGCP6 gene TUBGCP6 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal MICROCEPHALY AND CHORIORETINOPATHY WITH OR WITHOUT MENTAL RETARDATION 22279524 False 3 100;0;0 30.556 False ENSG00000128159 ENSG00000128159 HGNC:18127 TUFM gene TUFM Expert Review Green;Expert Review Green;London North GLH;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 4 610678;Combined oxidative phosphorylation deficiency 4, 610678 26741492;17160893;25735936;28132884 False 3 100;0;0 30.556 False ENSG00000178952 ENSG00000178952 HGNC:12420 TUFM gene TUFM Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial Leukoencephalopathy;Combined oxidative phosphorylation deficiency 4, OMIM:610678 25735936;25655951;17160893;28132884;26741492 False 3 100;0;0 30.556 False ENSG00000178952 ENSG00000178952 HGNC:12420 TUFM gene TUFM Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 4 610678 28132884;25735936;17160893;26741492 False 3 100;0;0 30.556 False ENSG00000178952 ENSG00000178952 HGNC:12420 TUSC3 gene TUSC3 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder, autosomal recessive 7, OMIM:611093 18452889;18455129;21739581;26864433;27148795 False 3 0;0;0 30.556 False ENSG00000104723 ENSG00000104723 HGNC:30242 TUSC3 gene TUSC3 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder, autosomal recessive 7, OMIM:611093 18452889;18455129;21739581;27148795 False 3 100;0;0 30.556 False ENSG00000104723 ENSG00000104723 HGNC:30242 TWIST1 gene TWIST1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted SAETHRE-CHOTZEN SYNDROME 17343269 False 3 33;67;0 30.556 False ENSG00000122691 ENSG00000122691 HGNC:12428 TWNK gene TWNK Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 7;General Leukodystrophy & Mitochondrial Leukoencephalopathy;Mitochondrial Leukoencephalopathy 25655951 False 3 0;0;0 30.556 False ENSG00000107815 ENSG00000107815 HGNC:1160 TWNK gene TWNK London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), OMIM:271245 (AR);Perrault syndrome 5, OMIM:616138 (AR);Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, OMIM:609286 (AD) 27604308 False 3 100;0;0 30.556 False ENSG00000107815 ENSG00000107815 HGNC:1160 TWNK gene TWNK Victorian Clinical Genetics Services;UKGTN;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), OMIM:271245;Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, OMIM:609286;Perrault syndrome 5, OMIM:616138 False 3 100;0;0 30.556 False ENSG00000107815 ENSG00000107815 HGNC:1160 TYMP gene TYMP Victorian Clinical Genetics Services;UKGTN;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Disorders of mitochondrial DNA maintenance and integrity;Mitochondrial DNA depletion syndrome 1 (MNGIE type), 603041;Mitochondrial Neurogastrointestinal Encephalopathy Disease False 3 100;0;0 30.556 False ENSG00000025708 ENSG00000025708 HGNC:3148 TYMP gene TYMP Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial Leukoencephalopathy;Mitochondrial DNA depletion syndrome 1 (MNGIE type) 25655951 False 3 0;0;0 30.556 False ENSG00000025708 ENSG00000025708 HGNC:3148 TYMP gene TYMP London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Thymidine phosphorylase deficiency (Disorders of pyrimidine metabolism);Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Disorders of mitochondrial DNA maintenance and integrity;Mitochondrial Neurogastrointestinal Encephalopathy Disease;Mitochondrial DNA depletion syndrome 1 (MNGIE type), 603041 27604308;24816252 False 3 100;0;0 30.556 False ENSG00000025708 ENSG00000025708 HGNC:3148 U2AF2 gene U2AF2 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 28135719;31785789;33057194;34112922;36747105;37092751;37134193 False 3 75;25;0 30.556 False ENSG00000063244 ENSG00000063244 HGNC:23156 UBA5 gene UBA5 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epileptic encephalopathy, early infantile, 44, 617132;Intellectual disability 25529582;27545674;27545681 False 3 100;0;0 30.556 False ENSG00000081307 ENSG00000081307 HGNC:23230 UBAP2L gene UBAP2L Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies, OMIM:620494 35977029 False 3 100;0;0 30.556 False ENSG00000143569 ENSG00000143569 HGNC:29877 UBE2A gene UBE2A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked syndromic, Nascimento-type, 300860;UBE2A-RELATED X-LINKED SYNDROMIC MENTAL RETARDATION False 3 100;0;0 30.556 False ENSG00000077721 ENSG00000077721 HGNC:12472 UBE3A gene UBE3A Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) Angelman syndrome, 105830;ANGELMAN SYNDROME False 3 100;0;0 30.556 False ENSG00000114062 ENSG00000114062 HGNC:12496 UBE3B gene UBE3B Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal BLEPHAROPHIMOSIS-MENTAL RETARDATION 21567902;23200864 False 3 100;0;0 30.556 False ENSG00000151148 ENSG00000151148 HGNC:13478 UBE4A gene UBE4A Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability 33420346 False 3 100;0;0 30.556 False ENSG00000110344 ENSG00000110344 HGNC:12499 UBR1 gene UBR1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Johanson-Blizzard syndrome, 243800;JOHANSON-BLIZZARD SYNDROME (JBS) False 3 100;0;0 30.556 False ENSG00000159459 ENSG00000159459 HGNC:16808 UBR5 gene UBR5 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted complex neurodevelopmental disorder, MONDO:0100038 39721588 False 3 100;0;0 30.556 False ENSG00000104517 ENSG00000104517 HGNC:16806 UBR7 gene UBR7 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;epilepsy;hypothyroidism;congenital anomalies;dysmorphic features 21937992;33340455 False 3 25;0;75 30.556 False ENSG00000012963 ENSG00000012963 HGNC:20344 UBTF gene UBTF Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodegeneration, childhood-onset, with brain atrophy, OMIM:617672 28777933;29300972;30517966;31931739;33026538 False 3 33;0;67 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000108312 ENSG00000108312 HGNC:12511 UFM1 gene UFM1 Expert Review Green;Literature;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal global developmental delay with progressive microcephaly;Leukodystrophy hypomyelinating 14, 617899;Leukodystrophy, hypomyelinating, 14, 617899 28931644;29868776;30914295 False 3 100;0;0 30.556 False ENSG00000120686 ENSG00000120686 HGNC:20597 UFM1 gene UFM1 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 14, OMIM:617899 28931644;29868776 False 3 100;0;0 30.556 False ENSG00000120686 ENSG00000120686 HGNC:20597 UFSP2 gene UFSP2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Abnormal muscle tone;Seizures;Global developmental delay;Delayed speech and language development;Intellectual disability;Strabismus 33473208 False 3 100;0;0 30.556 False ENSG00000109775 ENSG00000109775 HGNC:25640 UGDH gene UGDH Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Epileptic encephalopathy, early infantile, 84 - MIM #618792 32001716 False 3 100;0;0 30.556 False ENSG00000109814 ENSG00000109814 HGNC:12525 UGGT1 gene UGGT1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal congenital disorder of glycosylation, MONDO:0015286 40267907 False 3 100;0;0 30.556 False ENSG00000136731 ENSG00000136731 HGNC:15663 UGGT1 gene UGGT1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal congenital disorder of glycosylation, MONDO:0015286 40267907 False 3 100;0;0 30.556 False ENSG00000136731 ENSG00000136731 HGNC:15663 UGP2 gene UGP2 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Developmental and epileptic encephalopathy 83, OMIM:618744 31820119 False 3 100;0;0 30.556 False ENSG00000169764 ENSG00000169764 HGNC:12527 UGT1A1 gene UGT1A1 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Crigler-Najjar syndrome, type I 218800;Bilirubin UDP-glucuronosyltransferase 1 deficiency (Disorders of bile acid metabolism and transport);Crigler-Najjar syndrome, type II 606785 27604308;24816252 False 3 100;0;0 30.556 False ENSG00000241635 ENSG00000241635 HGNC:12530 UMOD gene UMOD Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Cystic kidney disease;Unexplained kidney failure in young people;Familial juvenile hyperuricaemic nephropathy (Disorders of purine metabolism) 27604308;31422399;29180396 False 3 100;0;0 30.556 False ENSG00000169344 ENSG00000169344 HGNC:12559 UMPS gene UMPS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;Orotic aciduria;Orotic aciduria (Disorders of pyrimidine metabolism) 27604308;9042911 False 3 0;0;0 30.556 False ENSG00000114491 ENSG00000114491 HGNC:12563 UMPS gene UMPS Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal OROTIC ACIDURIA TYPE 1 (ORAC1) 9042911 False 3 33;67;0 30.556 False ENSG00000114491 ENSG00000114491 HGNC:12563 UNC13A gene UNC13A Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Neurodevelopmental disorder with speech delay, movement abnormalities, and seizures, OMIM:621456;Neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, OMIM:621455;?Intellectual development disorder with seizures and dysmorphic facies , OMIM:621457 28192369;39634123;41125872 False 3 50;25;25 30.556 False ENSG00000130477 ENSG00000130477 HGNC:23150 UNC80 gene UNC80 Victorian Clinical Genetics Services;Expert Review Green;Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, OMIM:616801 26708751;26708753;26545877;29572195 False 3 100;0;0 30.556 False ENSG00000144406 ENSG00000144406 HGNC:26582 UPB1 gene UPB1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Beta-ureidopropionase deficiency (Disorders of pyrimidine metabolism);Beta-ureidopropionase deficiency 613161 27604308;24526388;25638458;22525402;15385443;17964839 False 3 50;0;50 30.556 False ENSG00000100024 ENSG00000100024 HGNC:16297 UPF1 gene UPF1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 28135719;28539120;33057194;39571789;39993774 False 3 75;25;0 30.556 False ENSG00000005007 ENSG00000005007 HGNC:9962 UPF3B gene UPF3B Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental Retardation, X-linked;Mental retardation, X-linked, syndromic 14, 300676;MENTAL RETARDATION SYNDROMIC X-LINKED TYPE 14 (MRXS14) False 3 100;0;0 30.556 False ENSG00000125351 ENSG00000125351 HGNC:20439 UQCC2 gene UQCC2 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex III deficiency, nuclear type 7, OMIM:615824 28804536;24385928 False 3 50;50;0 30.556 False ENSG00000137288 ENSG00000137288 HGNC:21237 UQCC2 gene UQCC2 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex III deficiency, nuclear type 7, OMIM:615824 28804536;24385928 False 3 50;50;0 30.556 False ENSG00000137288 ENSG00000137288 HGNC:21237 UQCRB gene UQCRB Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Emory Genetics Laboratory;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex III deficiency, nuclear type 3, OMIM:615158 12709789;25446085;23454382;28604960;23281071;28275242 False 3 100;0;0 30.556 False ENSG00000156467 ENSG00000156467 HGNC:12582 UQCRB gene UQCRB Expert Review Green;Expert Review Green;NHS GMS;London North GLH;NHS GMS;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex III deficiency, nuclear type 3, OMIM:615158;Complex III (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits);Isolated complex III deficiency 25446085;28604960;12709789;23454382 False 3 50;0;50 30.556 False ENSG00000156467 ENSG00000156467 HGNC:12582 UQCRC2 gene UQCRC2 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex III deficiency, nuclear type 5, OMIM:615160 23281071;28275242;33865955 False 3 75;25;0 30.556 False ENSG00000140740 ENSG00000140740 HGNC:12586 UQCRC2 gene UQCRC2 Expert Review Green;NHS GMS;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex III deficiency, nuclear type 5, OMIM:615160 23281071;28275242;33865955 False 3 100;0;0 30.556 False ENSG00000140740 ENSG00000140740 HGNC:12586 UQCRFS1 gene UQCRFS1 Expert Review Green;NHS GMS;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex III deficiency, nuclear type 10, OMIM:618775 31883641 False 3 75;25;0 30.556 False ENSG00000169021 ENSG00000169021 HGNC:12587 UQCRFS1 gene UQCRFS1 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mitochondrial complex III deficiency, nuclear type 10, OMIM:618775 31883641 False 3 67;33;0 30.556 False ENSG00000169021 ENSG00000169021 HGNC:12587 UROC1 gene UROC1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal ?Urocanase deficiency , OMIM:276880;urocanic aciduria, MONDO:0010167 19304569;25529582;27391121;30619714;32439973 False 3 25;50;25 30.556 False ENSG00000159650 ENSG00000159650 HGNC:26444 UROD gene UROD London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Porphyria cutanea tarda (Porphyrias with erosive photodermatosis) 27604308 False 3 50;0;50 30.556 False ENSG00000126088 ENSG00000126088 HGNC:12591 UROS gene UROS London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Congenital erythropoietic porphyria (Porphyrias with erosive photodermatosis);Porphyria, congenital erythropoietic 263700 27604308 False 3 100;0;0 30.556 False ENSG00000188690 ENSG00000188690 HGNC:12592 USP18 gene USP18 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pseudo-TORCH syndrome 2, 617397 12833411;27325888;31940699 False 3 100;0;0 30.556 False ENSG00000184979 ENSG00000184979 HGNC:12616 USP7 gene USP7 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Hao-Fountain syndrome, 616863 19946331;26365382;30679821;33012787 False 3 100;0;0 30.556 False ENSG00000187555 ENSG00000187555 HGNC:12630 USP9X gene USP9X Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Mental retardation, X-linked 99 300919 XLR;Mental retardation, X-linked 99, syndromic, female-restricted 300968 24607389 False 3 100;0;0 30.556 False ENSG00000124486 ENSG00000124486 HGNC:12632 VAMP2 gene VAMP2 Expert Review;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Cortical visual impairment;Seizures;Stereotypic behavior;Generalized hypotonia;Intellectual disability;Abnormality of movement;Global developmental delay;Generalized hypotonia, Global developmental delay, Intellectual disability, Autistic behavior, Stereotypic behavior, Seizures, Abnormality of movement, Cortical visual impairment;Autistic behavior 30929742 False 3 100;0;0 30.556 False ENSG00000220205 ENSG00000220205 HGNC:12643 VARS gene VARS Expert Review Green;Expert Review;Literature;Expert Review Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal NDMSCA;Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy, 617802;# 617802. NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, SEIZURES, AND CORTICAL ATROPHY 26539891;30275004;29691655 False 3 100;0;0 30.556 False ENSG00000204394 ENSG00000204394 HGNC:12651 VARS2 gene VARS2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 20, 615917 False 3 100;0;0 30.556 False ENSG00000137411 ENSG00000137411 HGNC:21642 VARS2 gene VARS2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Combined oxidative phosphorylation deficiency 20, 615917 False 3 100;0;0 30.556 True ENSG00000137411 ENSG00000137411 HGNC:21642 VARS2 gene VARS2 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Combined oxidative phosphorylation deficiency 20, OMIM #615917 24827421;25058219;29137650;29314548;31064326 False 3 100;0;0 30.556 False ENSG00000137411 ENSG00000137411 HGNC:21642 VCP gene VCP NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 37883978 False 3 100;0;0 30.556 False ENSG00000165280 ENSG00000165280 HGNC:12666 VIPAS39 gene VIPAS39 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM:613404;ARC syndrome 27604308;22753090;26808426 False 3 100;0;0 30.556 False ENSG00000151445 ENSG00000151445 HGNC:20347 VKORC1 gene VKORC1 Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Vitamin K-dependent clotting factors, combined deficiency of, 2, OMIM:607473 27604308 False 3 100;0;0 30.556 False ENSG00000167397 ENSG00000167397 HGNC:23663 VLDLR gene VLDLR Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1, 224050;CEREBELLAR ATAXIA MENTAL RETARDATION AND DYSEQUILIBRIUM SYNDROME TYPE 1 (CMARQ1) False 3 100;0;0 30.556 False ENSG00000147852 ENSG00000147852 HGNC:12698 VPS11 gene VPS11 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 12, OMIM:616683 26307567;27120463;27473128 False 3 100;0;0 30.556 False ENSG00000160695 ENSG00000160695 HGNC:14583 VPS11 gene VPS11 Expert Review Green;Expert Review;Expert Review;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Leukodystrophy, hypomyelinating, 12, 616683;Leukodystrophy, hypomyelinating, 12 (MIM 616683) 27473128;26307567;27120463 False 3 100;0;0 30.556 False ENSG00000160695 ENSG00000160695 HGNC:14583 VPS13B gene VPS13B Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Cohen syndrome, 216550;COHEN SYNDROME False 3 100;0;0 30.556 False ENSG00000132549 ENSG00000132549 HGNC:2183 VPS16 gene VPS16 NHS GMS;Expert Review Green;Other Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mucopolysaccharidosis-like syndrome (biallelic);Dystonia Associated with Lysosomal Abnormalities (monoallelic);Dystonia 30, OMIM:619291 33938619;34013567 False 3 100;0;0 30.556 False ENSG00000215305 ENSG00000215305 HGNC:14584 VPS33A gene VPS33A NHS GMS;Expert Review Green;Other Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mucopolysaccharidosis-plus syndrome OMIM:617303;mucopolysaccharidosis-like syndrome with congenital heart defects and hematopoietic disorders MONDO:0015012 28013294;27547915;31070736 False 3 100;0;0 30.556 False ENSG00000139719 ENSG00000139719 HGNC:18179 VPS33A gene VPS33A Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Mucopolysaccharidosis-plus syndrome, OMIM:617303;mucopolysaccharidosis-plus syndrome, MONDO:0015012 27547915;28013294;31070736;39273517 False 3 100;0;0 30.556 False ENSG00000139719 ENSG00000139719 HGNC:18179 VPS33B gene VPS33B Expert Review Green;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Inherited bleeding disorders;Unexplained kidney failure in young people;CAKUT;ARC Syndrome (Other metabolic disorders);Arthrogryposis 27604308;18853461 False 3 100;0;0 30.556 False ENSG00000184056 ENSG00000184056 HGNC:12712 VPS41 gene VPS41 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Dystonia;Intellectual disability 32808683;33764426;33851776 False 3 100;0;0 30.556 False ENSG00000006715 ENSG00000006715 HGNC:12713 VPS4A gene VPS4A Expert Review Green;Research;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted CIMDAG syndrome 33186545;33186543;33460484 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000132612 ENSG00000132612 HGNC:13488 VPS53 gene VPS53 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pontocerebellar hypoplasia, type 2E, 615851;Progressive cerebello-cerebral atrophy;intellectual disability;developmental delay 24577744;2920088 False 3 0;100;0 30.556 False ENSG00000141252 ENSG00000141252 HGNC:25608 VRK1 gene VRK1 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Pontocerebellar hypoplasia type 1A, 607596;PONTOCEREBELLAR HYPOPLASIA TYPE 1 False 3 100;0;0 30.556 False ENSG00000100749 ENSG00000100749 HGNC:12718 WAC gene WAC Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Paper out in august 0 False 3 100;0;0 30.556 False ENSG00000095787 ENSG00000095787 HGNC:17327 WARS gene WARS Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities, OMIM:620317;neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities, MONDO:0957218 34585293;35790048;35815345 False 3 100;0;0 30.556 False ENSG00000140105 ENSG00000140105 HGNC:12729 WARS2 gene WARS2 Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, 617710 28905505;28650581;28236339 False 3 50;50;0 30.556 False ENSG00000116874 ENSG00000116874 HGNC:12730 WARS2 gene WARS2 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, OMIM:617710 31282308;28650581;30920170 False 3 100;0;0 30.556 False ENSG00000116874 ENSG00000116874 HGNC:12730 WARS2 gene WARS2 Expert Review Green;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, 617710 28650581;28905505;28236339 False 3 50;50;0 30.556 False ENSG00000116874 ENSG00000116874 HGNC:12730 WARS2 gene WARS2 Expert Review;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, 617710 29783990;28236339;29120065;28650581;28905505 False 3 100;0;0 30.556 False ENSG00000116874 ENSG00000116874 HGNC:12730 WASF1 gene WASF1 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental disorder with absent language and variable seizures, 618707;ID associated with autistic features, seizures, and developmental delay;intellectual disability 29961568 False 3 100;0;0 30.556 False ENSG00000112290 ENSG00000112290 HGNC:12732 WBP4 gene WBP4 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopemental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities, OMIM:620852;neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities, MONDO:0971043 37963460 False 3 100;0;0 30.556 False ENSG00000120688 ENSG00000120688 HGNC:12739 WDFY3 gene WDFY3 Expert Review Green;Victorian Clinical Genetics Services;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Microcephaly 18, primary, autosomal dominant, 617520 27008544;31327001;25198012;28191889 False 3 100;0;0 30.556 False ENSG00000163625 ENSG00000163625 HGNC:20751 WDPCP gene WDPCP Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal BARDET-BIEDL SYNDROME TYPE 15 (BBS15) 0 False 3 33;67;0 30.556 False ENSG00000143951 ENSG00000143951 HGNC:28027 WDR26 gene WDR26 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Skraban-Deardorff syndrome;617616;intellectual disability 28686853;28921851 False 3 100;0;0 30.556 False ENSG00000162923 ENSG00000162923 HGNC:21208 WDR37 gene WDR37 Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurooculocardiogenitourinary syndrome, OMIM:618652 31327510;31327508 False 3 100;0;0 30.556 False Other ENSG00000047056 ENSG00000047056 HGNC:31406 WDR4 gene WDR4 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Galloway-Mowat syndrome 6, OMIM:61834;Microcephaly, growth deficiency, seizures, and brain malformations, OMIM:618347 29597095;26416026;28617965;30079490 False 3 100;0;0 30.556 False ENSG00000160193 ENSG00000160193 HGNC:12756 WDR45 gene WDR45 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Neurodegeneration with brain iron accumulation 5 27604308 False 3 0;0;0 30.556 False ENSG00000196998 ENSG00000196998 HGNC:28912 WDR45 gene WDR45 Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Neurodegeneration with brain iron accululation 5, 300894;NEURODEGENERATION WITH BRAIN IRON ACCUMULATION (NBIA) False 3 100;0;0 30.556 False ENSG00000196998 ENSG00000196998 HGNC:28912 WDR45B gene WDR45B Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, OMIM:617977 21937992;28503735;27431290 False 3 0;0;100 30.556 False ENSG00000141580 ENSG00000141580 HGNC:25072 WDR47 gene WDR47 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 39609633 False 3 100;0;0 30.556 False ENSG00000085433 ENSG00000085433 HGNC:29141 WDR5 gene WDR5 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted neurodevelopmental disorder, MONDO:0700092;intellectual disability, MONDO:0001071 36408368 False 3 100;0;0 30.556 False Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments ENSG00000196363 ENSG00000196363 HGNC:12757 WDR62 gene WDR62 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, OMIM:604317 20890278;20729831;21834044;10573015;20890279;30500859 False 3 100;0;0 30.556 False ENSG00000075702 ENSG00000075702 HGNC:24502 WDR73 gene WDR73 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal GALLOWAY-MOWAT SYNDROME: MICROCEPHALY AND STEROID-RESISTANT NEPHROTIC SYNDROME;Galloway-Mowat syndrome 1, 251300 25466283 False 3 33;67;0 30.556 False ENSG00000177082 ENSG00000177082 HGNC:25928 WDR81 gene WDR81 Expert Review Green;Victorian Clinical Genetics Services;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal cerebellar ataxia, intellectual disability and quadrupedal locomotion;Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2, 610185 28972664; 21885617; 26437881; 28961333 False 3 25;0;75 30.556 False ENSG00000167716 ENSG00000167716 HGNC:26600 WDR83OS gene WDR83OS Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Neurodevelopmental disorder with variable familial hypercholanemia, OMIM:621016 30250217;39471804 False 3 75;0;25 30.556 False ENSG00000105583 ENSG00000105583 HGNC:30203 WFS1 gene WFS1 Expert Review Green;NHS GMS;London North GLH;NHS GMS Childhood onset leukodystrophy Neurology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Wolfram syndrome 1, OMIM:222300;Wolfram-like syndrome, autosomal dominant, OMIM:614296;Diabetes mellitus, noninsulin-dependent, association with, OMIM:125853 27604308;30171196;33693650 False 3 50;0;50 30.556 False ENSG00000109501 ENSG00000109501 HGNC:12762 WIPI2 gene WIPI2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual developmental disorder with short stature and variable skeletal anomalies, OMIM:618453 30968111;34557665 False 3 100;0;0 30.556 False ENSG00000157954 ENSG00000157954 HGNC:32225 WNK3 gene WNK3 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Prieto syndrome, OMIM:309610;Intellectual disability, MONDO:0001071 26350204;35678782 False 3 25;0;75 30.556 False ENSG00000196632 ENSG00000196632 HGNC:14543 WNT1 gene WNT1 Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Osteogenesis imperfecta, type XV, 615220;{Osteoporosis, early-onset, susceptibility to, autosomal dominant}, 615221 False 3 100;0;0 30.556 False ENSG00000125084 ENSG00000125084 HGNC:12774 WWOX gene WWOX Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 12 24456803 False 3 33;67;0 30.556 False ENSG00000186153 ENSG00000186153 HGNC:12799 XDH gene XDH London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Xanthinuria type II (Disorders of purine metabolism);Xanthinuria type I (Disorders of purine metabolism) 27604308 False 3 100;0;0 30.556 False ENSG00000158125 ENSG00000158125 HGNC:12805 XPA gene XPA Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Xeroderma pigmentosum, group A, 278700 27603812;27413738;26302748;26743599 False 3 0;0;0 30.556 False ENSG00000136936 ENSG00000136936 HGNC:12814 XPC gene XPC Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Xeroderma pigmentosum, group C, 278720 27413738 False 3 0;0;0 30.556 False ENSG00000154767 ENSG00000154767 HGNC:12816 XPNPEP3 gene XPNPEP3 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Nephronophthisis-like nephropathy 1 OMIM:613159;nephronophthisis-like nephropathy 1 MONDO:0013163 20179356;32660933 False 3 100;0;0 30.556 False ENSG00000196236 ENSG00000196236 HGNC:28052 XPR1 gene XPR1 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Basal ganglia calcification, idiopathic, 6, 616413;Basal ganglia calcification (Fahr syndrome) 27230854 - report of a novel variant in a 41-year old man complaining of micrographia and dysarthria and demonstrating mild parkinsonism, cerebellar ataxia and executive dysfunction;25938945 False 3 0;0;0 30.556 False ENSG00000143324 ENSG00000143324 HGNC:12827 XRCC4 gene XRCC4 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Short stature, microcephaly, and endocrine dysfunction, OMIM:616541 25728776 False 3 33;67;0 30.556 False ENSG00000152422 ENSG00000152422 HGNC:12831 XYLT1 gene XYLT1 Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Desbuquois dysplasia 2, OMIM:615777;Desbuquois dysplasia 2, MONDO:0014343 23982343;24581741;22711505;30554721 False 3 100;0;0 30.556 False ENSG00000103489 ENSG00000103489 HGNC:15516 XYLT1 gene XYLT1 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Desbuquois dysplasia 2, OMIM:615777;Desbuquois dysplasia 2, MONDO:0014343 23982343;24581741;22711505;30554721 False 3 100;0;0 30.556 False ENSG00000103489 ENSG00000103489 HGNC:15516 XYLT2 gene XYLT2 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spondyloocular syndrome 26987875;26027496 False 3 0;0;0 30.556 False ENSG00000015532 ENSG00000015532 HGNC:15517 YARS2 gene YARS2 London North GLH;NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Myopathy, lactic acidosis, and sideroblastic anemia 2, 613561 27604308 False 3 100;0;0 30.556 False ENSG00000139131 ENSG00000139131 HGNC:24249 YARS2 gene YARS2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Expert list;Expert Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Myopathy, lactic acidosis, and sideroblastic anemia 2, 613561 False 3 100;0;0 30.556 False ENSG00000139131 ENSG00000139131 HGNC:24249 YIF1B gene YIF1B Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Kaya-Barakat-Masson syndrome, OMIM:619125 32006098 False 3 100;0;0 30.556 False ENSG00000167645 ENSG00000167645 HGNC:30511 YIPF5 gene YIPF5 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly, epilepsy, and diabetes syndrome 2, OMIM:619278 33164986 False 3 100;0;0 30.556 False ENSG00000145817 ENSG00000145817 HGNC:24877 YWHAG gene YWHAG Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Epileptic encephalopathy, early infantile 56, 617665;Intellectual disability 28777935;28135719;25363760;26297819;27288018 False 3 0;100;0 30.556 False ENSG00000170027 ENSG00000170027 HGNC:12852 YY1 gene YY1 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted "Gabriele-de Vries syndrome 617557" 21076407;28575647 False 3 100;0;0 30.556 False ENSG00000100811 ENSG00000100811 HGNC:12856 ZBTB18 gene ZBTB18 Expert Review Green;Victorian Clinical Genetics Services Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown intellectual disability with variable features; global developmental delay; Mental retardation, autosomal dominant 22, 612337 28345786;27598823;24193349;23020937;26740508;25529582 False 3 50;0;50 30.556 False ENSG00000179456 ENSG00000179456 HGNC:13030 ZBTB20 gene ZBTB20 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted PRIMROSE SYNDROME 25017102 False 3 33;67;0 30.556 False ENSG00000181722 ENSG00000181722 HGNC:13503 ZBTB24 gene ZBTB24 Victorian Clinical Genetics Services;Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Immunodeficiency-centromeric instability-facial anomalies syndrome 2, 614069;intellectual disability 21596365;22786748;23486536 False 3 100;0;0 30.556 False ENSG00000112365 ENSG00000112365 HGNC:21143 ZBTB47 gene ZBTB47 NHS GMS;Expert Review Green;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Neurodevelopmental disorder, MONDO;0700092 37743782 False 3 100;0;0 30.556 False ENSG00000114853 ENSG00000114853 HGNC:26955 ZBTB7A gene ZBTB7A Expert Review Green;NHS GMS;Other;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin, OMIM:619769 31645653;34515416 False 3 75;25;0 30.556 False ENSG00000178951 ENSG00000178951 HGNC:18078 ZC4H2 gene ZC4H2 NHS GMS;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Wieacker-Wolff syndrome, OMIM:314580;Wieacker-Wolff syndrome, female-restricted, OMIM:301041 23623388;1915520;4039531 False 3 100;0;0 30.556 False ENSG00000126970 ENSG00000126970 HGNC:24931 ZDHHC9 gene ZDHHC9 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental retardation, X-linked syndromic, Raymond type, OMIM:300799 False 3 100;0;0 30.556 False ENSG00000188706 ENSG00000188706 HGNC:18475 ZEB2 gene ZEB2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Mowat-Wilson syndrome, 235730;MOWAT-WILSON SYNDROME (MWIS) False 3 100;0;0 30.556 False ENSG00000169554 ENSG00000169554 HGNC:14881 ZFHX3 gene ZFHX3 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown syndromic intellectual disability 38412861;38035881;37292950 False 3 100;0;0 30.556 False ENSG00000140836 ENSG00000140836 HGNC:777 ZFHX4 gene ZFHX4 Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Developmental disorders;intellectual disability, dysmorphic features 26350204;21802062;33057194;24038936;39148819 False 3 25;0;75 30.556 False ENSG00000091656 ENSG00000091656 HGNC:30939 ZFX gene ZFX Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Intellectual developmental disorder, X-linked syndromic 37, OMIM:301118 26350204;26740508;38325380 False 3 50;0;50 30.556 False ENSG00000005889 ENSG00000005889 HGNC:12869 ZFYVE26 gene ZFYVE26 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 15, autosomal recessive, OMIM:270700 19805727;17661097;18098276;11342696 False 3 100;0;0 30.556 False ENSG00000072121 ENSG00000072121 HGNC:20761 ZFYVE26 gene ZFYVE26 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Spastic paraplegia 15, autosomal recessive, OMIM:270700 19084844 False 3 100;0;0 30.556 False ENSG00000072121 ENSG00000072121 HGNC:20761 ZIC1 gene ZIC1 Expert Review Green;BRIDGE study SPEED NEURO Tier1 Gene Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Structural brain anomalies with impaired intellectual development and craniosynostosis, 618736;?Craniosynostosis 6, 616602 26340333;30391508 False 3 100;0;0 30.556 False Other - please provide details in the comments ENSG00000152977 ENSG00000152977 HGNC:12872 ZIC2 gene ZIC2 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Holoprosencephaly-5, 609637;HOLOPROSENCEPHALY False 3 100;0;0 30.556 False ENSG00000043355 ENSG00000043355 HGNC:12873 ZMIZ1 gene ZMIZ1 Expert Review;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Abnormality of head or neck;Microcephaly;Abnormality of the cardiovascular system;Abnormality of the skeletal system;Feeding difficulties;Intellectual disability;Global developmental delay;Abnormality of the urinary system;Growth abnormality;Global developmental delay, Intellectual disability, Feeding difficulties, Growth abnormality, Microcephaly, Abnormality of the skeletal system, Abnormality of the urinary system, Abnormality of the cardiovascular system, Abnormality of head or neck 29754769;18053775;17967885;30639322;26163108;27479843 False 3 100;0;0 30.556 False ENSG00000108175 ENSG00000108175 HGNC:16493 ZMYM2 gene ZMYM2 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities, OMIM:619522 32891193 False 3 75;25;0 30.556 False ENSG00000121741 ENSG00000121741 HGNC:12989 ZMYM3 gene ZMYM3 Expert Review Green;NHS GMS Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Intellectual developmental disorder, X-linked 112, OMIM:301111 26350204;24721225;8817323;36586412 False 3 40;0;60 30.556 False ENSG00000147130 ENSG00000147130 HGNC:13054 ZMYND11 gene ZMYND11 Victorian Clinical Genetics Services;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted INTELLECTUAL DISABILITY 25217958;25281490 False 3 100;0;0 30.556 False ENSG00000015171 ENSG00000015171 HGNC:16966 ZMYND8 gene ZMYND8 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Delayed speech and language development;Motor delay;Intellectual disability;Abnormality of cardiovascular system morphology;Hearing abnormality;Abnormality of vision;Abnormality of the face;Seizures 35916866;32530565 False 3 100;0;0 30.556 False ENSG00000101040 ENSG00000101040 HGNC:9397 ZNF142 gene ZNF142 Expert Review;Expert Review Green;Expert Review Green;Expert Review;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Seizures;Dystonia;Intellectual disability;Global developmental delay;Tremor;Neurodevelopmental disorder with impaired speech and hyperkinetic movements, 618425 31036918 False 3 100;0;0 30.556 False ENSG00000115568 ENSG00000115568 HGNC:12927 ZNF292 gene ZNF292 Expert Review Green;NHS GMS;Literature;Radboud University Medical Center, Nijmegen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual developmental disorder, autosomal dominant 64, OMIM:619188;intellectual developmental disorder, autosomal dominant 64, MONDO:0030934 31723249;29904178 False 3 100;0;0 30.556 False ENSG00000188994 ENSG00000188994 HGNC:18410 ZNF335 gene ZNF335 NHS GMS;Expert Review Green;Other Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Microcephaly 10, primary, autosomal recessive, 615095 23178126;27540107;29652087;30500859;31187448 False 3 67;33;0 30.556 False ENSG00000198026 ENSG00000198026 HGNC:15807 ZNF462 gene ZNF462 Expert Review;Expert Review Green;Expert Review Green;Expert Review;Radboud University Medical Center, Nijmegen;Literature Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Prominent metopic ridge;Ptosis;Ptosis, Prominent metopic ridge, Craniosynostosis, Global developmental delay, Intellectual disability, Autistic behavior;Intellectual disability;Global developmental delay;Craniosynostosis;Autistic behavior 28513610;12825074;29427787;14564155 False 3 0;100;0 30.556 False ENSG00000148143 ENSG00000148143 HGNC:21684 ZNF526 gene ZNF526 Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Intellectual disability;Microcephaly;Cataracts;Epilepsy;Hypertonia;Dystonia 21937992;25558065;33397746 False 3 25;0;75 30.556 False ENSG00000167625 ENSG00000167625 HGNC:29415 ZNF699 gene ZNF699 Expert Review Green;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal DEGCAGS syndrome, OMIM:619488 33875846 False 3 100;0;0 30.556 False ENSG00000196110 ENSG00000196110 HGNC:24750 ZNF711 gene ZNF711 Victorian Clinical Genetics Services;Expert Review Green;Radboud University Medical Center, Nijmegen;Emory Genetics Laboratory;Illumina TruGenome Clinical Sequencing Services Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Mental Retardation, X-linked;Mental retardation, X-linked 97, 300803;MENTAL RETARDATION X-LINKED ZNF711-RELATED (MRXZ) False 3 100;0;0 30.556 False ENSG00000147180 ENSG00000147180 HGNC:13128 ZNFX1 gene ZNFX1 Expert Review Green;NHS GMS;Literature Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Immunodeficiency 91 and hyperinflammation, OMIM:619644;immunodeficiency 91 and hyperinflammation, MONDO:0030491 33876776;33872655 False 3 100;0;0 30.556 False ENSG00000124201 ENSG00000124201 HGNC:29271 ZSWIM6 gene ZSWIM6 Expert Review Green;Other Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Acromelic frontonasal dysostosis, 603671;Includes mental retardation;acromelic frontonasal dysostosis with severe intellectual disability 25105228;26706854 False 3 0;100;0 30.556 False ENSG00000130449 ENSG00000130449 HGNC:29316 DMPK_CTG str DMPK NHS GMS;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Myotonic dystrophy 1, OMIM:160900 False 3 100;0;0 30.556 False ENSG00000104936 ENSG00000104936 HGNC:2933 19 46273463 46273522 45770205 45770264 CTG 35 50 DMPK_CTG str DMPK Expert Review Green;NHS GMS;Expert Review Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Myotonic dystrophy 1, OMIM:160900 False 3 0;0;0 30.556 True ENSG00000104936 ENSG00000104936 HGNC:2933 19 46273463 46273522 45770205 45770264 CTG 35 50 DMPK_CTG str DMPK Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Myotonic dystrophy 1, OMIM:160900 False 3 0;0;0 30.556 True ENSG00000104936 ENSG00000104936 HGNC:2933 19 46273463 46273522 45770205 45770264 CTG 35 50 FMR1_CGG str FMR1 Expert Review Green;NHS GMS;Expert list Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Fragile X syndrome, OMIM:300624;Fragile X tremor/ataxia syndrome, OMIM:300623 False 3 0;0;0 30.556 False ENSG00000102081 ENSG00000102081 HGNC:3775 X 146993569 146993628 147912051 147912110 CGG 55 200 FXN_GAA str FXN NHS GMS;Expert Review Green;Expert list Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal Friedreich ataxia OMIM:229300;Friedreich ataxia with retained reflexes OMIM:229300;Friedreich ataxia 1 MONDO:0100340 False 3 100;0;0 30.556 False ENSG00000165060 ENSG00000165060 HGNC:3951 9 71652203 71652220 69037287 69037304 GAA 44 66 ISCA-37390-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown 123450;PMID 15635506: characteristic cry, speech delay, facial dysmorphology, and level of mental retardation. PMID 11238681: interstitial deletions and one with a small terminal deletion confirmed the existence of two critical regions, one for dysmorphism and mental retardation in p15.2 and the other for the cat cry in p15.3. Results from one patient permitted the cat cry region to be distally narrowed from D5S13 to D5S731, study supports hypothesis of a separate region in p15.3 for the speech delay 11238681;15635506 False 3 0;0;0 30.556 False 5 37695 11347150 3 60 cnv_loss 5p15 terminal (Cri du chat syndrome) region Loss ISCA-37392-Gain region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown intellectual disability;609757;behavior problems;abnormal gait and station;cardiovascular disease;phonologic disorders;distinctive facial features;neurologic abnormalities;speech sound disorders 26610320 False 3 0;0;0 30.556 False 7 73330452 74728172 3 60 cnv_gain 7q11.23 recurrent (Williams-Beuren syndrome) region (includes ELN) Gain ISCA-37392-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown 194050;Williams syndrome 20301427 False 3 0;0;0 30.556 False 7 73330452 74728172 3 60 cnv_loss 7q11.23 recurrent (Williams-Beuren syndrome) region (includes ELN) Loss ISCA-37393-Gain region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown PMID 22890013: variable phenotype including developmental delay, ocular coloboma, preauricular tags/pits, cleft palate, skeletal defects, heart defects, urogenital defect, anal defect, hearing loss, clinodactyly of fifth fingers, umbilical hernia, accessory spleen, strabismus, shortening of the fifth finger. PMID 22495764: Inter and intra individual variability of phenotype, mosaic. PMID 11693792: preauricular skin tags and pits, downslanting palpebral fissures, hypertelorism, ectopic anus, hypospadias, and hypoplastic left heart syndrome;115470 11693792;22890013;22495764 False 3 0;0;0 30.556 False 22 16912063 18109094 3 60 cnv_gain 22q11.21 recurrent (Cat eye syndrome) region (includes CECR2) Gain ISCA-37394-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown 2q37 deletion syndrome is a condition that can affect many parts of the body. This condition is characterized by weak muscle tone (hypotonia) in infancy, mild to severe intellectual disability and developmental delay, behavioral problems, characteristic facial features, and other physical abnormalities. PMID 23188045 brachydactyly-mental retardation syndrome, Albright hereditary osteodystrophy-like syndrome, developmental delay and behavioural abnormalities in combination;600430 25402011;23188045 False 3 100;0;0 30.556 False 2 239032997 241988449 3 60 cnv_loss 2q37.3 terminal region (includes HDAC4) Loss ISCA-37396-Loss region Expert Review Green;Expert list Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Chromosome 15q24 deletion syndrome, 613406;PMID: 22180641 intellectual disability, growth retardation, unusual facial morphology;developmental delay, severe speech problems;PMID:19557438 Developmental delay, short stature, hypotonia, digital abnormalities, joint laxity, genital abnormalities, characteristic facial features;PMID:614294 Developmental delay, loose connective tissue, digital and genital anomalies, distinct facial gestalt, congenital diaphragmatic hernia 22180641;19557438;19233321 False 3 100;0;0 30.556 True 15 72671374 75680568 3 60 cnv_loss 15q24 recurrent region (A-D) (includes SIN3A) Loss ISCA-37397-Gain region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown seizures;failure to thrive;ADHD;heart defects;speech disturbances;hypernasal speech;hearing impariment;abnormal behaviour;developmental delay;hypotonia;micro- or macrocephaly 18414210;22140377;19193630 False 3 0;0;0 30.556 False 22 21562828 23306924 3 60 cnv_gain 22q11.2 recurrent region (distal region, LCR22-D to LCR22-E or -F) Gain ISCA-37397-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown diaphragmatic hernia;mild skeletal abnormalities;uterine didelphys;611867;DiGeorge syndrome (DGS);clinodactyly;velocardiofacial syndrome;ADHD;Goldenhar syndrome;prematurity;developmental delay;micropephaly;cardiovascular defects;Seizures;global developmental delay;language delay;prenatal and postnatal growth delay;Hyptonia 21671380;23765049;18179902 False 3 0;0;0 30.556 False 22 21562828 23306924 3 60 cnv_loss 22q11.2 recurrent region (distal region, LCR22-D to LCR22-E or -F) Loss ISCA-37400-Gain region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown 614671;intellectual disability;delayed development;autism;specific deficits in speech or language 21841781;18184952;21731881 False 3 0;0;0 30.556 False 16 29638676 30188531 3 60 cnv_gain 16p11.2 recurrent region (includes TBX6) (proximal region) (BP4-BP5) Gain ISCA-37400-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown seizures;intellectual disability;Chiari malformations;cerebellar ectopia;611913;mental retardation;Macrocephaly;developmental delay;autism spectrum disorder (ASD);vertebral anomalies 21841781;18184952;20301775 False 3 0;0;0 30.556 False 16 29638676 30188531 3 60 cnv_loss 16p11.2 recurrent region (includes TBX6) (proximal region) (BP4-BP5) Loss ISCA-37401-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Wilms tumor, aniridia, genitourinary anomalies and mental retardation syndrome;194072 False 3 0;0;0 30.556 False 11 31781961 32489442 3 60 cnv_loss 11p13 (WAGR syndrome) region Loss ISCA-37405-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal juvenile nephronophthisis 1: including growth retardation. Joubert syndrome: multisystem disease characterized by cerebellar vermis hypoplasia with prominent superior cerebellar peduncles (resulting in the 'molar tooth sign,' or MTS, on axial MRI), mental retardation, hypotonia, irregular breathing pattern, and eye movement abnormalities;266900;609583 9856524;15138899;8852662 False 3 0;0;0 30.556 False 2 110104531 110228181 30 60 cnv_loss 2q13 recurrent region (includes NPHP1) Loss ISCA-37406-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown PMID: 10573006 death in infancy, accessory spleens, hypoplastic left heart, abnormal pulmonary lobulation, renal agenesis (patient 1), severe neonatal seizures (patient 2). PMID 16783566: failure to thrive, life-threatening malformations, and/or critical infections, and all died in infancy (5 weeks, 7 months, and 9 months, respectivelyFrom Genetics Home Reference: short stature, moderate to severe intellectual disability, distinctive facial features, and broad thumbs and first toes;610543 10573006;16783566 False 3 0;0;0 30.556 False 16 3725055 3880120 3 60 cnv_loss 16p13.3 region (includes CREBBP) Loss ISCA-37408-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Dysmorphic features, moderate to severe intellectual disability, microcephaly and renal anomalies 16963482;22579565;18245392 False 3 0;0;0 30.556 False 2 58912065 62261736 3 60 cnv_loss 2p15p16.1 region (includes BCL11A) Loss ISCA-37411-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown PMID: 19289393 incomplete penetrance for developmental delay, mental retardation, or borderline IQ in most and autistic spectrum disorder (6/14), speech delay, aggressiveness, attention deficit hyperactivity disorder, and other behavioural problems;612001;PMID: 18278044 mental retardation, epilepsy and variable facial and digital dysmorphisms;PMID: 19136953 idiopathic generalized epilepsy without other features previously associated with 15q13.3 microdeletions, such as intellectual disability, autism or schizophrenia 19289393;19136953;18278044 False 3 0;0;0 30.556 False 15 30900686 32153204 3 60 cnv_loss 15q13.3 recurrent region (BP4-BP5) (includes CHRNA7) Loss ISCA-37415-Gain region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Intellectual disability;Developmental delay;Autism;Aortopathy 23637818;24352232;21614007;30287593 False 3 100;0;0 30.556 False 16 15417854 16198408 2 60 cnv_gain 16p13.11 recurrent region (includes MYH11) Gain ISCA-37415-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown PMID: 18550696 Phenotypic variability, common features were identified: mental retardation, microcephaly and epilepsy in three patients, two of these had also short stature, and two other deletion carriers ascertained prenatally presented with cleft lip and midline defects 19843651;18550696;24246141 False 3 0;0;0 30.556 False 16 15417854 16198408 3 60 cnv_loss 16p13.11 recurrent region (includes MYH11) Loss ISCA-37418-Gain region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown infantile hypotonia, failure to thrive, mental retardation, autistic features, sleep apnea, and structural cardiovascular anomalies;610883;characterized by hypotonia, poor feeding, failure to thrive, developmental delay, mild-moderate intellectual deficit, and neuropsychiatric disorders. Structural cardiovascular anomalies (dilated aortic root, bicommissural aortic valve, atrial/ventricular and septal defects) and sleep disturbance (obstructive and central sleep apnea) are also frequently associated False 3 0;0;0 30.556 False 17 16906714 20309889 3 60 cnv_gain 17p11.2 recurrent (SMS/PLS) region (includes RAI1) Gain ISCA-37418-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Smith-Magenis syndrome, OMIM:182290;Smith-Magenis syndrome, MONDO:0008434 False 3 100;0;0 30.556 False 17 16906714 20309889 3 60 cnv_loss 17p11.2 recurrent (SMS/PLS) region (includes RAI1) Loss ISCA-37420-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Koolen-De Vries syndrome, OMIM:610443;Developmental delay/intellectual disability, hypotonia, distinctive facial features, congenital malformations, and behavioural feature 25217958;18628315 False 3 0;0;0 30.556 False 17 45627800 46087514 3 60 cnv_loss 17q21.3 recurrent region (includes KANSL1) Loss ISCA-37421-Gain region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Chromosome 1q21.1 duplication syndrome;ncomplete penetrance and variable expression characterized by macrocephaly, developmental delay, intellectual disability, psychiatric disturbances (autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, mood disorders) and mild facial dysmorphism (high forehead, hypertelorism). Other associated features include congenital heart defects, hypotonia, short stature, scoliosis;612475;1q21.1 microduplication syndrome 3298277;3817079 False 3 0;0;0 30.556 False 1 147105904 147917509 3 60 cnv_gain 1q21.1 recurrent region (BP3-BP4, distal) (includes GJA5) Gain ISCA-37421-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown dysmorphic features;612474;Moderate mental retardation, microcephaly, cardiac abnormalities, and cataracts;mild to moderate developmental delay False 3 0;0;0 30.556 False 1 147105904 147917509 3 60 cnv_loss 1q21.1 recurrent region (BP3-BP4, distal) (includes GJA5) Loss ISCA-37423-Gain region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Behavioral problems, cleft lip and/or palate, macrocephaly, and seizures were confirmed as additional features among the new patients, and novel features included neonatal respiratory distress, attention deficit hyperactivity disorder (ADHD), ocular anomalies, balance problems, hypotonia, and hydrocele.;mild to moderate developmental delay, intellectual disability, mild facial dysmorphism (incl. prominent forehead, arched eyebrows, broad nasal bridge, upturned nares, cleft lip and/or palate) and congenital cardiac anomalies (e.g., atrioventricular septal defect). Other reported features include macrocephaly, behavioral abnormalities (e.g., attention deficit disorder), seizures, hypotonia and ocular and digital anomalies (poly/syndactyly);congenital heart disease;8p23.1 duplication syndrome 21933911;23345203 False 3 100;0;0 30.556 False 8 8242542 11908820 2 60 cnv_gain 8p23.1 recurrent region (includes GATA4) Gain ISCA-37423-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown prenatal and postnatal growth retardation, low birth weight, mild to moderate intellectual deficit, psychomotor retardation, poor speech, seizures, behavioral problems such as hyperactivity and impulsiveness. Frequent craniofacial abnormalities include microcephaly, high and narrow forehead, broad nasal bridge, epicanthic folds, high arched palate, short neck and low set unusually shaped ears. Furthermore congenital heart defects (atrioventricular, septal defects, pulmonary stenosis), congenital diaphragmatic hernia and in boys cryptorchidism and hypospadias have been frequently reported.;congenital heart defects, microcephaly, psychomotor delay and behavioural problems;hyperactivity, craniofacial abnormalities;8p23.1 microdeletion syndrome;moderate intellectual disability 23239632;20969981 False 3 100;0;0 30.556 False 8 8242542 11908820 3 60 cnv_loss 8p23.1 recurrent region (includes GATA4) Loss ISCA-37424-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown PMID 20345475 macrocephaly, hypertelorism, and arachnodactyly, and neurodevelopmental delay that includes failure to thrive, hypotonia, and feeding difficulties in the neonatal period, and receptive and expressive language delay with global neurodevelopmental delay after the neonatal period. PMID: 21248748 developmental delay, mainly affecting speech. In addition, macrocephaly, mild facial dysmorphisms, cerebellar anomalies, cardiac defects and congenital breast aplasia;PMID: 25217958 none specified;PMID: 24550761 age-appropriate language development evaluated by a standardized test at an age of 2 years and 3 months. The boy was born with a cleft palate - a feature not present in any of the patients described before, phenotype of patients with an LCR3/4-flanked 10q22.3q23.2 deletion can be rather variable 25217958;20345475;21248748;24550761 False 3 0;0;0 30.556 False 10 79923087 86979631 3 60 cnv_loss 10q22.3q23.2 recurrent region (LCR-3/4-flanked) (includes BMPR1A) Loss ISCA-37425-Gain region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Microcephaly, short stature and developmental delay;short stature, microcephaly, learning disability or mild to moderate ID, and distinctive facial features comprising periorbital fullness, short palpebral fissures, a long nose with broad or long nasal tip, a smooth philtrum and a thin upper lip vermilion. Behavioral problems, ocular and minor hand anomalies may be associated. 23913520;23599694 False 3 0;0;0 30.556 False 5 176301976 177620792 3 60 cnv_gain 5q35 recurrent (Sotos syndrome) region (includes NSD1) Gain ISCA-37425-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown macrocephaly, overgrowth and advanced bone age;colpocephaly;Sotos syndrome;macrocephaly;117550;rapid growth, acromegalic features, and a nonprogressive cerebral disorder with mental retardation. High-arched palate and prominent jaw False 3 0;0;0 30.556 False 5 176301976 177620792 3 60 cnv_loss 5q35 recurrent (Sotos syndrome) region (includes NSD1) Loss ISCA-37429-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Wolf-Hirschhorn syndrome, OMIM:194190 20026556;14630905 False 3 0;0;0 30.556 False 4 337779 2009235 3 60 cnv_loss 4p16.3 terminal (Wolf-Hirshhorn syndrome) region Loss ISCA-37430-Gain region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown 613215;Chromosome 17p13.3 duplication syndrome;variable psychomotor delay and dysmorphic features;17q11.2 microduplication syndrome 23813913;19520700;19136950 False 3 0;0;0 30.556 False 17 1344539 2685615 3 60 cnv_gain 17p13.3 (Miller-Dieker syndrome) region (includes YWHAE and PAFAH1B1) Gain ISCA-37430-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown microcephaly, dysgenesis of the corpus callosum, and cerebellar atrophy, as well as neurobehavioral disorders, including delayed development, mental retardation, and attention deficit-hyperactivity disorder. Patients with duplications of YWHAE tended to have macrosomia, facial dysmorphism, and mild developmental delay;growth restriction, craniofacial dysmorphisms, structural abnormalities of brain and cognitive impairment;Chromosome 17p13.3 duplication syndrome;prominent forehead, bitemporal hollowing, short nose with upturned nares, protuberant upper lip, thin vermilion border, and small jaw;Characteristic facies, pre- and post-natal growth retardation;247200;classic lissencephaly (pachygyria, incomplete or absent gyration of the cerebrum), microcephaly, wrinkled skin over the glabella and frontal suture, prominent occiput, narrow forehead, downward slanting palpebral fissures, small nose and chin, cardiac malformations, hypoplastic male extrenal genitalia, growth retardation, and mental deficiency with seizures and EEG abnormalities;Miller-Dieker lissencephaly syndrome False 3 0;0;0 30.556 False 17 1344539 2685615 3 60 cnv_loss 17p13.3 (Miller-Dieker syndrome) region (includes YWHAE and PAFAH1B1) Loss ISCA-37431-Gain region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown early onset of baldness (15 years old), dental enamel hypoplasia and minor facial dysmorphism;Chromosome 17q11.2 deletion syndrome, 1.4Mb;DD/ID, facial dysmorphisms, and seizures 25205021;22241097;18183042 False 3 0;0;0 30.556 False 17 30780079 31937008 2 60 cnv_gain 17q11.2 recurrent region (includes NF1) Gain ISCA-37431-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown dysmorphic features, cardiac anomalies and mental retardation;613675;variable facial dysmorphism, cafe-au-lait spots, neurofibromas and Lisch nodules in the iris, mental retardation, developmental delay, an excessive number of early-onset neurofibromas and an increased risk for malignant peripheral nerve sheath tumors;NEUROFIBROMATOSIS 1 MICRODELETION SYNDROME;NF1 MICRODELETION SYNDROME;Chromosome 17q11.2 deletion syndrome, 1.4Mb False 3 0;0;0 30.556 False 17 30780079 31937008 3 60 cnv_loss 17q11.2 recurrent region (includes NF1) Loss ISCA-37432-Gain region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown developmental delay, mild to severe intellectual disability, speech delay, seizures, microcephaly, behavioral abnormalities, autism spectrum disorder, eye or vision defects (such as strabismus, astigmatism, amblyopia, cataract, coloboma, and microphthalmia), non-specific dysmorphic features, hypotonia, cardiac and renal anomalies, schizophrenia;Speech and language delay;Seizures (not all);Chromosome 17q12 duplication syndrome;614526;Behavioural difficulties False 3 0;0;0 30.556 False 17 36458167 37854616 3 60 cnv_gain 17q12 recurrent (RCAD syndrome) region (includes HNF1B) Gain ISCA-37432-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown RCAD syndrome;utero-vaginal atresia;Schizophrenia;614527;delayed development, intellectual disability;Renal cysts and diabetes syndrome;Autism Spectrum Disorder;Mayer-Rokitansky-Kster-Hauser (MRKH) syndrome in females;Chromosome 17q12 deletion syndrome;global developmental delay False 3 0;0;0 30.556 False 17 36458167 37854616 3 60 cnv_loss 17q12 recurrent (RCAD syndrome) region (includes HNF1B) Loss ISCA-37434-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown posteriorly rotated, low-set, abnormal ears;brachycephaly;epicanthus;heart defects;pointed chin;deep-set eyes;microcephaly;hypotonia;seizures;poor/absent speech;central nervous system anomalies;large anterior fontanels;microbrachycephaly;mental retardation;growth impairment;large, late-closing anterior fontanel;flat nose;nasal bridge;developmental delay;hearing impairment;distinct dysmorphic features;1p36 deletion syndrome;607872 17918734;22766398;18245432 False 3 0;0;0 30.556 False 1 898703 6229913 3 60 cnv_loss 1p36 terminal region (includes GABRD) Loss ISCA-37439-Gain region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) 28300815;Chromosome Xq duplication syndrome 17546640;20004760;18047645 False 3 0;0;0 30.556 False X 154396223 154555683 3 60 cnv_gain Xq28 recurrent region (includes GDI1) Gain ISCA-37440-Loss region Expert Review Green Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal hyperphagia;lactic acidemia;mild/moderate mental retardation;Hypotonia-cystinuria syndrome (HCS);606407;failure to thrive;nephrolithiasis;rapid weight gain in late childhood;minor facial dysmorphism;growth hormone deficiency;facial dysmorphism;respiratory chain complex IV deficiency;cystinuria;neonatal seizures;2p21 deletion syndrome;hypotonia;severe somatic and developmental delay 18234729;11524703;16385448 False 3 0;0;0 30.556 False 2 44183133 44362502 30 60 cnv_loss 2p21 region (includes PREPL and SLC3A1) Loss ISCA-37440-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal mild/moderate mental retardation;facial dysmorphism;Hypotonia-cystinuria syndrome (HCS);2p21 deletion syndrome;rapid weight gain in late childhood;failure to thrive;growth hormone deficiency;606407;lactic acidemia;respiratory chain complex IV deficiency;hyperphagia;minor facial dysmorphism;severe somatic and developmental delay;nephrolithiasis;cystinuria;neonatal seizures;hypotonia 11524703;18234729;16385448 False 3 0;0;0 30.556 False 2 44183133 44362502 30 60 cnv_loss 2p21 region (includes PREPL and SLC3A1) Loss ISCA-37440-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology BIALLELIC, autosomal or pseudoautosomal mild/moderate mental retardation;facial dysmorphism;Hypotonia-cystinuria syndrome (HCS);2p21 deletion syndrome;rapid weight gain in late childhood;failure to thrive;growth hormone deficiency;606407;lactic acidemia;respiratory chain complex IV deficiency;hyperphagia;minor facial dysmorphism;severe somatic and developmental delay;nephrolithiasis;cystinuria;neonatal seizures;hypotonia 11524703;18234729;16385448 False 3 0;0;0 30.556 False 2 44183133 44362502 30 60 cnv_loss 2p21 region (includes PREPL and SLC3A1) Loss ISCA-37441-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Potocki-Shaffer syndrome;multiple exostoses;biparietal foramina;intellectual disability;strabismus;minor craniofacial anomalies;myopia;ophthalmologic anomalies;601224;mental retardation;enlarged anterior fontanel;genital abnormalities in males;parietal foramina;developmental delay 15852040;16319823;20140962 False 3 0;0;0 30.556 False 11 43873250 46130899 3 60 cnv_loss 11p11.2 (Potocki-Shaffer syndrome) region (includes ALX4, EXT2) Loss ISCA-37443-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown . mild to moderate mental retardation, with only slightly dysmorphic facial features that were similar in most patients: long and narrow face, short philtrum, and high nasal bridge. Autism, gait ataxia, chest wall deformity, and long and tapering fingers were noted in at least 2 of the 6 patients. delayed psychomotor development with mild to moderate mental retardation and/or learning disabilities with speech delay. All had low birth weight, microcephaly, high nasal bridge, and short philtrum, and 3 had clinodactyly of the toes. primary pulmonary hypertension, patent ductus arteriosus (PDA), subvalvular aortic stenosis, and gastroesophageal reflux, and required neonatal intensive care for 57 days after birth due to complications of meconium aspiration. He had mild dysmorphic features, including posteriorly rotated ears, shallow orbits, frontal bossing, prominent nose, long thin lip, and broad face. He also had bilateral sandal gap toes, single palmar creases, and bilateral inguinal hernia. However, he was developmentally normal at age 6 months. delayed psychomotor development with delayed waking and poor motor skills, autism with speech delay, mental retardation, and psychiatric disturbances, including aggression, anxiety, hyperactivity, and bipolar disorder with psychosis in 1. Both had dysmorphic features, including high nasal bridge, asymmetric face, and crowded/dysplastic teeth;1 had micrognathia and epicanthal folds. Both had tapered fingers. 609425;Chromosome 3q29 microdeletion syndrome False 3 0;0;0 30.556 False 3 196029183 197617791 3 60 cnv_loss 3q29 recurrent region (includes DLG1) Loss ISCA-37446-Gain region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown 608363;intellectual disability and congenital abnormalities,Autism;chromosome 22q11.2 microduplication;heart defects, urogenital abnormalities, velopharyngeal insufficiency with or without cleft palate, and ranging from multiple defects to mild learning difficulties with some individuals being essentially normal 23044707;22970919 False 3 0;0;0 30.556 False 22 18924718 21111383 3 60 cnv_gain 22q11.2 recurrent (DGS/VCFS) region (proximal, A-D) (includes TBX1) Gain ISCA-37446-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown neonatal hypocalcemia, which may present as tetany or seizures, due to hypoplasia of the parathyroid glands, and susceptibility to infection due to a deficit of T cells;micrognathia;clefting;Hearing deficits;Velocardiofacial syndrome;cardiac malformations;DiGeorge syndrome False 3 0;0;0 30.556 False 22 18924718 21111383 3 60 cnv_loss 22q11.2 recurrent (DGS/VCFS) region (proximal, A-D) (includes TBX1) Loss ISCA-37447-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Kagami-Ogata syndrome, OMIM:608149;Temple syndrome, OMIM:616222 20585555;24801763;27406249;33579810;18176563;28640239 False 3 100;0;0 30.556 False 14 100724515 100833215 3 60 cnv_loss DLK1-MEG3 Intergenic Region Loss ISCA-37448-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Developmental delay/intellectual disability, epilepsy, autism spectrum disorder, schizophrenia, congenital heart disease, and variable dysmorphic features 31451536;24352232;30767844;31665216 False 3 100;0;0 30.556 False 15 22782170 23040134 3 60 cnv_loss 15q11.2 recurrent region (BP1-BP2) (includes NIPA1) Loss ISCA-37468-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) episodes of sudden loss of muscle tone;severe intellectual disability;exiting behavior;short stature;eleveated serotonin levels;autistic features;lip-smacking;hypotonia;stereotypical hand movements 20485326;22365943;23414621 False 3 0;0;0 30.556 False X 43654906 43882474 3 60 cnv_loss Xp11.23 region (includes MAOA and MAOB) Loss ISCA-37478-Gain region ClinGen;Other;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown hypotonia and motor delays, intellectual disability, autism spectrum disorder (ASD), and epilepsy including infantile spasms, 608636;chromosome 15q11-q13 duplication syndrome;autism, mental retardation, ataxia, seizures, developmental delays, and behavioral problems 18374305;16840569;9106540 False 3 0;0;0 30.556 False 15 23465365 28134728 3 60 cnv_gain 15q11q13 recurrent (PWS/AS) region (BP2-BP3, Class 2) Gain ISCA-37478-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown microcephaly;Developmental delay, muscle weakness;Mental retardation;Angelman syndrome;176270;Prader-Willi syndrome;105830 22045295;7611294 False 3 0;0;0 30.556 False 15 23465365 28134728 3 60 cnv_loss 15q11q13 recurrent (PWS/AS) region (BP2-BP3, Class 2) Loss ISCA-37486-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown developmental delay;613444;obesity 23258348;19966786;20808231 False 3 0;0;0 30.556 False 16 28811314 29035178 3 60 cnv_loss 16p11.2 recurrent region (includes SH2B1) (distal region) (BP2-BP3) Loss ISCA-37493-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown microcephaly;seizures;agenesis of the corpus callosum;intellectual disability;hand and foot anomalies;612337;non-specific craniofacial anomalies;hypoplasia;psychomotor retardation;hypogenesis of the corpus callosum 21800092;17603806;22678713 False 3 0;0;0 30.556 False 1 243124428 245154985 3 60 cnv_loss 1q43q44 terminal region (includes AKT3) Loss ISCA-37494-Gain region Expert Review Green;Expert list Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Chromosome Xq28 duplication syndrome, 300815;X linked intellectual disability (XLID);PMID: 25927380 cognitive impairment, behavioral problems, distinctive facial features;duplication affects males with a recognizable syndrome, females exhibiting milder phenotypes;PMID:21984752 behavioural abnormalities (hyperactivity and aggressiveness), characteristic facial features (high forehead, upper eyelid fullness, broad nasal bridge and thick lower lip);PMID:24357492 Cognitive impairment in male patients 25927380;21984752;24357492 False 3 100;0;0 30.556 False X 154890328 155335092 3 60 cnv_gain Xq28 recurrent region (int22h1/int22h2-flanked) (includes RAB39B) Gain ISCA-37494-Loss region Expert Review Green;Expert list Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) PMID: 25927380 cognitive impairment, behavioral problems, distinctive facial features;deletion results in skewed chromosome X inactivation and no clinical phenotype in females;PMID: 21984752 in utero male lethality with deletions 25927380;21984752 False 3 100;0;0 30.556 False X 154890328 155335092 3 60 cnv_loss Xq28 recurrent region (int22h1/int22h2-flanked) (includes RAB39B) Loss ISCA-37495-Loss region ClinGen;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown 26227573 False 3 100;0;0 30.556 False 2 96073264 97005692 3 60 cnv_loss 2q11.2 recurrent region (includes ARID5A, TMEM127) Loss ISCA-37498-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Developmental delay/intellectual disability, dysmorphic features, dental anomalies, long slender fingers with 5th finger clinodactyly, and additional clinical features 28211979;21373257;37152320 False 3 100;0;0 30.556 False 11 67996175 71525885 3 60 cnv_loss 11q13.2q13.4 recurrent region (includes SHANK2, FGFs) Loss ISCA-37500-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown mild to moderate cognitive deficit;Diamond-Blackfan anemia;intellectual disability;614294;anemia;congenital diaphragmatic hernia;cryptorchidism in males;severe speech and psychomotor delay;mental retardation;postnatal short stature;behavioral problem;mild dysmorphic feature;developmental delay 23166063;17847001;24352913 False 3 0;0;0 30.556 False 15 82534140 84045981 3 60 cnv_loss 15q25.2 recurrent region (LCR B-C, proximal) Loss ISCA-37501-Loss region Expert Review Green;Expert list Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Chromosome 17q23.1-q23.2 deletion syndrome, 613355;PMID:20206336 mild to moderate developmental delay (particularly speech delay), microcephaly, postnatal growth retardation, heart defects, hand, foot and limb abnormalities;PMID: 22052739 Developmental delay, heart defects, microcephaly, postnatal growth retardation, hand, foot and limb abnormalities, sensorineural hearing loss 20206336;22052739 False 3 100;0;0 30.556 False 17 60035641 62198448 3 60 cnv_loss 17q23.1q23.2 recurrent region (includes TBX2, TBX4) Loss ISCA-46290-Gain region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, biallelic mutations in females Idiopathic mental retardation, speech delay, and a peculiar electroencephalographic (EEG) pattern in childhood. Autism and epilepsy, severe intellectual disability and dysmorphic facial features. Moderate to severe intellectual disability, early onset of puberty, language impairment, and age related epileptic syndromes such as West syndrome and focal epilepsy with activation during sleep evolving in some patients to continuous spikes-and-waves during slow sleep;300801 25425167;19716111;21418194 False 3 0;0;0 30.556 False X 48447780 52444264 3 60 cnv_gain Xp11.22p11.23 recurrent region (includes SHROOM4) Gain ISCA-46292-Loss region ClinGen;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown 21671380;21187175;17541642;19938088;21412926;21208904;15957176 False 3 100;0;0 30.556 False 22 21562828 24598466 3 60 cnv_loss 22q11.2 recurrent region (distal type III, D-G/H) (includes SMARCB1) Loss ISCA-46295-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown seizures;20236110;mental retardation;22775350;dysmorphic features;developmental delay;severe epileptic encephalopathy 19898479;20236110;22775350;29395075;29395074 False 3 0;0;0 30.556 False 15 31727418 32153204 3 60 cnv_loss 15q13.3 recurrent region (D-CHRNA7 to BP5) (includes CHRNA7 and OTUD7A) Loss ISCA-46296-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Developmental delays, intellectual disability, brain anomalies, non-specific craniofacial abnormalities, hypotonia, ocular abnormalities, hearing loss, and other variable clinical features 22180641;19921647 False 3 100;0;0 30.556 False 15 72671374 75215971 3 60 cnv_loss 15q24 recurrent region (LCR A-LCR C) Loss ISCA-46297-Loss region ClinGen;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown 31204719;19888295;20301607;25719193;30836598 False 3 100;0;0 30.556 False 16 21558792 21729102 30 60 cnv_loss 16p12.2 recurrent region (distal)(includes OTOA) Loss ISCA-46299-Gain region Expert Review Green;Expert list Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) X linked intellectual disability (XLID);PMID: 26692240 Mild profound intellectual disability, speech delay, failure to thrive, hand abnormalities, motor delay, abnormal palate;PMID:22840365 Mild intellectual disability;PMID:26692240 Region 2 (53,160,114 53,713,154 bp Within Chromosome Xp11.22) 22840365;20655035;26692240 False 3 100;0;0 30.556 False X 53334251 53766556 3 60 cnv_gain Xp11.22 region (includes HUWE1) Gain ISCA-46300-Loss region Expert Review Green;ClinGen Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Developmental delays/intellectual disability, brain anomalies, craniofacial abnormalities, hypermobile joints, digital findings, and other variable clinical features 27399968;22180641 False 3 100;0;0 30.556 False 15 75339446 75680568 3 60 cnv_loss 15q24 recurrent region (LCR C-LCR D) (includes SIN3A) Loss ISCA-46304-Gain region ClinGen;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) 22679399;29141583;29618507;32043567 False 3 100;0;0 30.556 False X 154008529 154110279 3 60 cnv_gain Xq28 region (includes MECP2) Gain ISCA-46553-Loss region ClinGen;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown 21204220;15338008;22067867;21471554;28503614 False 3 100;0;0 30.556 False 3 136684193 148623326 3 60 cnv_loss 3q24 Region (includes ZIC1) Loss ISCA-46742-Loss region ClinGen;Expert Review Green Childhood onset leukodystrophy Neurology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown 27633570;32562408;29274487;29220674 False 3 100;0;0 30.556 False 7 5497217 5760091 3 60 cnv_loss 7p22.1 region (includes ACTB) Loss ISCA-46743-Gain region ClinGen;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) 23637084;24733578;26443594;25677961;31609727 False 3 100;0;0 30.556 False X 123900469 124102669 3 60 cnv_gain Xq25 region (includes STAG2) Gain ISCA-46743-Loss region ClinGen;Expert Review Green Childhood onset leukodystrophy Neurology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) 30158690;33758131 False 3 100;0;0 30.556 False X 123900469 124102669 3 60 cnv_loss Xq25 region (includes STAG2) Loss