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White matter disorders and cerebral calcification - narrow panel v4.3 PPFIBP1 Arina Puzriakova reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v4.3 ESAM Arina Puzriakova reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v3.35 NAA60 Sarah Leigh changed review comment from: To date, NAA60 variants are not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38480682 reports six NAA60 variants in six unrelated cases with an autosomal recessive primary familial brain calcification (PFBC). Table 2 in PMID: 38480682 outlines the extent of the calcification seen in the patient's CT scans. Functional studies show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro, and loss of function by the NAA60 variants results in a reduced level of surface SLC20A2, thereby, reducing the extracellular phosphate uptake. The authors conclude, that this study provides a possible biochemical explanation of the involvement of NAA60 variants in PFBC development (PMID: 38480682).
Sources: Literature; to: To date, NAA60 variants are not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38480682 reports six NAA60 variants in six unrelated cases with an autosomal recessive primary familial brain calcification (PFBC). Table 2 in PMID: 38480682 outlines the extent of the calcification seen in the patient's CT scans. Functional studies show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro, and loss of function by the NAA60 variants results in a reduced level of surface SLC20A2, thereby, reducing the extracellular phosphate uptake. The authors conclude, that this study provides a possible biochemical explanation of the involvement of NAA60 variants in PFBC development (PMID: 38480682).
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v3.35 NAA60 Sarah Leigh Mode of inheritance for gene: NAA60 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v3.33 NAA60 Sarah Leigh gene: NAA60 was added
gene: NAA60 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Q2_24_promote_green, Q2_24_NHS_review tags were added to gene: NAA60.
Mode of inheritance for gene: NAA60 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NAA60 were set to 38480682
Phenotypes for gene: NAA60 were set to NAA60 associated autosomal recessive primary familial brain calcifications
Review for gene: NAA60 was set to GREEN
Added comment: To date, NAA60 variants are not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38480682 reports six NAA60 variants in six unrelated cases with an autosomal recessive primary familial brain calcification (PFBC). Table 2 in PMID: 38480682 outlines the extent of the calcification seen in the patient's CT scans. Functional studies show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro, and loss of function by the NAA60 variants results in a reduced level of surface SLC20A2, thereby, reducing the extracellular phosphate uptake. The authors conclude, that this study provides a possible biochemical explanation of the involvement of NAA60 variants in PFBC development (PMID: 38480682).
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v3.29 HMBS Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated families reported with white matter abnormalities. Hence, this gene can be promoted to green rating in the next GMS review.
White matter disorders and cerebral calcification - narrow panel v3.26 HMBS Achchuthan Shanmugasundram changed review comment from: PMID:27558376 reported three siblings with compound heterozygous missense HMBS variants (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln) and a disease characterised by childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. They had a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons, and cerebellar atrophy was present in advanced disease stages.

PMID:34089223 reported two patients from a family with homozygous variant (c.251C>A/ p.Ala84Asp) and another patient from a different family with the same compound heterozygous variants as the siblings reported in PMID:27558376 (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln). All patients presented with slowly progressive spasticity, ataxia, peripheral neuropathy, with or without mild cognitive impairment, and/or ocular disease with onset in childhood or adolescence. Their brain MRIs show mainly confluent signal abnormalities in the periventricular and deep white matter and bilateral thalami. However, the onset of the disease was during childhood in individuals with the homozygous variant (7 years and late childhood), while the onset was at 22 years of age in the third individual with compound heterozygous variants.

Monoallelic variants in HMBS gene has been associated with acute intermittent porphyria (MIM #176000) in OMIM, but biallelic variants have not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.; to: PMID:27558376 reported three siblings with compound heterozygous missense HMBS variants (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln) and a disease characterised by childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. They had a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons, and cerebellar atrophy was present in advanced disease stages.

PMID:34089223 reported two patients from a family with homozygous variant (c.251C>A/ p.Ala84Asp) and another patient from a different family with the same compound heterozygous variants as the siblings reported in PMID:27558376 (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln). All patients presented with slowly progressive spasticity, ataxia, peripheral neuropathy, with or without mild cognitive impairment, and/or ocular disease with onset in childhood or adolescence. Their brain MRIs show mainly confluent signal abnormalities in the periventricular and deep white matter and bilateral thalami. However, the onset of the disease was during childhood in individuals with the homozygous variant (7 years and late childhood), while the onset was at 22 years of age in the third individual with compound heterozygous variants.

Monoallelic variants in HMBS gene have been associated with acute intermittent porphyria (MIM #176000) in OMIM, but biallelic variants have not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
White matter disorders and cerebral calcification - narrow panel v3.26 HMBS Achchuthan Shanmugasundram changed review comment from: PMID:27558376 reported three siblings with compound heterozygous missense HMBS variants (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln) and a disease characterised by childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. They had a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons, and cerebellar atrophy was present in advanced disease stages.

PMID:34089223 reported two patients from a family with homozygous variant (c.251C>A/ p.Ala84Asp) and another patient from a different family with the same compound heterozygous variants as the siblings reported in PMID:27558376 (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln). All patients presented with slowly progressive spasticity, ataxia, peripheral neuropathy, with or without mild cognitive impairment, and/or ocular disease with onset in childhood or adolescence. Their brain MRIs show mainly confluent signal abnormalities in the periventricular and deep white matter and bilateral thalami. However, the onset of the disease was during childhood in individuals with the homozygous variant (7 years and late childhood), while the onset was at 22 years of age in the third individual with compound heterozygous variants.

; to: PMID:27558376 reported three siblings with compound heterozygous missense HMBS variants (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln) and a disease characterised by childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. They had a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons, and cerebellar atrophy was present in advanced disease stages.

PMID:34089223 reported two patients from a family with homozygous variant (c.251C>A/ p.Ala84Asp) and another patient from a different family with the same compound heterozygous variants as the siblings reported in PMID:27558376 (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln). All patients presented with slowly progressive spasticity, ataxia, peripheral neuropathy, with or without mild cognitive impairment, and/or ocular disease with onset in childhood or adolescence. Their brain MRIs show mainly confluent signal abnormalities in the periventricular and deep white matter and bilateral thalami. However, the onset of the disease was during childhood in individuals with the homozygous variant (7 years and late childhood), while the onset was at 22 years of age in the third individual with compound heterozygous variants.

Monoallelic variants in HMBS gene has been associated with acute intermittent porphyria (MIM #176000) in OMIM, but biallelic variants have not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
White matter disorders and cerebral calcification - narrow panel v3.26 HMBS Achchuthan Shanmugasundram changed review comment from: PMID:27558376 reported three siblings with compound heterozygous missense HMBS variants and a disease characterised by childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. They had a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons, and cerebellar atrophy was present in advanced disease stages.

PMID:34089223 reported three patients from two unrelated families with; to: PMID:27558376 reported three siblings with compound heterozygous missense HMBS variants (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln) and a disease characterised by childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. They had a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons, and cerebellar atrophy was present in advanced disease stages.

PMID:34089223 reported two patients from a family with homozygous variant (c.251C>A/ p.Ala84Asp) and another patient from a different family with the same compound heterozygous variants as the siblings reported in PMID:27558376 (c.500G>A/ p.Arg167Gln & c.674G>A/ p.Arg225Gln). All patients presented with slowly progressive spasticity, ataxia, peripheral neuropathy, with or without mild cognitive impairment, and/or ocular disease with onset in childhood or adolescence. Their brain MRIs show mainly confluent signal abnormalities in the periventricular and deep white matter and bilateral thalami. However, the onset of the disease was during childhood in individuals with the homozygous variant (7 years and late childhood), while the onset was at 22 years of age in the third individual with compound heterozygous variants.
White matter disorders and cerebral calcification - narrow panel v3.26 HMBS Achchuthan Shanmugasundram reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: None; Publications: 27558376, 34089223; Phenotypes: Leukoencephalopathy, HP:0002352; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v3.25 NOTCH3 Arina Puzriakova Mode of inheritance for gene: NOTCH3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
White matter disorders and cerebral calcification - narrow panel v3.24 NOTCH3 Arina Puzriakova Phenotypes for gene: NOTCH3 were changed from CEREBRAL ARTERIOPATHY, AUTOSOMAL DOMINANT, WITH SUBCORTICAL INFARCTS AND LEUKOENCEPHALOPATHY to Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, OMIM:125310
White matter disorders and cerebral calcification - narrow panel v3.21 SCAF4 Arina Puzriakova Phenotypes for gene: SCAF4 were changed from SCAF4-related Neurodevelopmental Disorder; Intellectual disability; Seizures; Behavioural abnormalities to Fliedner-Zweier syndrome, OMIM:620511
White matter disorders and cerebral calcification - narrow panel v3.20 PPFIBP1 Arina Puzriakova gene: PPFIBP1 was added
gene: PPFIBP1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature,Expert Review Amber
Q2_23_promote_green tags were added to gene: PPFIBP1.
Mode of inheritance for gene: PPFIBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPFIBP1 were set to 35830857; 30214071
Phenotypes for gene: PPFIBP1 were set to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Penetrance for gene: PPFIBP1 were set to Complete
White matter disorders and cerebral calcification - narrow panel v3.19 ENTPD1 Eleanor Williams reviewed gene: ENTPD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v3.19 CLDN5 Eleanor Williams reviewed gene: CLDN5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
White matter disorders and cerebral calcification - narrow panel v3.19 C2orf69 Eleanor Williams reviewed gene: C2orf69: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v3.17 ESAM Achchuthan Shanmugasundram gene: ESAM was added
gene: ESAM was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Amber,Literature,Expert Review
Q3_23_promote_green, Q3_23_NHS_review tags were added to gene: ESAM.
Mode of inheritance for gene: ESAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESAM were set to 36996813
Phenotypes for gene: ESAM were set to Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity, OMIM:620371
White matter disorders and cerebral calcification - narrow panel v3.16 HPDL Sarah Leigh edited their review of gene: HPDL: Added comment: Biallelic HPDL variants have been associated with Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (OMIM:619026) and Spastic paraplegia 83, autosomal recessive (OMIM:619027) in OMIM and as a Strong gene for HPDL Neurodegenerative Disease in Gen2Phen.
PMIDs 32707086 and 33188300 report white matter changes in 16/28 individuals from 9/18 families where MRI assessments were available.; Changed rating: GREEN
White matter disorders and cerebral calcification - narrow panel v3.15 HPDL Sarah Leigh gene: HPDL was added
gene: HPDL was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature,Expert Review Green
gene-checked tags were added to gene: HPDL.
Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPDL were set to 32707086; 33188300
Phenotypes for gene: HPDL were set to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026; Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613
White matter disorders and cerebral calcification - narrow panel v3.11 CLDN5 Achchuthan Shanmugasundram gene: CLDN5 was added
gene: CLDN5 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN5 were set to 36477332
Phenotypes for gene: CLDN5 were set to epilepsy, MONDO:0005027
Review for gene: CLDN5 was set to GREEN
Added comment: PMID: 36477332 identified de novo heterozygous missense variants in CLDN5 in fifteen unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v3.9 ENTPD1 Achchuthan Shanmugasundram changed review comment from: PMID:35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.
Sources: Literature; to: PMID:35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals (from 9 families) and epilepsy in 7 individuals.

In addition, it was also reviewed here that two unrelated families were previously reported with white matter abnormalities.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v3.9 ENTPD1 Achchuthan Shanmugasundram gene: ENTPD1 was added
gene: ENTPD1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Mode of inheritance for gene: ENTPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ENTPD1 were set to 35471564
Phenotypes for gene: ENTPD1 were set to Spastic paraplegia 64, autosomal recessive, OMIM:615683
Review for gene: ENTPD1 was set to GREEN
Added comment: PMID:35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v3.8 C2orf69 Arina Puzriakova gene: C2orf69 was added
gene: C2orf69 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Amber,Literature
Q2_23_promote_green tags were added to gene: C2orf69.
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2orf69 were set to 34038740; 33945503
Phenotypes for gene: C2orf69 were set to Combined oxidative phosphorylation deficiency 53, OMIM:619423
White matter disorders and cerebral calcification - narrow panel v3.5 SUCLA2 Arina Puzriakova Phenotypes for gene: SUCLA2 were changed from Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria); Mitochondrial Leukoencephalopathy; Mitochondrial DNA depletion syndrome 5 to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073
White matter disorders and cerebral calcification - narrow panel v3.2 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, MIM#607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
White matter disorders and cerebral calcification - narrow panel v2.9 PEX6 Sarah Leigh commented on gene: PEX6: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
White matter disorders and cerebral calcification - narrow panel v2.8 PEX6 Sarah Leigh Source NHS GMS was added to PEX6.
Mode of inheritance for gene PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v2.8 CSF1R Sarah Leigh Source NHS GMS was added to CSF1R.
Mode of inheritance for gene CSF1R was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v2.8 ACOX1 Sarah Leigh Source NHS GMS was added to ACOX1.
Mode of inheritance for gene ACOX1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v2.7 PAFAH1B1 Arina Puzriakova Phenotypes for gene: PAFAH1B1 were changed from Lissencephaly 1; Cerebral Malformation Disorders; Lissencephaly/Subcortical Band Heterotopia to Lissencephaly 1, OMIM:607432; Subcortical laminar heterotopia, OMIM:607432
White matter disorders and cerebral calcification - narrow panel v2.6 DCX Arina Puzriakova Phenotypes for gene: DCX were changed from Lissencephaly, X-Linked, 1; Subcortical laminal heteropia, X-linked, 300067; Cerebral Malformation Disorders; Lissencephaly, X-linked, 300067; Classic Lissencephaly/Subcortical Band Heterotopia to Lissencephaly, X-linked, OMIM:300067; Subcortical laminal heterotopia, X-linked, OMIM:300067
White matter disorders and cerebral calcification - narrow panel v2.3 PDGFRB Achchuthan Shanmugasundram edited their review of gene: PDGFRB: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
White matter disorders and cerebral calcification - narrow panel v2.2 PDGFRB Achchuthan Shanmugasundram reviewed gene: PDGFRB: Rating: GREEN; Mode of pathogenicity: None; Publications: 34494111; Phenotypes: Basal ganglia calcification, idiopathic, 4, MIM# 615007, MONDO:0014004; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
White matter disorders and cerebral calcification - narrow panel v1.245 ACOX1 Arina Puzriakova Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency 264470; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Mitchell syndrome, OMIM:618960 to Peroxisomal acyl-CoA oxidase deficiency, OMIM:264470; Mitchell syndrome, OMIM:618960; General Leukodystrophy & Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v1.244 PEX6 Sarah Leigh changed review comment from: Comment on mode of inheritance: The mode of inheritance for PEX6 has been set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted for this gene, in order to highlight that unaffected parents may also carry rs61753230.; to: Comment on mode of inheritance: The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted for this gene, in order to highlight that unaffected parents may also carry rs61753230.
White matter disorders and cerebral calcification - narrow panel v1.243 BLOC1S1 Arina Puzriakova gene: BLOC1S1 was added
gene: BLOC1S1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
watchlist tags were added to gene: BLOC1S1.
Mode of inheritance for gene: BLOC1S1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BLOC1S1 were set to 33875846
Phenotypes for gene: BLOC1S1 were set to severe intellectual disability; severe global developmental delay; epilepsy
Penetrance for gene: BLOC1S1 were set to unknown
White matter disorders and cerebral calcification - narrow panel v1.241 SLC35B2 Sarah Leigh gene: SLC35B2 was added
gene: SLC35B2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature,Expert Review Amber
Mode of inheritance for gene: SLC35B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC35B2 were set to 35325049
Phenotypes for gene: SLC35B2 were set to Abnormality of the skeletal system; Short long bone; Short stature; Abnormality of epiphysis morphology; Scoliosis; Multiple joint dislocation; Global develpmental delay; Intellectual disability; CNS hypomyelination; Abnormality of the corpus callosum; Cerebral atrophy; Abnormality of the amniotic fluid
Penetrance for gene: SLC35B2 were set to Complete
White matter disorders and cerebral calcification - narrow panel v1.239 MAL Sarah Leigh Entity copied from Inherited white matter disorders v1.159
White matter disorders and cerebral calcification - narrow panel v1.239 MAL Sarah Leigh gene: MAL was added
gene: MAL was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: MAL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAL were set to 35217805
Phenotypes for gene: MAL were set to developmental delay; nystagmus; progressive motor deterioration; dysmyelination
White matter disorders and cerebral calcification - narrow panel v1.238 PEX6 Sarah Leigh changed review comment from: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted for this gene, in order to highlight that unaffected parents may also carry rs61753230.; to: Comment on mode of inheritance: The mode of inheritance for PEX6 has been set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted for this gene, in order to highlight that unaffected parents may also carry rs61753230.
White matter disorders and cerebral calcification - narrow panel v1.238 PEX6 Sarah Leigh changed review comment from: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.; to: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted for this gene, in order to highlight that unaffected parents may also carry rs61753230.
White matter disorders and cerebral calcification - narrow panel v1.237 SNORD118 Sarah Leigh Tag locus-type-small-nucleolar tag was added to gene: SNORD118.
White matter disorders and cerebral calcification - narrow panel v1.234 NDUFV2 Arina Puzriakova gene: NDUFV2 was added
gene: NDUFV2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
watchlist tags were added to gene: NDUFV2.
Mode of inheritance for gene: NDUFV2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFV2 were set to 33811136
Phenotypes for gene: NDUFV2 were set to Mitochondrial complex I deficiency, nuclear type 7, OMIM:618229; Progressive cavitating leukoencephalopathy, MONDO:0015349
Review for gene: NDUFV2 was set to AMBER
Added comment: Liu et al., 2022 (PMID: 33811136) report on two sibling pairs of two unrelated Chinese families presenting with progressive cavitating leukoencephalopathy associated with distinct biallelic variants in this gene. Functional analyses demonstrated impaired structural stability and function of the NDUFV2 protein and complex I deficiency was confirmed in affected individuals' fibroblasts and a muscle biopsy.

This is the first report linking NDUFV2 with a leukoencephalopathy phenotype and therefore rating as Amber for now until further cases emerge.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v1.230 PEX6 Sarah Leigh Added comment: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
White matter disorders and cerebral calcification - narrow panel v1.230 PEX6 Sarah Leigh Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.229 PEX6 Sarah Leigh reviewed gene: PEX6: Rating: ; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.228 PNPT1 Arina Puzriakova gene: PNPT1 was added
gene: PNPT1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Q1_22_rating tags were added to gene: PNPT1.
Mode of inheritance for gene: PNPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPT1 were set to 28594066; 30046113; 33199448
Phenotypes for gene: PNPT1 were set to Combined oxidative phosphorylation deficiency 13, OMIM:614932
Review for gene: PNPT1 was set to GREEN
Added comment: White matter abnormalities can be observed in some patients with PNPT1-related mitochondrial disease caused by biallelic variants. Overall at 6 least unrelated cases reported in literature with diminished white matter and/or delayed myelination which is sufficient to justify a Green rating on this panel.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v1.225 ACER3 Arina Puzriakova reviewed gene: ACER3: Rating: GREEN; Mode of pathogenicity: None; Publications: 34281620; Phenotypes: Leukodystrophy, progressive, early childhood-onset, OMIM:617762; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.221 TWNK Arina Puzriakova Mode of inheritance for gene TWNK was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.221 SLC25A4 Arina Puzriakova Mode of inheritance for gene SLC25A4 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.220 SNORD118 Jenny Simmonds reviewed gene: SNORD118: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33029936, 27571260; Phenotypes: Leukoencephalopathy, brain calcifications, and cysts; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.217 ELOVL1 Arina Puzriakova gene: ELOVL1 was added
gene: ELOVL1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list,Expert Review Amber
missense, Q4_21_rating tags were added to gene: ELOVL1.
Mode of inheritance for gene: ELOVL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELOVL1 were set to 23689133; 29496980; 30487246; 32123819
Phenotypes for gene: ELOVL1 were set to Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, OMIM:618527
White matter disorders and cerebral calcification - narrow panel v1.216 COLGALT1 Ivone Leong Phenotypes for gene: COLGALT1 were changed from Brain small vessel disease 3 MIM#618360 to Brain small vessel disease 3, OMIM:618360
White matter disorders and cerebral calcification - narrow panel v1.212 LMNB1 Arina Puzriakova Phenotypes for gene: LMNB1 were changed from Leukodystrophy,adult-onset, autosomal dominant,169500; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Adult onset autosomal dominant leukodystrophy (ADLD) to Leukodystrophy, adult-onset, autosomal dominant, OMIM:169500
White matter disorders and cerebral calcification - narrow panel v1.210 CSF1R Arina Puzriakova Added comment: Comment on mode of inheritance: CSF1R is associated with two relevant disorders both including white matter abnormalities and calcifications. One is an adult-onset rapidly progressive neurodegenerative disorder, associated with monoallelic inheritance (Leukoencephalopathy, diffuse hereditary, with spheroids, OMIM:221820). Conversely, biallelic variants cause a condition with a variable onset but mostly childhood (Brain abnormalities, neurodegeneration, and dysosteosclerosis, OMIM:618476).

Both phenotypes are relevant to this panel and therefore the MOI may be updated from 'Monoallelic' to 'Both mono- and biallelic' at the next GMS review.
White matter disorders and cerebral calcification - narrow panel v1.210 CSF1R Arina Puzriakova Mode of inheritance for gene: CSF1R was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
White matter disorders and cerebral calcification - narrow panel v1.209 CSF1R Arina Puzriakova Phenotypes for gene: CSF1R were changed from General Leukodystrophy & Mitochondrial Leukoencephalopathy to Leukoencephalopathy, diffuse hereditary, with spheroids, OMIM:221820; Brain abnormalities, neurodegeneration, and dysosteosclerosis, OMIM:618476
White matter disorders and cerebral calcification - narrow panel v1.205 ABHD16A Ivone Leong gene: ABHD16A was added
gene: ABHD16A was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature,Expert Review Amber
Q4_21_rating tags were added to gene: ABHD16A.
Mode of inheritance for gene: ABHD16A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD16A were set to 34587489
Phenotypes for gene: ABHD16A were set to Spastic paraplegia; Intellectual disability
White matter disorders and cerebral calcification - narrow panel v1.204 ATP11A Ivone Leong gene: ATP11A was added
gene: ATP11A was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature,Expert Review Amber
watchlist tags were added to gene: ATP11A.
Mode of inheritance for gene: ATP11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP11A were set to 34403372
Phenotypes for gene: ATP11A were set to Neurodevelopmental disorder
White matter disorders and cerebral calcification - narrow panel v1.203 RNF220 Ivone Leong Phenotypes for gene: RNF220 were changed from Leukodystrophy; CNS hypomyelination; Ataxia; Intellectual disability; Sensorineural hearing impairment; Elevated hepatic transaminases; Hepatic fibrosis; Dilated cardiomyopathy; Spastic paraplegia; Dysarthria; Abnormality of the corpus callosum to Leukodystrophy, MONDO:0019046; Abnormal corpus callosum morphology, HP:0001273
White matter disorders and cerebral calcification - narrow panel v1.202 RNF220 Ivone Leong gene: RNF220 was added
gene: RNF220 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Other,Expert Review Amber,Literature
Mode of inheritance for gene: RNF220 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNF220 were set to 33964137; 10881263
Phenotypes for gene: RNF220 were set to Leukodystrophy; CNS hypomyelination; Ataxia; Intellectual disability; Sensorineural hearing impairment; Elevated hepatic transaminases; Hepatic fibrosis; Dilated cardiomyopathy; Spastic paraplegia; Dysarthria; Abnormality of the corpus callosum
Penetrance for gene: RNF220 were set to Complete
White matter disorders and cerebral calcification - narrow panel v1.198 COLGALT1 Zornitza Stark gene: COLGALT1 was added
gene: COLGALT1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Mode of inheritance for gene: COLGALT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COLGALT1 were set to 30412317; 33709034; 31759980
Phenotypes for gene: COLGALT1 were set to Brain small vessel disease 3 MIM#618360
Review for gene: COLGALT1 was set to GREEN
Added comment: 3 unrelated cases with biallelic variants, and supporting functional assays. The main features of the cases were porencephalic cysts, leukoencephalopathy, lacunar infarcts, cerebral microbleeds/haemorrhages and calcifications. A null mouse model was embryonic lethal, but had defects in the vascular networks of the embryos.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v1.198 PI4KA Ivone Leong Entity copied from Ataxia and cerebellar anomalies - narrow panel v2.233
White matter disorders and cerebral calcification - narrow panel v1.198 PI4KA Ivone Leong gene: PI4KA was added
gene: PI4KA was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Amber
Q3_21_rating tags were added to gene: PI4KA.
Mode of inheritance for gene: PI4KA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PI4KA were set to 25855803; 34415322; 34415310
Phenotypes for gene: PI4KA were set to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, OMIM:616531
White matter disorders and cerebral calcification - narrow panel v1.197 GJA1 Arina Puzriakova Phenotypes for gene: GJA1 were changed from Oculodentodigital dysplasia, autosomal recessive 257850; Oculodentodigital dysplasia (AD) 164200 to Oculodentodigital dysplasia, OMIM:164200; Oculodentodigital dysplasia, autosomal recessive, OMIM:257850
White matter disorders and cerebral calcification - narrow panel v1.192 NKX6-2 Arina Puzriakova Phenotypes for gene: NKX6-2 were changed from Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy to Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy, OMIM:617560
White matter disorders and cerebral calcification - narrow panel v1.188 FARSA Zornitza Stark edited their review of gene: FARSA: Added comment: PMID 33598926: three additional families reported. Functional evidence was obtained with reduced FARS1 enzyme activity levels in fibroblasts or EBV-transformed lymphoblastoid cell lines (EBV-LCLs) of patients. Common to all was a chronic interstitial lung disease starting early in life and characterized by bilateral ground-glass opacification on HR-CT, and cholesterol pneumonitis in lung histology. Additional abnormalities in other organ systems include liver disease, neurological manifestations, and growth restriction.; Changed rating: GREEN; Changed publications to: 31355908, 33598926; Changed phenotypes to: Rajab interstitial lung disease with brain calcifications 2, MIM# 619013
White matter disorders and cerebral calcification - narrow panel v1.188 ACOX1 Ivone Leong changed review comment from: PMID: 32169171. 3 unrelated patients with the same de novo variant (N237S) with a progressive disease. Age of onset is between 3-12 years old (cf to AR patients 0-3 years old), disease course is progressive (AR patients, early onset and severe) white matter demyelination is progressive, sensorineural hearing loss and ataxia. Authors found that the variant increased levels of ACOX1 protein and function which increased levels of ROS in glia of Drosphila and mouse Schwann cells leading to glial degeneration. The authors suggested that the variant caused a GOF effect.

Therefore, MOI should be changed from Biallelic to Both monoallelic and biallelic (but biallelic mutations cuase a more severe disease form).; to: Comment on mode of inheritance: PMID: 32169171. 3 unrelated patients with the same de novo variant (N237S) with a progressive disease. Age of onset is between 3-12 years old (cf to AR patients 0-3 years old), disease course is progressive (AR patients, early onset and severe) white matter demyelination is progressive, sensorineural hearing loss and ataxia. Authors found that the variant increased levels of ACOX1 protein and function which increased levels of ROS in glia of Drosphila and mouse Schwann cells leading to glial degeneration. The authors suggested that the variant caused a GOF effect. AD causes Mitchell syndrome (OMIM:618960) and AR causes Peroxisomal acyl-CoA oxidase deficiency (OMIM:264470).

Therefore, MOI should be changed from Biallelic to Both monoallelic and biallelic (but biallelic mutations cuase a more severe disease form).
White matter disorders and cerebral calcification - narrow panel v1.188 ACOX1 Ivone Leong Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency 264470; General Leukodystrophy & Mitochondrial Leukoencephalopathy to Peroxisomal acyl-CoA oxidase deficiency 264470; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Mitchell syndrome, OMIM:618960
White matter disorders and cerebral calcification - narrow panel v1.187 ACOX1 Ivone Leong reviewed gene: ACOX1: Rating: ; Mode of pathogenicity: None; Publications: 32169171; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.185 KIAA1161 Ivone Leong Added comment: Comment on mode of inheritance: MOI has been changed from "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" to "Biallelic, autosomal or pseudoautosomal" after consulting the Genomics England Clinical Team. As not all carriers exhibit the phenotype and the age of for the carriers that do exhibit the phenotype is not appropriate for this panel. Therefore the Biallelic MOI was assigned.
White matter disorders and cerebral calcification - narrow panel v1.185 KIAA1161 Ivone Leong Mode of inheritance for gene: KIAA1161 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.182 AUH Ivone Leong gene: AUH was added
gene: AUH was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list,Expert Review Amber
Q2_21_rating tags were added to gene: AUH.
Mode of inheritance for gene: AUH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AUH were set to 20855850; 17130438
Phenotypes for gene: AUH were set to 3-methylglutaconic aciduria, type I, OMIM:250950
White matter disorders and cerebral calcification - narrow panel v1.167 SPG11 Ivone Leong Phenotypes for gene: SPG11 were changed from Spastic paralplegia 11, autosomal recessive, MIM#604360 to Spastic paralplegia 11, autosomal recessive, OMIM:604360
White matter disorders and cerebral calcification - narrow panel v1.165 NAXD Ivone Leong commented on gene: NAXD: Affected individuals show normal early development followed by acute psychomotor regression with ataxia, hypotonia, and sometimes seizures triggered by acute fever. The affected infants usually die in the first few years of life. Brain imaging shows multiple abnormalities, including brain edema and white matter abnormalities. The infants also present with skin lesions/rash.
White matter disorders and cerebral calcification - narrow panel v1.157 CYP7B1 Arina Puzriakova reviewed gene: CYP7B1: Rating: AMBER; Mode of pathogenicity: None; Publications: 19187859, 19439420, 24117163; Phenotypes: Spastic paraplegia 5A, autosomal recessive , OMIM:270800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.156 CYP7B1 Arina Puzriakova Phenotypes for gene: CYP7B1 were changed from to Spastic paraplegia 5A, autosomal recessive , OMIM:270800
White matter disorders and cerebral calcification - narrow panel v1.150 CNTNAP1 Arina Puzriakova reviewed gene: CNTNAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28374019, 29511323, 29882456; Phenotypes: Hypomyelinating neuropathy, congenital, 3, OMIM:618186; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.149 CLPP Ivone Leong changed review comment from: Comment on publications: PMID: 23541340, describes 3 consanguineous Pakistani families (PDF1, PKDF291 and DEM4395), all affected individuals had sensorineural hearing loss. Family PDF1: 3 affected sisters, 1/3 had delayed puberty, streak ovaries and hormone levels consistant with hypogonadotropic hypogonadism, 2/3 had incipient POF and 1/3 had white matter phenotype. All three had epilepsy, short stature, microcephaly (< 3 percentile), moderate learning difficulties and ataxia.
Family PKDF291: 4 affected females with primary amenorrhea and hypogonadotropic hypogonadism. 3/4 had rudimentary uterus and small ovaries, 1/4 had small uterus and normal sized ovaries. No learning disabilities, microcephaly, short stature, epilepsy or neurological deficiet in all affected females.
Family DEM4395: 1 affected male and 2 affected females. All females had normal periods but their hormone profiles were not investigated. Aside from hearing loss there were no other self reported medical problems.

PMID: 25956234. Consanguineous Saudi family with 1 affected male and 1 affected female. Both patients have hearing loss, growth retardation and mental retardation, spastic diplegia and mild-severe white matter loss. No seizures were described in the patients. There is a third sibling (8 months) with the same variant; however, he did not show any of the phenotypes seen in his siblings but he is under regular checkups from a clinical team.

PMID:26970254. Consanguineous family of Arabic descent. Proband with 4 unaffected siblings and parents. Proband has hearing loss, azoospermia, no neurological symptoms other than the foot drop (neurophysiology revealed a sensory-motor demyelinative axonal peripheral neuropathy of the lower limbs). Father has cerebellar ataxia (cause unknown).

PMID: 27087618. Non-consanguineous Turkish family; however, parents are from the same village. 2 affected siblings (1 male, 1 female). Sister has secondary amenorrhea, hearing loss, no ovaries detected, hypogonadotropic hypogonadism, no neurological problems. Brother has hearing loss but no other problems.

PMID: 27650058. Consanguineous Algerian family with 2 affected females. Both have hearing loss and secondary amenorrhea, but no other neurological symptoms.

PMID: 27899912. 3 affected families (1 - 3), with 5 affected individuals (all males). All had congenital deafness, psychomotor retardation, white matter phenotype and short stature. Patients were not tested for infertility.; to: Comment on publications: PMID: 23541340, describes 3 consanguineous Pakistani families (PDF1, PKDF291 and DEM4395), all affected individuals had sensorineural hearing loss. Family PDF1: 3 affected sisters, 1/3 had delayed puberty, streak ovaries and hormone levels consistant with hypogonadotropic hypogonadism, 2/3 had incipient POF and 1/3 had white matter phenotype. All three had epilepsy, short stature, microcephaly (< 3 percentile), moderate learning difficulties and ataxia.
Family PKDF291: 4 affected females with primary amenorrhea and hypogonadotropic hypogonadism. 3/4 had rudimentary uterus and small ovaries, 1/4 had small uterus and normal sized ovaries. No learning disabilities, microcephaly, short stature, epilepsy or neurological deficiet in all affected females.
Family DEM4395: 1 affected male and 2 affected females. All females had normal periods but their hormone profiles were not investigated. Aside from hearing loss there were no other self reported medical problems.

PMID: 25956234. Consanguineous Saudi family with 1 affected male and 1 affected female. Both patients have hearing loss, growth retardation and mental retardation, spastic diplegia and mild-severe white matter loss. No seizures were described in the patients. There is a third sibling (8 months) with the same variant; however, he did not show any of the phenotypes seen in his siblings but he is under regular checkups from a clinical team.

PMID:26970254. Consanguineous family of Arabic descent. Proband with 4 unaffected siblings and parents. Proband has hearing loss, azoospermia, no neurological symptoms other than the foot drop (neurophysiology revealed a sensory-motor demyelinative axonal peripheral neuropathy of the lower limbs). Father has cerebellar ataxia (cause unknown).

PMID: 27087618. Non-consanguineous Turkish family; however, parents are from the same village. 2 affected siblings (1 male, 1 female). Sister has secondary amenorrhea, hearing loss, no ovaries detected, hypogonadotropic hypogonadism, no neurological problems. Brother has hearing loss but no other problems.

PMID: 27650058. Consanguineous Algerian family with 2 affected females. Both have hearing loss and secondary amenorrhea, but no other neurological symptoms.

PMID: 27899912. 3 affected families, with 5 affected individuals (all males). All had congenital deafness, psychomotor retardation, white matter phenotype and short stature. Patients were not tested for infertility.
White matter disorders and cerebral calcification - narrow panel v1.149 CLPP Ivone Leong Added comment: Comment on publications: PMID: 23541340, describes 3 consanguineous Pakistani families (PDF1, PKDF291 and DEM4395), all affected individuals had sensorineural hearing loss. Family PDF1: 3 affected sisters, 1/3 had delayed puberty, streak ovaries and hormone levels consistant with hypogonadotropic hypogonadism, 2/3 had incipient POF and 1/3 had white matter phenotype. All three had epilepsy, short stature, microcephaly (< 3 percentile), moderate learning difficulties and ataxia.
Family PKDF291: 4 affected females with primary amenorrhea and hypogonadotropic hypogonadism. 3/4 had rudimentary uterus and small ovaries, 1/4 had small uterus and normal sized ovaries. No learning disabilities, microcephaly, short stature, epilepsy or neurological deficiet in all affected females.
Family DEM4395: 1 affected male and 2 affected females. All females had normal periods but their hormone profiles were not investigated. Aside from hearing loss there were no other self reported medical problems.

PMID: 25956234. Consanguineous Saudi family with 1 affected male and 1 affected female. Both patients have hearing loss, growth retardation and mental retardation, spastic diplegia and mild-severe white matter loss. No seizures were described in the patients. There is a third sibling (8 months) with the same variant; however, he did not show any of the phenotypes seen in his siblings but he is under regular checkups from a clinical team.

PMID:26970254. Consanguineous family of Arabic descent. Proband with 4 unaffected siblings and parents. Proband has hearing loss, azoospermia, no neurological symptoms other than the foot drop (neurophysiology revealed a sensory-motor demyelinative axonal peripheral neuropathy of the lower limbs). Father has cerebellar ataxia (cause unknown).

PMID: 27087618. Non-consanguineous Turkish family; however, parents are from the same village. 2 affected siblings (1 male, 1 female). Sister has secondary amenorrhea, hearing loss, no ovaries detected, hypogonadotropic hypogonadism, no neurological problems. Brother has hearing loss but no other problems.

PMID: 27650058. Consanguineous Algerian family with 2 affected females. Both have hearing loss and secondary amenorrhea, but no other neurological symptoms.

PMID: 27899912. 3 affected families (1 - 3), with 5 affected individuals (all males). All had congenital deafness, psychomotor retardation, white matter phenotype and short stature. Patients were not tested for infertility.
White matter disorders and cerebral calcification - narrow panel v1.146 APOPT1 Arina Puzriakova reviewed gene: APOPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25175347; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 17, OMIM:619061; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.145 LAMB1 Arina Puzriakova reviewed gene: LAMB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23472759, 25925986, 29888467; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.142 RPIA Arina Puzriakova Added comment: Comment on list classification: Cerebral white matter abnormalities identified in all cases to date (at least 4 unrelated families) - sufficient for RPIA to be rated Green on this panel
White matter disorders and cerebral calcification - narrow panel v1.126 HSPD1 Ivone Leong Mode of inheritance for gene: HSPD1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.124 HSPD1 Ivone Leong Phenotypes for gene: HSPD1 were changed from Leukodystrophy, hypomyelinating, 4, OMIM:612233; Spastic paraplegia 13, autosomal dominant, OMIM:605280 to Leukodystrophy, hypomyelinating, 4, OMIM:612233
White matter disorders and cerebral calcification - narrow panel v1.121 RAB11B Arina Puzriakova reviewed gene: RAB11B: Rating: GREEN; Mode of pathogenicity: None; Publications: 29106825; Phenotypes: Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter, OMIM:617807; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
White matter disorders and cerebral calcification - narrow panel v1.120 HSPD1 Ivone Leong Phenotypes for gene: HSPD1 were changed from Leukodystrophy, hypomyelinating, 4, 612233; Spastic paraplegia 13, autosomal dominant, 605280 to Leukodystrophy, hypomyelinating, 4, OMIM:612233; Spastic paraplegia 13, autosomal dominant, OMIM:605280
White matter disorders and cerebral calcification - narrow panel v1.118 HIKESHI Ivone Leong Added comment: Comment on publications: PMID: 26545878. 3 unrelated cases (6 individuals), Ashkenazi Jewish families. p.Val54Leu. 4/4 (2 MRI was not reported) delayed myelination and periventricular white matter abnormalities on brain imaging, 5/6 feeding difficulties, 5/6 developmental delay, 5/5 progressively decreasing head circumference percentile (up to -2 SD), 6/6 spasticity, 5/6 increased muscle tone, 1/6 ataxia, 2/6 (same family) optic atrophy, 4/6 nystagmus, 1/6 heart failure, 1/6 perimyocarditis.

PMID: 28000699. Finnish case. Difference variant than what was described in PMID:26545878 (p.Cys4Ser). Diffuse hypomyelination, cystic changes of periventricular white matter, has increased muscle tone, spasticity, ataxia, mild optic atrophy, myopia nystagmus and epilepsy. No feeding difficulties or microcephaly.
White matter disorders and cerebral calcification - narrow panel v1.115 NFU1 Arina Puzriakova Added comment: Comment on list classification: Overall there are sufficient unrelated cases (>3) with white matter abnormalities to rate this gene as Green on this panel.
White matter disorders and cerebral calcification - narrow panel v1.114 NFU1 Arina Puzriakova reviewed gene: NFU1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22077971, 28470589, 29441221, 31516295, 32747156, 32669393; Phenotypes: Multiple mitochondrial dysfunctions syndrome 1, OMIM:605711, Leukoencephalopathy, HP:0002352; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.105 NAXE Arina Puzriakova reviewed gene: NAXE: Rating: GREEN; Mode of pathogenicity: None; Publications: Encephalopathy, progressive, early-onset, with brain oedema and/or leukoencephalopathy, OMIM:617186; Phenotypes: 27616477, 27122014, 27290639, 30022751, 31758406, 31745726; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.89 KIAA1161 Ivone Leong Phenotypes for gene: KIAA1161 were changed from to Basal ganglia calcification, idiopathic, 7, autosomal recessive, OMIM:618317
White matter disorders and cerebral calcification - narrow panel v1.88 ERCC5 Eleanor Williams Added comment: Comment on list classification: Leaving rating as green but with a recommendation for amber or red rating following GMS review. As Expert reviewer reports there is no specific white matter abnormalities/leukodystrphy reported in the cases to date.
White matter disorders and cerebral calcification - narrow panel v1.85 ERCC5 Eleanor Williams reviewed gene: ERCC5: Rating: AMBER; Mode of pathogenicity: None; Publications: 8818951, 9096355, 24700531, 11228268, 8317483; Phenotypes: Cerebrooculofacioskeletal syndrome 3 OMIM:616570, Xeroderma pigmentosum, group G/Cockayne syndrome OMIM:278780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.82 ERCC4 Eleanor Williams reviewed gene: ERCC4: Rating: AMBER; Mode of pathogenicity: None; Publications: 23623389, 29105242; Phenotypes: Xeroderma pigmentosum, type F/Cockayne syndrome, OMIM:278760, XFE progeroid syndrome, OMIM:610965; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.79 ERCC3 Eleanor Williams reviewed gene: ERCC3: Rating: RED; Mode of pathogenicity: None; Publications: 9012405, 2167179, 16947863, 8408834, 8304337; Phenotypes: Trichothiodystrophy 2, photosensitive, OMIM:616390, Xeroderma pigmentosum, group B, OMIM:610651; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.76 ZFYVE26 Ivone Leong Phenotypes for gene: ZFYVE26 were changed from Spastic paraplegia 15, autosomal recessive, MIM#270700 to Spastic paraplegia 15, autosomal recessive, OMIM:270700
White matter disorders and cerebral calcification - narrow panel v1.73 WARS2 Ivone Leong Phenotypes for gene: WARS2 were changed from Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, MIM# 617710 to Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, OMIM:617710
White matter disorders and cerebral calcification - narrow panel v1.72 LSM7 Zornitza Stark gene: LSM7 was added
gene: LSM7 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Mode of inheritance for gene: LSM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSM7 were set to https://doi.org/10.1016/j.xhgg.2021.100034
Phenotypes for gene: LSM7 were set to Leukodystrophy; fetal death
Review for gene: LSM7 was set to RED
Added comment: Homozygous variant (p.Asp41Asn) identified in a child with leukodystrophy and a homozygous variant (p.Arg69Pro) identified in an individual that died in utero. In vitro and in vivo (zebrafish) assays supporting pathogenicity of the 2 variants.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v1.72 POLR3K Zornitza Stark gene: POLR3K was added
gene: POLR3K was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Mode of inheritance for gene: POLR3K was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3K were set to 30584594; 33659930
Phenotypes for gene: POLR3K were set to Hypomyelinating leukodystrophy-21, MIM#619310
Review for gene: POLR3K was set to AMBER
Added comment: Two individuals from same ethnic background reported with a common homozygous missense variant in this gene, suggestive of founder effect. Some functional evidence, and note other gene family members are linked to similar phenotypes.

Neurodegenerative phenotype: global developmental delay apparent from infancy with loss of motor, speech, and cognitive milestones in the first decades of life.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v1.72 LIG3 Zornitza Stark gene: LIG3 was added
gene: LIG3 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Mode of inheritance for gene: LIG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIG3 were set to 33855352
Phenotypes for gene: LIG3 were set to gut dysmotility; spasticity; ataxia; repetitive behaviours; neurogenic bladder; macular degeneration; leukoencephalopathy; cerebellar atrophy
Review for gene: LIG3 was set to GREEN
Added comment: Seven individuals from three unrelated families and functional data, variable ages of onset from early childhood to late adolescence.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v1.72 ERCC2 Eleanor Williams Added comment: Comment on list classification: Leaving rating as green, but with a recommendation of an amber rating following GMS review. Only one case reported with a white matter abnormality.
White matter disorders and cerebral calcification - narrow panel v1.56 ERCC1 Eleanor Williams changed review comment from: 4 patients reported with biallelic variants in ERCC1. In two cases there were developmental symptoms from birth. In the third neurodegenerative symptoms became apparent at age 15. And in the 4th family liver dysfunction was reported from a young age. No specific mention of white matter abnormalities.

PMID: 17273966 - Jaspers et al 2007 - report a child (165TOR) with cerebro-oculo-facio-skeletal syndrome showing relatively mild impairment of Nucleotide excision repair (NER) but very severe developmental symptoms and death in early infancy. Compound heterozygous variants in ERCC1 were found (one nonsense and and one missense) each inherited from one parent. NMR showed simplified gyral pattern and cerebellar hypoplasia. NO specific white matter abnormalites are reported.

PMID: 23623389 - Kashiyama et al 2013 - through targeted sequencing of ERCC1 and ERCC4 they report 1 patient with a homozygous missense variant. The child was diagnosed with Cockayne syndrome type II. Brain MRI at birth indicated a possible polymicrogyria; a NMR scan at 4 months of age showed large bilateral subdurals but no major visible malformations; at 9 months an abnormal electroencephalogram was recorded.

Imoto K, Boyle J, Oh K, Khan S, Ueda T, Nadem C, Slor H, Orgal S, Gadoth N, Busch D, Jaspers NG, Tamura D, JJ DiGiovanna, Kraemer KH. Patients with defects in the interacting nucleotide excision repair proteins ERCC1 or XPF show xeroderma pigmentosum with late onset severe neurological degeneration. J Invest Dermatol. 2007;127 Supp. 92 - conference abstract - can't access. Review by Gregg et al 2011 (PMID: 21612988) report that this abstract describes a patient with compound het variants in ERCC1 (nonsense mutation and a splicing mutation). The patient showed progressive neurodegeneration from age 15 resulting in dementia and cortical atrophy.

PMID: 33315086 - Apelt et al 2020 - describe 2 siblings with bi-allelic ERCC1 mutations (a missense and a deletion of exon 4) and a unique phenotype of short stature, photosensitivity, progressive cholestatic liver disease, and renal tubulopathy. Mild intellectual disability is reported. Brain magnetic resonance imaging (MRI) at 10 and 12 years for the respective siblings showed mild cerebral atrophy with moderate cerebellar atrophy, and mild brainstem atrophy in one sibling. ; to: 4 patients reported with biallelic variants in ERCC1. In two cases there were developmental symptoms from birth. In the third neurodegenerative symptoms became apparent at age 15. And in the 4th family liver dysfunction was reported from a young age. No specific mention of white matter abnormalities.

PMID: 17273966 - Jaspers et al 2007 - report a child (165TOR) with cerebro-oculo-facio-skeletal syndrome showing relatively mild impairment of Nucleotide excision repair (NER) but very severe developmental symptoms and death in early infancy. Compound heterozygous variants in ERCC1 were found (one nonsense and and one missense) each inherited from one parent. NMR showed simplified gyral pattern and cerebellar hypoplasia. NO specific white matter abnormalites are reported.

PMID: 23623389 - Kashiyama et al 2013 - through targeted sequencing of ERCC1 and ERCC4 they report 1 patient with a homozygous missense variant. The child (CS20LO) was diagnosed with Cockayne syndrome type II. Brain MRI at birth indicated a possible polymicrogyria; a NMR scan at 4 months of age showed large bilateral subdurals but no major visible malformations; at 9 months an abnormal electroencephalogram was recorded.

Imoto K, Boyle J, Oh K, Khan S, Ueda T, Nadem C, Slor H, Orgal S, Gadoth N, Busch D, Jaspers NG, Tamura D, JJ DiGiovanna, Kraemer KH. Patients with defects in the interacting nucleotide excision repair proteins ERCC1 or XPF show xeroderma pigmentosum with late onset severe neurological degeneration. J Invest Dermatol. 2007;127 Supp. 92 - conference abstract - can't access. Review by Gregg et al 2011 (PMID: 21612988) report that this abstract describes a patient with compound het variants in ERCC1 (nonsense mutation and a splicing mutation). The patient showed progressive neurodegeneration from age 15 resulting in dementia and cortical atrophy.

PMID: 33315086 - Apelt et al 2020 - describe 2 siblings with bi-allelic ERCC1 mutations (a missense and a deletion of exon 4) and a unique phenotype of short stature, photosensitivity, progressive cholestatic liver disease, and renal tubulopathy. Mild intellectual disability is reported. Brain magnetic resonance imaging (MRI) at 10 and 12 years for the respective siblings showed mild cerebral atrophy with moderate cerebellar atrophy, and mild brainstem atrophy in one sibling.
White matter disorders and cerebral calcification - narrow panel v1.55 ERCC1 Eleanor Williams changed review comment from: 3 patients reported with biallelic variants in ERCC1. In two cases there were developmental symptoms from birth. In the third neurodegenerative symptoms became apparent at age 15. No specific mention of white matter abnormalities.

PMID: 17273966 - Jaspers et al 2007 - report a child (165TOR) with cerebro-oculo-facio-skeletal syndrome showing relatively mild impairment of Nucleotide excision repair (NER) but very severe developmental symptoms and death in early infancy. Compound heterozygous variants in ERCC1 were found (one nonsense and and one missense) each inherited from one parent. NMR showed simplified gyral pattern and cerebellar hypoplasia. NO specific white matter abnormalites are reported.

PMID: 23623389 - Kashiyama et al 2013 - through targeted sequencing of ERCC1 and ERCC4 they report 1 patient with a homozygous missense variant. The child was diagnosed with Cockayne syndrome type II. Brain MRI at birth indicated a possible polymicrogyria; a NMR scan at 4 months of age showed large bilateral subdurals but no major visible malformations; at 9 months an abnormal electroencephalogram was recorded.

Imoto K, Boyle J, Oh K, Khan S, Ueda T, Nadem C, Slor H, Orgal S, Gadoth N, Busch D, Jaspers NG, Tamura D, JJ DiGiovanna, Kraemer KH. Patients with defects in the interacting nucleotide excision repair proteins ERCC1 or XPF show xeroderma pigmentosum with late onset severe neurological degeneration. J Invest Dermatol. 2007;127 Supp. 92 - can't access paper. Not in PubMed but review by Gregg et al 2011 (PMID: 21612988) report that it describes a patient with compound het variants in ERCC1 (nonsense mutation and a splicing mutation). The patient showed progressive neurodegeneration from age 15 resulting in dementia and cortical atrophy.; to: 4 patients reported with biallelic variants in ERCC1. In two cases there were developmental symptoms from birth. In the third neurodegenerative symptoms became apparent at age 15. And in the 4th family liver dysfunction was reported from a young age. No specific mention of white matter abnormalities.

PMID: 17273966 - Jaspers et al 2007 - report a child (165TOR) with cerebro-oculo-facio-skeletal syndrome showing relatively mild impairment of Nucleotide excision repair (NER) but very severe developmental symptoms and death in early infancy. Compound heterozygous variants in ERCC1 were found (one nonsense and and one missense) each inherited from one parent. NMR showed simplified gyral pattern and cerebellar hypoplasia. NO specific white matter abnormalites are reported.

PMID: 23623389 - Kashiyama et al 2013 - through targeted sequencing of ERCC1 and ERCC4 they report 1 patient with a homozygous missense variant. The child was diagnosed with Cockayne syndrome type II. Brain MRI at birth indicated a possible polymicrogyria; a NMR scan at 4 months of age showed large bilateral subdurals but no major visible malformations; at 9 months an abnormal electroencephalogram was recorded.

Imoto K, Boyle J, Oh K, Khan S, Ueda T, Nadem C, Slor H, Orgal S, Gadoth N, Busch D, Jaspers NG, Tamura D, JJ DiGiovanna, Kraemer KH. Patients with defects in the interacting nucleotide excision repair proteins ERCC1 or XPF show xeroderma pigmentosum with late onset severe neurological degeneration. J Invest Dermatol. 2007;127 Supp. 92 - conference abstract - can't access. Review by Gregg et al 2011 (PMID: 21612988) report that this abstract describes a patient with compound het variants in ERCC1 (nonsense mutation and a splicing mutation). The patient showed progressive neurodegeneration from age 15 resulting in dementia and cortical atrophy.

PMID: 33315086 - Apelt et al 2020 - describe 2 siblings with bi-allelic ERCC1 mutations (a missense and a deletion of exon 4) and a unique phenotype of short stature, photosensitivity, progressive cholestatic liver disease, and renal tubulopathy. Mild intellectual disability is reported. Brain magnetic resonance imaging (MRI) at 10 and 12 years for the respective siblings showed mild cerebral atrophy with moderate cerebellar atrophy, and mild brainstem atrophy in one sibling.
White matter disorders and cerebral calcification - narrow panel v1.53 ERCC1 Eleanor Williams edited their review of gene: ERCC1: Added comment: 3 patients reported with biallelic variants in ERCC1. In two cases there were developmental symptoms from birth. In the third neurodegenerative symptoms became apparent at age 15. No specific mention of white matter abnormalities.

PMID: 17273966 - Jaspers et al 2007 - report a child (165TOR) with cerebro-oculo-facio-skeletal syndrome showing relatively mild impairment of Nucleotide excision repair (NER) but very severe developmental symptoms and death in early infancy. Compound heterozygous variants in ERCC1 were found (one nonsense and and one missense) each inherited from one parent. NMR showed simplified gyral pattern and cerebellar hypoplasia. NO specific white matter abnormalites are reported.

PMID: 23623389 - Kashiyama et al 2013 - through targeted sequencing of ERCC1 and ERCC4 they report 1 patient with a homozygous missense variant. The child was diagnosed with Cockayne syndrome type II. Brain MRI at birth indicated a possible polymicrogyria; a NMR scan at 4 months of age showed large bilateral subdurals but no major visible malformations; at 9 months an abnormal electroencephalogram was recorded.

Imoto K, Boyle J, Oh K, Khan S, Ueda T, Nadem C, Slor H, Orgal S, Gadoth N, Busch D, Jaspers NG, Tamura D, JJ DiGiovanna, Kraemer KH. Patients with defects in the interacting nucleotide excision repair proteins ERCC1 or XPF show xeroderma pigmentosum with late onset severe neurological degeneration. J Invest Dermatol. 2007;127 Supp. 92 - can't access paper. Not in PubMed but review by Gregg et al 2011 (PMID: 21612988) report that it describes a patient with compound het variants in ERCC1 (nonsense mutation and a splicing mutation). The patient showed progressive neurodegeneration from age 15 resulting in dementia and cortical atrophy.; Changed rating: AMBER; Changed publications: 17273966, 23623389, 21612988; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.50 EPRS Eleanor Williams edited their review of gene: EPRS: Added comment: As reported by the expert reviewer PMID: 29576217 (Mendes et al 2018) reports 4 unrelated affected individuals with hypomyelination and biallelic (homozygous or compound het) pathogenic variants in EPRS. 5 variants in total identified (1 nonsense, 1 frameshift, 3 missense). Variants segregated with the disease in all 4 families. All 4 presented initially before the age of 18 and in all brain MRI showed a hypomyelinating leukodystrophy with thinning of the corpus callosum. In 3 cases the variant was identified by WES, in one by direct sequencing of EPRS1.

PMID: 33805425 - Sawaguchi et al 2021 - using a mouse model they show that EPRS1 variant Arg339-to-Ter (R339X) (found in one of the patients in Mendes et al in heterozgyous state with another variant) localizes EPRS1 proteins as polymeric aggregates into Rab7-positive vesicle structures in mouse oligodendroglial FBD-102b cells. Wild-type proteins are distributed throughout the cell bodies. This seems to inhibit cell morphological differentiation.; Changed rating: GREEN; Changed publications: 29576217, 33805425; Changed phenotypes: Leukodystrophy, hypomyelinating, 15, OMIM:617951; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.47 DEGS1 Eleanor Williams reviewed gene: DEGS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30620338, 30620337, 31186544; Phenotypes: Leukodystrophy, hypomyelinating, 18, OMIM:618404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.44 DCAF17 Eleanor Williams reviewed gene: DCAF17: Rating: ; Mode of pathogenicity: None; Publications: 19026396, 20507343, 30409855; Phenotypes: Woodhouse-Sakati syndrome OMIM:241080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.39 ACBD5 Arina Puzriakova reviewed gene: ACBD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23105016, 27799409, 33427402; Phenotypes: Retinal dystrophy with leukodystrophy, OMIM:618863; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.38 CLDN11 Zornitza Stark gene: CLDN11 was added
gene: CLDN11 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Mode of inheritance for gene: CLDN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN11 were set to 33313762
Phenotypes for gene: CLDN11 were set to Hypomyelinating leukodystrophy
Review for gene: CLDN11 was set to GREEN
gene: CLDN11 was marked as current diagnostic
Added comment: In three unrelated individuals with early-onset spastic movement disorder, expressive speech disorder and eye abnormalities including hypermetropia, 2 different heterozygous de novo stop-loss variants were identified. One of the variants did not lead to a loss of CLDN11 expression on RNA level in fibroblasts indicating this transcript is not subject to nonsense-mediated decay and most likely translated into an extended protein.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v1.38 FA2H Sarah Leigh Phenotypes for gene: FA2H were changed from to Spastic paraplegia 35, autosomal recessive OMIM:612319; hereditary spastic paraplegia 35 MONDO:0012866
White matter disorders and cerebral calcification - narrow panel v1.33 COA7 Sarah Leigh Phenotypes for gene: COA7 were changed from Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MIM#618387 to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 OMIM:618387; spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MONDO:0020770
White matter disorders and cerebral calcification - narrow panel v1.32 RNU7-1 Arina Puzriakova Added comment: Comment on list classification: Rating Amber but should be promoted to Green at the next GMS panel update (added 'for-review' tag) - extensive intracranial calcification and white matter abnormalities were a commonly reported feature in patients with biallelic variants in this gene (PMID:33230297)
White matter disorders and cerebral calcification - narrow panel v1.31 RNU7-1 Arina Puzriakova gene: RNU7-1 was added
gene: RNU7-1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
for-review tags were added to gene: RNU7-1.
Mode of inheritance for gene: RNU7-1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU7-1 were set to 33230297
Phenotypes for gene: RNU7-1 were set to Aicardi–Goutières syndrome-like; Type I interferonopathy
Review for gene: RNU7-1 was set to GREEN
Added comment: Not associated with any phenotype in OMIM or Gene2Phenotype.

- PMID: 33230297 (2020) - 16 individuals from 11 families with biallelic variants in the RNU7-1 gene. Clinical features were typical of Aicardi–Goutières syndrome, including spasticity, dystonia, epilepsy, peripheral neuropathy, brain calcification, mild skin involvement and delayed psychomotor development. Upregulated interferon signalling was detected in patient blood and fibroblasts. 4/12 variants were observed in 2 or more families - several from different ethnic backgrounds. 8 variants are recorded in gnomAD but at a frequency of ≤0.005, and no biallelic variants were identified in control populations. Some functional data showing a disturbance of histone RNA processing in patient-derived compared to control fibroblasts.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v1.30 AP4B1 Arina Puzriakova Phenotypes for gene: AP4B1 were changed from Spastic paraplegia 47, autosomal recessive MIM#614066 to Spastic paraplegia 47, autosomal recessive, OMIM:614066; Hereditary spastic paraplegia 47, MONDO:0013551
White matter disorders and cerebral calcification - narrow panel v1.26 STN1 Sarah Leigh edited their review of gene: STN1: Added comment: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least four variants reported in three unrelated cases, together with a supportive zebrafish model and other functional studies.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.20 TMEM106B Arina Puzriakova reviewed gene: TMEM106B: Rating: GREEN; Mode of pathogenicity: None; Publications: 29186371, 29444210, 30643851, 32595021; Phenotypes: Leukodystrophy, hypomyelinating, 16 OMIM:617964; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
White matter disorders and cerebral calcification - narrow panel v1.20 STN1 Zornitza Stark gene: STN1 was added
gene: STN1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Mode of inheritance for gene: STN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STN1 were set to 27432940; 32627942
Phenotypes for gene: STN1 were set to Cerebroretinal microangiopathy with calcifications and cysts 2, MIM# 617341
Review for gene: STN1 was set to GREEN
Added comment: Three individuals from unrelated families described with a multisystem disorder characterized by premature aging, pancytopaenia, hypocellular bone marrow, osteopenia, liver fibrosis, and vascular telangiectasia resulting in gastrointestinal bleeding, as well as intracranial calcifications and leukodystrophy, resulting in spasticity, ataxia, or dystonia. Gene belongs on multiple panels.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v1.20 ACER3 Zornitza Stark gene: ACER3 was added
gene: ACER3 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Mode of inheritance for gene: ACER3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACER3 were set to 32816236; 26792856
Phenotypes for gene: ACER3 were set to Leukodystrophy
Review for gene: ACER3 was set to AMBER
Added comment: Two families reported with bi-allelic variants, and paediatric onset progressive leukodystorphy. Functional data demonstrating ACER3 deficiency.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v1.20 SCAF4 Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to rate this gene Green at the next GMS panel update - sufficient number of unrelated cases presenting white matter anomalies associated with distinct variants in SCAF4
White matter disorders and cerebral calcification - narrow panel v1.19 SCAF4 Arina Puzriakova gene: SCAF4 was added
gene: SCAF4 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
for-review tags were added to gene: SCAF4.
Mode of inheritance for gene: SCAF4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SCAF4 were set to 32730804
Phenotypes for gene: SCAF4 were set to SCAF4-related Neurodevelopmental Disorder; Intellectual disability; Seizures; Behavioural abnormalities
Review for gene: SCAF4 was set to GREEN
Added comment: Currently not associated with any phenotype in OMIM (last edited on 23/09/2014), but is a probable gene SCAF4-related Neurodevelopmental Disorder in Gen2Phen.

PMID: 32730804 (2020) - At least 8 unrelated patients with likely pathogenic variants in SCAF4 and mild DD/ID, seizures behavioural abnormalities, and various skeletal, renal and cardiac anomalies. 7 de novo and 1 inherited variant. Brain MRIs were performed in five individuals
showing nonspecific white matter anomalies in three of them. One other individual was diagnosed with pontocerebellar hypoplasia and a thin corpus callosum.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v1.18 USP18 Arina Puzriakova reviewed gene: USP18: Rating: GREEN; Mode of pathogenicity: None; Publications: 12833411, 27325888, 31940699; Phenotypes: Pseudo-TORCH syndrome 2, 617397; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.16 KIAA1161 Zornitza Stark gene: KIAA1161 was added
gene: KIAA1161 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Mode of inheritance for gene: KIAA1161 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KIAA1161 were set to 30656188; 30649222; 30460687; 29910000; 31951047
Review for gene: KIAA1161 was set to GREEN
Added comment: PMID 31951047: In a cohort study comprising 435 individuals with primary brain calcification, 38 individuals identified with mono-allelic variants in this gene, in addition to 14 with bi-allelic variants. Clinical and imaging penetrance of individuals with bi-allelic variants were 100%, whereas among individuals with heterozygous variants, penetrance of imaging phenotype was reduced to 73.7% (28 of 38) and clinical penetrance was much lower. Most (34 of 38) remained asymptomatic whereas 4 had symptoms of uncertain clinical significance (nonspecific depression, epilepsy and late-onset parkinsonism). Compared with individuals with biallelic MYORG variants, individuals with heterozygous variants had brain calcifications with much lower calcification scores (P < 2e-16). HGNC approved name is MYORG.

Note additional publications supporting association with bi-allelic variants.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v1.16 FARSA Zornitza Stark gene: FARSA was added
gene: FARSA was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Mode of inheritance for gene: FARSA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FARSA were set to 31355908
Phenotypes for gene: FARSA were set to Rajab interstitial lung disease with brain calcifications 2, MIM# 619013
Review for gene: FARSA was set to RED
Added comment: Autosomal recessive disorder characterized by growth delay, interstitial lung disease, liver disease, and abnormal brain MRI findings, including brain calcifications and periventricular cysts. Single affected individual reported, but FARSA interacts with FARSB, which causes a similar disorder.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v1.16 NUP188 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to rate this gene Green at the next major review - abnormalities on brain MRI are reported in all affected individuals to date, including loss of white matter (4/8) and delayed myelination (5/8)
White matter disorders and cerebral calcification - narrow panel v1.15 NUP188 Arina Puzriakova gene: NUP188 was added
gene: NUP188 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
for-review tags were added to gene: NUP188.
Mode of inheritance for gene: NUP188 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP188 were set to 32021605; 32275884
Phenotypes for gene: NUP188 were set to Sandestig-Stefanova syndrome, 618804
Review for gene: NUP188 was set to GREEN
Added comment: Associated with Sandestig-Stefanova syndrome in OMIM, but not yet in G2P.

- PMID: 32021605 (2020) - Two unrelated patients with different homozygous nonsense variants of NUP188, c.287dupA, p.Tyr96* and c.337C>T, p.Gln113*, respectively. Authors note strikingly comparable phenotypes including pre- and postnatal microcephaly, trigonocephaly, congenital cataract, microphthalmia, cleft lip and palate or high-arched palate, camptodactyly, ventricular septal defect, and brain MRI anomalies (ventriculomegaly, loss of periventricular white matter, thin corpus callosum, and delayed myelination). Both ultimately died as a result of central respiratory failure at the age of 67 and 140 days, respectively.

- PMID: 32275884 (2020) - Six individuals from four unrelated families with bi-allelic truncating variants in NUP188 and similar phenotypes characterised by prenatal-onset ventriculomegaly or suspected brain malformation (4/6), congenital cataracts (4/6), congenital heart defects (5/5), hypotonia (5/6), brain MRI abnormalities (6/6) including ventriculomegaly loss of white-matter, hypoplastic corpus callosum, and delayed myelination. Progressive microcephaly consistent with a neurodegenerative process was noted in at least 3 cases. All six patients died of respiratory failure or respiratory-related illness: five within the first seven months of life; and the sixth at 2 years and 7 months, who also has severe ID and was non-ambulatory.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v1.14 VPS11 Zornitza Stark reviewed gene: VPS11: Rating: GREEN; Mode of pathogenicity: None; Publications: 27120463, 26307567, 27473128; Phenotypes: Leukodystrophy, hypomyelinating, 12, MIM# 616683; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 WARS2 Zornitza Stark gene: WARS2 was added
gene: WARS2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: WARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WARS2 were set to 31282308; 28650581; 30920170
Phenotypes for gene: WARS2 were set to Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, MIM# 617710
Review for gene: WARS2 was set to GREEN
gene: WARS2 was marked as current diagnostic
Added comment: At least three affected individuals where white matter changes were a prominent feature of the phenotype.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 ZFYVE26 Zornitza Stark reviewed gene: ZFYVE26: Rating: GREEN; Mode of pathogenicity: None; Publications: 19084844; Phenotypes: Spastic paraplegia 15, autosomal recessive, MIM# 270700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 UFM1 Zornitza Stark gene: UFM1 was added
gene: UFM1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: UFM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UFM1 were set to 28931644; 29868776
Phenotypes for gene: UFM1 were set to Leukodystrophy, hypomyelinating, 14, MIM# 617899
Review for gene: UFM1 was set to GREEN
gene: UFM1 was marked as current diagnostic
Added comment: 16 children from Roma descent reported initially, all had homozygous 3bp deletion in the promoter of UFM1 (founder). Another 4 individuals from 2 Sudanese families reported subsequently, with missense variant in gene.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 TUFM Zornitza Stark reviewed gene: TUFM: Rating: GREEN; Mode of pathogenicity: None; Publications: 28132884, 26741492, 17160893; Phenotypes: Combined oxidative phosphorylation deficiency 4, MIM# 610678, Mitochondrial Leukoencephalopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
White matter disorders and cerebral calcification - narrow panel v1.14 TMEM63A Zornitza Stark gene: TMEM63A was added
gene: TMEM63A was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: TMEM63A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM63A were set to 31587869
Phenotypes for gene: TMEM63A were set to Leukodystrophy, hypomyelinating, 19, transient infantile, MIM# 618688
Review for gene: TMEM63A was set to GREEN
Added comment: 4 unrelated patients with infantile-onset leukodystrophy with heterozygous variants, three of which were de novo.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 TMEM106B Zornitza Stark reviewed gene: TMEM106B: Rating: GREEN; Mode of pathogenicity: None; Publications: 29186371, 29444210, 28728022, 30643851; Phenotypes: Leukodystrophy, hypomyelinating, 16 617964; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
White matter disorders and cerebral calcification - narrow panel v1.14 SPG11 Zornitza Stark reviewed gene: SPG11: Rating: GREEN; Mode of pathogenicity: None; Publications: 18067136; Phenotypes: Spastic paraplegia 11, autosomal recessive, MIM# 604360; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 SPART Zornitza Stark reviewed gene: SPART: Rating: GREEN; Mode of pathogenicity: None; Publications: 28875386, 15372254; Phenotypes: Troyer syndrome 275900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 SNORD118 Zornitza Stark reviewed gene: SNORD118: Rating: GREEN; Mode of pathogenicity: None; Publications: 27571260; Phenotypes: Leukoencephalopathy, brain calcifications, and cysts 614561; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 SDHA Zornitza Stark reviewed gene: SDHA: Rating: GREEN; Mode of pathogenicity: None; Publications: 22972948; Phenotypes: Mitochondrial respiratory chain complex II deficiency, MIM#252011; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 RPIA Zornitza Stark gene: RPIA was added
gene: RPIA was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: RPIA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPIA were set to 31247379; 14988808; 31056085
Phenotypes for gene: RPIA were set to Ribose 5-phosphate isomerase deficiency, MIM# 608611
Review for gene: RPIA was set to GREEN
Added comment: Four unrelated individuals described to date, variable onset of leukodystrophy in childhood/adolescence, though other symptoms generally precede.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 RAB11B Zornitza Stark reviewed gene: RAB11B: Rating: GREEN; Mode of pathogenicity: None; Publications: 29106825; Phenotypes: Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter 617807; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
White matter disorders and cerebral calcification - narrow panel v1.14 PTEN Zornitza Stark gene: PTEN was added
gene: PTEN was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: PTEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTEN were set to 29720545; 29152901; 30664625
Phenotypes for gene: PTEN were set to Cowden syndrome 1, MIM# 158350
Review for gene: PTEN was set to GREEN
gene: PTEN was marked as current diagnostic
Added comment: White matter changes described in many individuals.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 POLH Zornitza Stark reviewed gene: POLH: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Xeroderma pigmentosum, variant type 278750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 NFU1 Zornitza Stark gene: NFU1 was added
gene: NFU1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: NFU1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFU1 were set to 21944046; 22077971; 32747156; 29441221
Phenotypes for gene: NFU1 were set to Multiple mitochondrial dysfunctions syndrome 1, MIM# 605711
Review for gene: NFU1 was set to GREEN
gene: NFU1 was marked as current diagnostic
Added comment: Bi-allelic variants in this gene cause multiple mitochondrial dysfunctions syndrome, a severe autosomal recessive disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, and early death. Cavitating leukodystrophy and other white matter changes described in multiple affected individuals.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 NAXE Zornitza Stark reviewed gene: NAXE: Rating: GREEN; Mode of pathogenicity: None; Publications: 27122014, 27616477, 31758406; Phenotypes: Encephalopathy, progressive, early-onset, with brain oedema and/or leukoencephalopathy, MIM# 617186; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 NAXD Zornitza Stark gene: NAXD was added
gene: NAXD was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: NAXD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAXD were set to 30576410
Phenotypes for gene: NAXD were set to Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2 MIM#618321
Review for gene: NAXD was set to GREEN
gene: NAXD was marked as current diagnostic
Added comment: Six unrelated families reported.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 MPLKIP Zornitza Stark reviewed gene: MPLKIP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Trichothiodystrophy 4, nonphotosensitive 234050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 KIF5A Zornitza Stark gene: KIF5A was added
gene: KIF5A was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: KIF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5A were set to 27463701; 27414745
Phenotypes for gene: KIF5A were set to Myoclonus, intractable, neonatal, MIM# 617235
Review for gene: KIF5A was set to GREEN
gene: KIF5A was marked as current diagnostic
Added comment: Variants in KIF5A cause a range of phenotypes with variable range of onset including spastic paraplegia and neuropathy. Three unrelated families reported with de novo frame-shifts in the C-terminal domain of KIF5A and neonatal intractable myoclonus, a severe neurologic disorder characterized by the onset of intractable myoclonic seizures soon after birth. Affected infants had intermittent apnea, abnormal eye movements, pallor of the optic nerve, and lack of developmental progress. Brain imaging showed a progressive leukoencephalopathy.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 ISCA2 Zornitza Stark reviewed gene: ISCA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25539947, 29297947, 29122497, 29359243; Phenotypes: Multiple mitochondrial dysfunctions syndrome 4, MIM# 616370; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 ISCA1 Zornitza Stark gene: ISCA1 was added
gene: ISCA1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: ISCA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ISCA1 were set to 28356563; 32092383; 31016283; 30113620; 30105122
Phenotypes for gene: ISCA1 were set to Multiple mitochondrial dysfunctions syndrome 5, MIM# 617613
Review for gene: ISCA1 was set to GREEN
gene: ISCA1 was marked as current diagnostic
Added comment: Multiple unrelated families reported. Severe disorder characterised by progressive neurologic deterioration beginning in early infancy. Affected individuals have essentially no psychomotor development and have early-onset seizures with neurologic decline and spasticity. Brain imaging shows severe leukodystrophy with evidence of dys- or delayed myelination. Rat model results in early lethality. Founder variant c.259G > A, p.(Glu87Lys) reported in Indian families.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 HSPD1 Zornitza Stark reviewed gene: HSPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18571143, 27405012, 32532876, 28377887, 27405012; Phenotypes: Leukodystrophy, hypomyelinating, 4, MIM# 612233; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
White matter disorders and cerebral calcification - narrow panel v1.14 HIKESHI Zornitza Stark gene: HIKESHI was added
gene: HIKESHI was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: HIKESHI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HIKESHI were set to 26545878
Phenotypes for gene: HIKESHI were set to Leukodystrophy, hypomyelinating, 13, MIM# 616881
Review for gene: HIKESHI was set to GREEN
gene: HIKESHI was marked as current diagnostic
Added comment: Six children from three unrelated Ashkenazi Jewish families reported, segregating same homozygous variant. Neurodegenerative disorder characterized by infantile onset of delayed psychomotor development, axial hypotonia, and spasticity associated with delayed myelination and periventricular white matter abnormalities on brain imaging. Other features: visual impairment; cardiac failure during acute illness.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 GTF2H5 Zornitza Stark reviewed gene: GTF2H5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Trichothiodystrophy 3, photosensitive 616395; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 GLRX5 Zornitza Stark gene: GLRX5 was added
gene: GLRX5 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: GLRX5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLRX5 were set to 24334290; 30770271
Phenotypes for gene: GLRX5 were set to Spasticity, childhood-onset, with hyperglycinemia, MIM# 616859
Review for gene: GLRX5 was set to GREEN
gene: GLRX5 was marked as current diagnostic
Added comment: PMID: 24334290 - 3 patients (3 families) with non-ketotic hyperglycinemia, supported by functional studies. Patients had normal development with childhood-onset spastic paraplegia (3/3), spinal lesion (1/3), optic atrophy (1/3) and brain signal abnormalities involving the frontal and parietal white matter (2/3)

PMID: 30770271 - 1 patient with childhood onset cavitating leukoencephalopathy.

p.Lys51del is a recurring variant.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 GLB1 Zornitza Stark gene: GLB1 was added
gene: GLB1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: GLB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLB1 were set to 25691190
Phenotypes for gene: GLB1 were set to GM1-gangliosidosis, type I, MIM# 230500; GM1-gangliosidosis, type II, MIM# 230600
Review for gene: GLB1 was set to GREEN
gene: GLB1 was marked as current diagnostic
Added comment: Well established gene-disease association, white matter changes are a feature.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 FIG4 Zornitza Stark gene: FIG4 was added
gene: FIG4 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: FIG4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FIG4 were set to 30740813; 29688489
Phenotypes for gene: FIG4 were set to Charcot-Marie-Tooth disease, type 4J 611228; Yunis-Varon syndrome 216340; leukoencephalopathy
Review for gene: FIG4 was set to GREEN
gene: FIG4 was marked as current diagnostic
Added comment: Four unrelated families reported with bi-allelic variants in this gene and a leukoencephalopathy phenotype. Mouse model recapitulates the phenotype. Please note gene is associated with multiple other phenotypes including Yunis-Varon syndrome, CMT, ALS
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 FA2H Zornitza Stark reviewed gene: FA2H: Rating: GREEN; Mode of pathogenicity: None; Publications: 31837835, 30446360, 22965561, 21592092; Phenotypes: Spastic paraplegia 35, autosomal recessive, MIM# 612319; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 ERCC5 Zornitza Stark reviewed gene: ERCC5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebrooculofacioskeletal syndrome 3 616570, Xeroderma pigmentosum, group G 278780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 ERCC4 Zornitza Stark reviewed gene: ERCC4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Xeroderma pigmentosum, group F, MIM# 278760; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 ERCC3 Zornitza Stark reviewed gene: ERCC3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Trichothiodystrophy 2, photosensitive 616390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 ERCC2 Zornitza Stark reviewed gene: ERCC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29451896; Phenotypes: Trichothiodystrophy 1, photosensitive 601675; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 ERCC1 Zornitza Stark reviewed gene: ERCC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebrooculofacioskeletal syndrome 4 610758; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 EPRS Zornitza Stark gene: EPRS was added
gene: EPRS was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: EPRS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPRS were set to 29576217
Phenotypes for gene: EPRS were set to Leukodystrophy, hypomyelinating, 15, MIM# 617951
Review for gene: EPRS was set to GREEN
gene: EPRS was marked as current diagnostic
Added comment: Four unrelated families reported with this neurodegenerative disorder. Onset of motor and cognitive impairment in the first or second decade of life. Features include dystonia, ataxia, spasticity, dysphagia, severe optic atrophy, and some have hearing loss. Brain imaging shows hypomyelinating leukodystrophy with thin corpus callosum.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 DEGS1 Zornitza Stark gene: DEGS1 was added
gene: DEGS1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: DEGS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DEGS1 were set to 30620338; 30620337
Phenotypes for gene: DEGS1 were set to Leukodystrophy, hypomyelinating, 18, MIM#618404
Review for gene: DEGS1 was set to GREEN
gene: DEGS1 was marked as current diagnostic
Added comment: 20 individuals from 14 unrelated families. Hypomyelinating leukodystorphy is the prominent feature of this condition.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 DCAF17 Zornitza Stark gene: DCAF17 was added
gene: DCAF17 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: DCAF17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DCAF17 were set to 19026396; 20507343
Phenotypes for gene: DCAF17 were set to Woodhouse-Sakati syndrome, MIM# 241080
Review for gene: DCAF17 was set to GREEN
gene: DCAF17 was marked as current diagnostic
Added comment: White matter changes are part of the phenotype.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 CYP7B1 Zornitza Stark reviewed gene: CYP7B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24117163, 19439420, 19187859; Phenotypes: Spastic paraplegia 5A, autosomal recessive, MIM# 270800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
White matter disorders and cerebral calcification - narrow panel v1.14 COA7 Zornitza Stark gene: COA7 was added
gene: COA7 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: COA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COA7 were set to 27683825; 29718187
Phenotypes for gene: COA7 were set to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MIM#618387
Review for gene: COA7 was set to GREEN
gene: COA7 was marked as current diagnostic
Added comment: At least 3 unrelated cases reported with leukoencephalopathy as a feature of the condition. Paediatric age of onset.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 CNTNAP1 Zornitza Stark reviewed gene: CNTNAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28374019, 29882456; Phenotypes: Hypomyelinating neuropathy, congenital, 3, MIM# 618186, Lethal congenital contracture syndrome 7, MIM# 616286; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.14 CLPP Zornitza Stark gene: CLPP was added
gene: CLPP was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: CLPP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLPP were set to 27899912
Phenotypes for gene: CLPP were set to Perrault syndrome 3, MIM# 614129
Review for gene: CLPP was set to GREEN
gene: CLPP was marked as current diagnostic
Added comment: Prominent white matter changes identified in at least three unrelated individuals.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 BOLA3 Zornitza Stark reviewed gene: BOLA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30302924, 29654549, 30302924; Phenotypes: Multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia, MIM# 614299; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
White matter disorders and cerebral calcification - narrow panel v1.14 APOPT1 Zornitza Stark gene: APOPT1 was added
gene: APOPT1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: APOPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APOPT1 were set to 25175347
Phenotypes for gene: APOPT1 were set to Mitochondrial complex IV deficiency, MIM# 220110
Review for gene: APOPT1 was set to GREEN
gene: APOPT1 was marked as current diagnostic
Added comment: Cavitating leukodystrophy reported as part of this mitochondrial disorder, onset described as late infancy/early childhood.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 AP4B1 Zornitza Stark gene: AP4B1 was added
gene: AP4B1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: AP4B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP4B1 were set to 29193663
Phenotypes for gene: AP4B1 were set to Spastic paraplegia 47, autosomal recessive MIM#614066
Review for gene: AP4B1 was set to GREEN
gene: AP4B1 was marked as current diagnostic
Added comment: White matter changes have been reported as a feature of the condition in at least ten unrelated cases with biallelic variants. The onset of the condition is in childhood.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 AIFM1 Zornitza Stark gene: AIFM1 was added
gene: AIFM1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: AIFM1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: AIFM1 were set to 28842795; 27102849
Phenotypes for gene: AIFM1 were set to Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy, MIM# 300232
Review for gene: AIFM1 was set to GREEN
Added comment: Seven unrelated families reported with X-linked spondyloepimetaphyseal dysplasia with hypomyelinating leukodystrophy (SEMDHL), an X-linked recessive developmental disorder characterised by slowly progressive skeletal and neurologic abnormalities, including short stature, large and deformed joints, significant motor impairment, visual defects, and sometimes cognitive deficits. Affected individuals typically have normal early development in the first year or so of life, followed by development regression and the development of symptoms. Brain imaging shows white matter abnormalities consistent with hypomyelinating leukodystrophy.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 AARS Zornitza Stark gene: AARS was added
gene: AARS was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list
Mode of inheritance for gene: AARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AARS were set to 28493438; 25817015
Phenotypes for gene: AARS were set to Epileptic encephalopathy, early infantile, 29, MIM# 616339
Review for gene: AARS was set to GREEN
gene: AARS was marked as current diagnostic
Added comment: Bi-allelic variants associated with a severe phenotype comprising leukodystrophy, epilepsy, microcephaly and neurodevelopmental delay reported in three families.
Sources: Expert list
White matter disorders and cerebral calcification - narrow panel v1.14 CNP Zornitza Stark gene: CNP was added
gene: CNP was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Mode of inheritance for gene: CNP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNP were set to 32128616; 12590258
Phenotypes for gene: CNP were set to Hypomyelinating leukodystrophy
Review for gene: CNP was set to AMBER
Added comment: Single consanguineous family described with homozygous missense in affected child (additional two affected deceased offspring unavailable for testing; healthy carrier parents and sibling).
Loss of protein by Western blot and defect in F-actin structure and organization observed in patient fibroblasts.
Deficiency of CNP in mouse has previously been shown to cause a lethal white matter neurodegenerative phenotype (PMID: 12590258), similar to the phenotype observed in this family.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v1.8 POLG2 Sarah Leigh Added comment: Comment on mode of inheritance: Reporting and characterization of a homozygous POLG2 variant in mitochondrial DNA depletion syndrome and in an autosomal recessive epilepsy family without ophthalmoplegia (PMID 27592148; 30157269; 31286721).
White matter disorders and cerebral calcification - narrow panel v1.8 POLG2 Sarah Leigh Mode of inheritance for gene: POLG2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v0.11 GJB1 Ellen McDonagh gene: GJB1 was added
gene: GJB1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: GJB1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: GJB1 were set to Charcot-Marie-Tooth neuropathy, X-linked dominant, 1
White matter disorders and cerebral calcification - narrow panel v0.11 POLG2 Ellen McDonagh gene: POLG2 was added
gene: POLG2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: POLG2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: POLG2 were set to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4
White matter disorders and cerebral calcification - narrow panel v0.11 SLC25A12 Ellen McDonagh gene: SLC25A12 was added
gene: SLC25A12 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SLC25A12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC25A12 were set to Hypomyelination, global cerebral
White matter disorders and cerebral calcification - narrow panel v0.11 SDHD Ellen McDonagh gene: SDHD was added
gene: SDHD was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: SDHD was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SDHD were set to Mitochondrial complex II deficiency
White matter disorders and cerebral calcification - narrow panel v0.11 SCP2 Ellen McDonagh gene: SCP2 was added
gene: SCP2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SCP2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SCP2 were set to Leukoencephalopathy with dystonia and motor neuropathy
White matter disorders and cerebral calcification - narrow panel v0.11 SCO2 Ellen McDonagh gene: SCO2 was added
gene: SCO2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SCO2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SCO2 were set to Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1
White matter disorders and cerebral calcification - narrow panel v0.11 SCO1 Ellen McDonagh gene: SCO1 was added
gene: SCO1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SCO1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SCO1 were set to Mitochondrial complex IV deficiency
White matter disorders and cerebral calcification - narrow panel v0.11 RNASET2 Ellen McDonagh gene: RNASET2 was added
gene: RNASET2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: RNASET2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RNASET2 were set to Leukoencephalopathy, cystic, without megalencephaly
White matter disorders and cerebral calcification - narrow panel v0.11 PSAP Ellen McDonagh gene: PSAP was added
gene: PSAP was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PSAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSAP were set to 249900
Phenotypes for gene: PSAP were set to Combined SAP deficiency
White matter disorders and cerebral calcification - narrow panel v0.11 POLR3A Ellen McDonagh gene: POLR3A was added
gene: POLR3A was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POLR3A were set to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism
White matter disorders and cerebral calcification - narrow panel v0.11 POLR1C Ellen McDonagh gene: POLR1C was added
gene: POLR1C was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: POLR1C was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POLR1C were set to Leukodystrophy, hypomyelinating, 11
White matter disorders and cerebral calcification - narrow panel v0.11 POLG Ellen McDonagh gene: POLG was added
gene: POLG was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: POLG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POLG were set to Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE); Mitochondrial DNA depletion syndrome 4A (Alpers type) 203700; Mitochondrial DNA depletion syndrome 4B (MNGIE type) 613662
White matter disorders and cerebral calcification - narrow panel v0.11 PEX19 Ellen McDonagh gene: PEX19 was added
gene: PEX19 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: PEX19 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX19 were set to Peroxisome biogenesis disorder 12A (Zellweger)
White matter disorders and cerebral calcification - narrow panel v0.11 NKX6-2 Ellen McDonagh gene: NKX6-2 was added
gene: NKX6-2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: NKX6-2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NKX6-2 were set to Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy
White matter disorders and cerebral calcification - narrow panel v0.11 NDUFAF3 Ellen McDonagh gene: NDUFAF3 was added
gene: NDUFAF3 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: NDUFAF3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFAF3 were set to Mitochondrial complex I deficiency
White matter disorders and cerebral calcification - narrow panel v0.11 MCOLN1 Ellen McDonagh gene: MCOLN1 was added
gene: MCOLN1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: MCOLN1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MCOLN1 were set to Mucolipidosis IV
White matter disorders and cerebral calcification - narrow panel v0.11 GALC Ellen McDonagh gene: GALC was added
gene: GALC was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: GALC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GALC were set to Krabbe disease
White matter disorders and cerebral calcification - narrow panel v0.11 FOLR1 Ellen McDonagh gene: FOLR1 was added
gene: FOLR1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: FOLR1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FOLR1 were set to Neurodegeneration due to cerebral folate transport deficiency
White matter disorders and cerebral calcification - narrow panel v0.11 DPYD Ellen McDonagh gene: DPYD was added
gene: DPYD was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: DPYD was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DPYD were set to Dihydropyrimidine dehydrogenase deficiency; 5-fluorouracil toxicity 274270
White matter disorders and cerebral calcification - narrow panel v0.11 DARS Ellen McDonagh gene: DARS was added
gene: DARS was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: DARS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DARS were set to Hypomyelination with brainstem and spinal cord involvement and leg spasticity
White matter disorders and cerebral calcification - narrow panel v0.11 ARSA Ellen McDonagh gene: ARSA was added
gene: ARSA was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ARSA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ARSA were set to Metachromatic leukodystrophy (Arylsulfatase A Deficiency)
White matter disorders and cerebral calcification - narrow panel v0.11 AIMP1 Ellen McDonagh gene: AIMP1 was added
gene: AIMP1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: AIMP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AIMP1 were set to Leukodystrophy, hypomyelinating, 3
White matter disorders and cerebral calcification - narrow panel v0.11 TUBB2B Ellen McDonagh gene: TUBB2B was added
gene: TUBB2B was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: TUBB2B was set to Unknown
Phenotypes for gene: TUBB2B were set to Cerebral Malformation Disorders
White matter disorders and cerebral calcification - narrow panel v0.11 TUBA8 Ellen McDonagh gene: TUBA8 was added
gene: TUBA8 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: TUBA8 was set to Unknown
Phenotypes for gene: TUBA8 were set to Cerebral Malformation Disorders
White matter disorders and cerebral calcification - narrow panel v0.11 NOTCH3 Ellen McDonagh gene: NOTCH3 was added
gene: NOTCH3 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: NOTCH3 was set to Unknown
Phenotypes for gene: NOTCH3 were set to CEREBRAL ARTERIOPATHY, AUTOSOMAL DOMINANT, WITH SUBCORTICAL INFARCTS AND LEUKOENCEPHALOPATHY
White matter disorders and cerebral calcification - narrow panel v0.11 MAT1A Ellen McDonagh gene: MAT1A was added
gene: MAT1A was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: MAT1A was set to Unknown
Publications for gene: MAT1A were set to 8770875
Phenotypes for gene: MAT1A were set to Calcifications in basal ganglia; Methionine adenosyltransferase deficiency, autosomal recessive
White matter disorders and cerebral calcification - narrow panel v0.11 HTRA1 Ellen McDonagh gene: HTRA1 was added
gene: HTRA1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: HTRA1 was set to Unknown
Phenotypes for gene: HTRA1 were set to CEREBRAL AUTOSOMAL RECESSIVE ARTERIOPATHY WITH SUBCORTICAL INFARCTS AND LEUKOENCEPHALOPATHY
White matter disorders and cerebral calcification - narrow panel v0.11 HSPD1 Ellen McDonagh gene: HSPD1 was added
gene: HSPD1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: HSPD1 was set to Unknown
Phenotypes for gene: HSPD1 were set to Leukodystrophy, hypomyelinating, 4, 612233; Spastic paraplegia 13, autosomal dominant, 605280
White matter disorders and cerebral calcification - narrow panel v0.11 SLC16A2 Ellen McDonagh gene: SLC16A2 was added
gene: SLC16A2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SLC16A2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SLC16A2 were set to Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_524
Phenotypes for gene: SLC16A2 were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy; Hypomyelinating Leukodystrophy & Pelizaeus-Merzbacher Disease; Monocarboxylate transporter 8 deficiency (MCT8); Allan-Herndon-Dudley syndrome
White matter disorders and cerebral calcification - narrow panel v0.11 RNF113A Ellen McDonagh gene: RNF113A was added
gene: RNF113A was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: RNF113A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: RNF113A were set to 25612912
Phenotypes for gene: RNF113A were set to ?Trichothiodystrophy 5, nonphotosensitive
White matter disorders and cerebral calcification - narrow panel v0.11 DCX Ellen McDonagh gene: DCX was added
gene: DCX was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: DCX was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: DCX were set to Lissencephaly, X-Linked, 1; Subcortical laminal heteropia, X-linked, 300067; Cerebral Malformation Disorders; Lissencephaly, X-linked, 300067; Classic Lissencephaly/Subcortical Band Heterotopia
White matter disorders and cerebral calcification - narrow panel v0.11 ARX Ellen McDonagh gene: ARX was added
gene: ARX was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ARX was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: ARX were set to 300215; Cerebral Malformation Disorders; Lissencephaly, X-linked 2
White matter disorders and cerebral calcification - narrow panel v0.11 AP1S2 Ellen McDonagh gene: AP1S2 was added
gene: AP1S2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: AP1S2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: AP1S2 were set to 17617514; 1842820
Phenotypes for gene: AP1S2 were set to Calcifications in basal ganglia
White matter disorders and cerebral calcification - narrow panel v0.11 PLP1 Ellen McDonagh gene: PLP1 was added
gene: PLP1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PLP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PLP1 were set to 25655951
Phenotypes for gene: PLP1 were set to Spastic paraplegia 2, X-linked 312920 Edit; Pelizaeus-Merzbacher disease 312080
White matter disorders and cerebral calcification - narrow panel v0.11 OCRL Ellen McDonagh gene: OCRL was added
gene: OCRL was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: OCRL was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: OCRL were set to Lowe syndrome, MIM#309000
White matter disorders and cerebral calcification - narrow panel v0.11 BCAP31 Ellen McDonagh gene: BCAP31 was added
gene: BCAP31 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: BCAP31 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: BCAP31 were set to Deafness, dystonia and cerebellar hypomyelination, 300475
White matter disorders and cerebral calcification - narrow panel v0.11 ATP7A Ellen McDonagh gene: ATP7A was added
gene: ATP7A was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ATP7A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ATP7A were set to 28495946; 28495940
Phenotypes for gene: ATP7A were set to Menkes disease, MIM#309400
White matter disorders and cerebral calcification - narrow panel v0.11 ABCD1 Ellen McDonagh gene: ABCD1 was added
gene: ABCD1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ABCD1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ABCD1 were set to 8040304; 11810273; 25655951
Phenotypes for gene: ABCD1 were set to Adrenomyeloneuropathy, adult, 300100; Adrenoleukodystrophy, X-linked; Adrenoleukodystrophy; Adrenoleukodystrophy, 300100; X-Linked Adrenoleukodystrophy
White matter disorders and cerebral calcification - narrow panel v0.11 ADGRG1 Ellen McDonagh gene: ADGRG1 was added
gene: ADGRG1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ADGRG1 was set to Unknown
Phenotypes for gene: ADGRG1 were set to Cerebral Malformation Disorders
White matter disorders and cerebral calcification - narrow panel v0.11 XPR1 Ellen McDonagh gene: XPR1 was added
gene: XPR1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: XPR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: XPR1 were set to 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
Phenotypes for gene: XPR1 were set to Basal ganglia calcification, idiopathic, 6, 616413; Basal ganglia calcification (Fahr syndrome)
White matter disorders and cerebral calcification - narrow panel v0.11 TMEM106B Ellen McDonagh gene: TMEM106B was added
gene: TMEM106B was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: TMEM106B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM106B were set to 29186371, 29444210
Phenotypes for gene: TMEM106B were set to Leukodystrophy, hypomyelinating 16, MIM#617964
White matter disorders and cerebral calcification - narrow panel v0.11 SCN2A Ellen McDonagh gene: SCN2A was added
gene: SCN2A was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: SCN2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN2A were set to PMID:24579881
Phenotypes for gene: SCN2A were set to Epileptic encephalopathy, early infantile, 11; Seizures, benign familial infantile, 3
White matter disorders and cerebral calcification - narrow panel v0.11 RAB11B Ellen McDonagh gene: RAB11B was added
gene: RAB11B was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: RAB11B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB11B were set to 29106825
Phenotypes for gene: RAB11B were set to Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter, MIM#617807
White matter disorders and cerebral calcification - narrow panel v0.11 IFIH1 Ellen McDonagh gene: IFIH1 was added
gene: IFIH1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: IFIH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: IFIH1 were set to Aicardi-Goutieres Syndrome; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Aicardi-Goutieres syndrome 7
White matter disorders and cerebral calcification - narrow panel v0.11 COL4A1 Ellen McDonagh gene: COL4A1 was added
gene: COL4A1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A1 were set to 22134833
Phenotypes for gene: COL4A1 were set to Variable phenotype - porencephaly, destructive cerebral lesions, eye anomalies, intracerebral calcification; Porencephaly 1
White matter disorders and cerebral calcification - narrow panel v0.11 TUBB4A Ellen McDonagh gene: TUBB4A was added
gene: TUBB4A was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TUBB4A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TUBB4A were set to 25655951
Phenotypes for gene: TUBB4A were set to Leukodystrophy, hypomyelinating, 6, 612438; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Leukodystrophy, hypomyelinating 6; Dystonia 4, torsion, autosomal dominant, 128101
White matter disorders and cerebral calcification - narrow panel v0.11 TUBA1A Ellen McDonagh gene: TUBA1A was added
gene: TUBA1A was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: TUBA1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TUBA1A were set to Lissencephaly 3; Lissencephaly, Dominant; Cerebral Malformation Disorders; Lissencephaly 3, 611603
White matter disorders and cerebral calcification - narrow panel v0.11 SOX10 Ellen McDonagh gene: SOX10 was added
gene: SOX10 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SOX10 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SOX10 were set to 25655951
Phenotypes for gene: SOX10 were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy; PERIPHERAL DEMYELINATING NEUROPATHY, CENTRAL DYSMYELINATING LEUKODYSTROPHY, WAARDENBURG SYNDROME, AND HIRSCHSPRUNG DISEASE; peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy
White matter disorders and cerebral calcification - narrow panel v0.11 SLC20A2 Ellen McDonagh gene: SLC20A2 was added
gene: SLC20A2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SLC20A2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SLC20A2 were set to 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
Phenotypes for gene: SLC20A2 were set to Fahr syndrome; Basal ganglia calcification, idiopathic, 1, 213600; Familial Idiopathic Basal Ganglia Calcification
White matter disorders and cerebral calcification - narrow panel v0.11 PDGFRB Ellen McDonagh gene: PDGFRB was added
gene: PDGFRB was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PDGFRB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PDGFRB were set to 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
Phenotypes for gene: PDGFRB were set to Fahr syndrome; Calcifications in basal ganglia; Basal ganglia calcification idiopathic 4, 615007
White matter disorders and cerebral calcification - narrow panel v0.11 PDGFB Ellen McDonagh gene: PDGFB was added
gene: PDGFB was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PDGFB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PDGFB were set to 26129893; 25211641; 27227165 - c.3G>C variant identified in 5 affected members of a family
Phenotypes for gene: PDGFB were set to Fahr syndrome; Basal ganglia calcification, idiopathic, 5, 615483
White matter disorders and cerebral calcification - narrow panel v0.11 PAFAH1B1 Ellen McDonagh gene: PAFAH1B1 was added
gene: PAFAH1B1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PAFAH1B1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PAFAH1B1 were set to Lissencephaly 1; Cerebral Malformation Disorders; Lissencephaly/Subcortical Band Heterotopia
White matter disorders and cerebral calcification - narrow panel v0.11 MEF2C Ellen McDonagh gene: MEF2C was added
gene: MEF2C was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: MEF2C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MEF2C were set to Mental Retardation, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations
White matter disorders and cerebral calcification - narrow panel v0.11 LMNB1 Ellen McDonagh gene: LMNB1 was added
gene: LMNB1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: LMNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LMNB1 were set to 21225301; 25655951; 21909802
Phenotypes for gene: LMNB1 were set to Leukodystrophy,adult-onset, autosomal dominant,169500; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Adult onset autosomal dominant leukodystrophy (ADLD)
Mode of pathogenicity for gene: LMNB1 was set to Other - please provide details in the comments
White matter disorders and cerebral calcification - narrow panel v0.11 GFAP Ellen McDonagh gene: GFAP was added
gene: GFAP was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: GFAP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GFAP were set to 25655951
Phenotypes for gene: GFAP were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy
Mode of pathogenicity for gene: GFAP was set to Other - please provide details in the comments
White matter disorders and cerebral calcification - narrow panel v0.11 CSF1R Ellen McDonagh gene: CSF1R was added
gene: CSF1R was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CSF1R was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CSF1R were set to Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_605
Phenotypes for gene: CSF1R were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 CIC Ellen McDonagh gene: CIC was added
gene: CIC was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CIC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CIC were set to 28288114; 24896178; 21076407
Phenotypes for gene: CIC were set to Mental retardation, autosomal dominant 45 617600
White matter disorders and cerebral calcification - narrow panel v0.11 TREX1 Ellen McDonagh gene: TREX1 was added
gene: TREX1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TREX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TREX1 were set to 25604658
Phenotypes for gene: TREX1 were set to Aicardi-Gouti res syndrome, isolated chilblains, lupus-like disease, retinal vasculopathy with cerebral leukodystrophy; Aicardi-Goutieres syndrome 1, dominant and recessive
White matter disorders and cerebral calcification - narrow panel v0.11 SPG7 Ellen McDonagh gene: SPG7 was added
gene: SPG7 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: SPG7 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SPG7 were set to 22571692, 17646629
Phenotypes for gene: SPG7 were set to Spastic paraplegia 7, autosomal recessive, MIM#607259
White matter disorders and cerebral calcification - narrow panel v0.11 MPZ Ellen McDonagh gene: MPZ was added
gene: MPZ was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: MPZ was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: MPZ were set to Neuropathy,congenital hypomyelinating,605253; Congenital Hypomyelination
White matter disorders and cerebral calcification - narrow panel v0.11 HEPACAM Ellen McDonagh gene: HEPACAM was added
gene: HEPACAM was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: HEPACAM was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: HEPACAM were set to 25655951
Phenotypes for gene: HEPACAM were set to Megalencephalic leukoencephalopathy with subcortical cysts (MLC); General Leukodystrophy & Mitochondrial Leukoencephalopathy; Megalencephalic leukoencephalopathy with subcortical cysts 2A; Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation
White matter disorders and cerebral calcification - narrow panel v0.11 GJA1 Ellen McDonagh gene: GJA1 was added
gene: GJA1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: GJA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: GJA1 were set to Oculodentodigital dysplasia, autosomal recessive 257850; Oculodentodigital dysplasia (AD) 164200
White matter disorders and cerebral calcification - narrow panel v0.11 ADAR Ellen McDonagh gene: ADAR was added
gene: ADAR was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ADAR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ADAR were set to 23001123; 25604658
Phenotypes for gene: ADAR were set to Aicardi-Goutieres syndrome; Aicardi-Gouti res, isolated spasticity, bilateral striatal necrosis; Aicardi-Goutieres syndrome 6
White matter disorders and cerebral calcification - narrow panel v0.11 ZFYVE26 Ellen McDonagh gene: ZFYVE26 was added
gene: ZFYVE26 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ZFYVE26 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZFYVE26 were set to Spastic paraplegia 15, autosomal recessive, MIM#270700
White matter disorders and cerebral calcification - narrow panel v0.11 XPC Ellen McDonagh gene: XPC was added
gene: XPC was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: XPC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPC were set to 27413738
Phenotypes for gene: XPC were set to Xeroderma pigmentosum, group C, 278720
White matter disorders and cerebral calcification - narrow panel v0.11 XPA Ellen McDonagh gene: XPA was added
gene: XPA was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: XPA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPA were set to 27603812; 27413738; 26302748; 26743599
Phenotypes for gene: XPA were set to Xeroderma pigmentosum, group A, 278700
White matter disorders and cerebral calcification - narrow panel v0.11 VPS11 Ellen McDonagh gene: VPS11 was added
gene: VPS11 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: VPS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS11 were set to 26307567, 27120463
Phenotypes for gene: VPS11 were set to Leukodystrophy, hypomyelinating, 12, MIM#616683
White matter disorders and cerebral calcification - narrow panel v0.11 USP18 Ellen McDonagh gene: USP18 was added
gene: USP18 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: USP18 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP18 were set to PMID: 27325888
Phenotypes for gene: USP18 were set to pseudo-TORCH syndrome
White matter disorders and cerebral calcification - narrow panel v0.11 UNC13D Ellen McDonagh gene: UNC13D was added
gene: UNC13D was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: UNC13D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UNC13D were set to 29312353
White matter disorders and cerebral calcification - narrow panel v0.11 TYROBP Ellen McDonagh gene: TYROBP was added
gene: TYROBP was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: TYROBP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TYROBP were set to Nasu-Hakola disease, MIM#221770
White matter disorders and cerebral calcification - narrow panel v0.11 TYMP Ellen McDonagh gene: TYMP was added
gene: TYMP was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TYMP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TYMP were set to 25655951
Phenotypes for gene: TYMP were set to Mitochondrial Leukoencephalopathy; Mitochondrial DNA depletion syndrome 1 (MNGIE type)
White matter disorders and cerebral calcification - narrow panel v0.11 TWNK Ellen McDonagh gene: TWNK was added
gene: TWNK was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TWNK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TWNK were set to 25655951
Phenotypes for gene: TWNK were set to Mitochondrial DNA depletion syndrome 7; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 TUFM Ellen McDonagh gene: TUFM was added
gene: TUFM was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: TUFM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUFM were set to 25735936 - summarises the findings of exome analysis in 109 patients. 16 out of 42 patients with a high suspicion of a mitochondrial disorder were reported as having a disease causing mutation found in the mitochondrial gene panel - of which TUFM was one of the genes with the biochemical diagnosis of combined OXPHOS enzyme deficiency.; 25655951; 17160893 (case report)
Phenotypes for gene: TUFM were set to Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 TREM2 Ellen McDonagh gene: TREM2 was added
gene: TREM2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TREM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TREM2 were set to 12080485; 15883308
Phenotypes for gene: TREM2 were set to Calcifications in basal ganglia; Nasu-Hakola disease; Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL)
White matter disorders and cerebral calcification - narrow panel v0.11 TACO1 Ellen McDonagh gene: TACO1 was added
gene: TACO1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: TACO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TACO1 were set to 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)
Phenotypes for gene: TACO1 were set to Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 SURF1 Ellen McDonagh gene: SURF1 was added
gene: SURF1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SURF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SURF1 were set to Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_560
Phenotypes for gene: SURF1 were set to Leigh syndrome, due to COX IV deficiency; Mitochondrial Leukoencephalopathy; Mitochondrial complex IV disorder
White matter disorders and cerebral calcification - narrow panel v0.11 SUMF1 Ellen McDonagh gene: SUMF1 was added
gene: SUMF1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SUMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUMF1 were set to Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_628
Phenotypes for gene: SUMF1 were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy; Multiple sulfatase deficiency
White matter disorders and cerebral calcification - narrow panel v0.11 SUCLA2 Ellen McDonagh gene: SUCLA2 was added
gene: SUCLA2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SUCLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUCLA2 were set to Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_575
Phenotypes for gene: SUCLA2 were set to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria); Mitochondrial Leukoencephalopathy; Mitochondrial DNA depletion syndrome 5
White matter disorders and cerebral calcification - narrow panel v0.11 SPG11 Ellen McDonagh gene: SPG11 was added
gene: SPG11 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: SPG11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPG11 were set to 14745065
Phenotypes for gene: SPG11 were set to Spastic paralplegia 11, autosomal recessive, MIM#604360
White matter disorders and cerebral calcification - narrow panel v0.11 SPART Ellen McDonagh gene: SPART was added
gene: SPART was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: SPART was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPART were set to 27112432, 18413476, 26003402, 12134148
Phenotypes for gene: SPART were set to Troyer syndrome, MIM#275900
White matter disorders and cerebral calcification - narrow panel v0.11 SNORD118 Ellen McDonagh gene: SNORD118 was added
gene: SNORD118 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: SNORD118 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNORD118 were set to 28177126; 27571260
Phenotypes for gene: SNORD118 were set to 614561
Mode of pathogenicity for gene: SNORD118 was set to Other - please provide details in the comments
White matter disorders and cerebral calcification - narrow panel v0.11 SLC25A4 Ellen McDonagh gene: SLC25A4 was added
gene: SLC25A4 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SLC25A4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A4 were set to Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_578; PMID: 27693233
Phenotypes for gene: SLC25A4 were set to Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 SLC25A1 Ellen McDonagh gene: SLC25A1 was added
gene: SLC25A1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: SLC25A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC25A1 were set to Global Cerebral Hypomyelination
White matter disorders and cerebral calcification - narrow panel v0.11 SLC17A5 Ellen McDonagh gene: SLC17A5 was added
gene: SLC17A5 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SLC17A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC17A5 were set to Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_634
Phenotypes for gene: SLC17A5 were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 SLC13A5 Ellen McDonagh gene: SLC13A5 was added
gene: SLC13A5 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: SLC13A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A5 were set to 27913086
Phenotypes for gene: SLC13A5 were set to Epileptic encephalopathy, early infantile 25, EIEE 25, MIM#615905
White matter disorders and cerebral calcification - narrow panel v0.11 SDHB Ellen McDonagh gene: SDHB was added
gene: SDHB was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SDHB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SDHB were set to 26642834 - multiple cases reported; 25655951; 26925370 - suggests incomplete penetrance; 22972948
Phenotypes for gene: SDHB were set to Succinate dehydrogenase-deficient leukoencephalopathy; complex II deficiency; Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 SDHAF1 Ellen McDonagh gene: SDHAF1 was added
gene: SDHAF1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SDHAF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SDHAF1 were set to 25655951; 22995659; 19465911
Phenotypes for gene: SDHAF1 were set to Mitochondrial complex II deficiency 252011
White matter disorders and cerebral calcification - narrow panel v0.11 SDHA Ellen McDonagh gene: SDHA was added
gene: SDHA was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: SDHA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SDHA were set to 22972948
Phenotypes for gene: SDHA were set to Mitochondrial respiratory chain complex II deficiency, MIM#252011
White matter disorders and cerebral calcification - narrow panel v0.11 SAMHD1 Ellen McDonagh gene: SAMHD1 was added
gene: SAMHD1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: SAMHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SAMHD1 were set to 25655951
Phenotypes for gene: SAMHD1 were set to Aicardi-Goutieres Syndrome; General Leukodystrophy & Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 RNASEH2C Ellen McDonagh gene: RNASEH2C was added
gene: RNASEH2C was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: RNASEH2C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2C were set to 27411419; 25655951
Phenotypes for gene: RNASEH2C were set to Aicardi-Goutieres Syndrome 3; General Leukodystrophy & Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 RNASEH2B Ellen McDonagh gene: RNASEH2B was added
gene: RNASEH2B was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: RNASEH2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2B were set to Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_586
Phenotypes for gene: RNASEH2B were set to Aicardi-Goutieres Syndrome; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Aicardi-Goutieres syndrome 2
White matter disorders and cerebral calcification - narrow panel v0.11 RNASEH2A Ellen McDonagh gene: RNASEH2A was added
gene: RNASEH2A was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: RNASEH2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2A were set to Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_585
Phenotypes for gene: RNASEH2A were set to Aicardi-Goutieres Syndrome; General Leukodystrophy & Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 RELN Ellen McDonagh gene: RELN was added
gene: RELN was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: RELN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RELN were set to Lissencephaly, Recessive; Lissencephaly 2; Lissencephaly 2 (Norman-Roberts type), 257320
White matter disorders and cerebral calcification - narrow panel v0.11 RARS Ellen McDonagh gene: RARS was added
gene: RARS was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: RARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RARS were set to 24777941; 27564080
Phenotypes for gene: RARS were set to Leukodystrophy, hypomyelinating, 9 616140
White matter disorders and cerebral calcification - narrow panel v0.11 PYCR2 Ellen McDonagh gene: PYCR2 was added
gene: PYCR2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PYCR2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PYCR2 were set to Leukodystrophy, hypomyelinating, 10 616420
White matter disorders and cerebral calcification - narrow panel v0.11 PRF1 Ellen McDonagh gene: PRF1 was added
gene: PRF1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: PRF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRF1 were set to 23443029
White matter disorders and cerebral calcification - narrow panel v0.11 PPT1 Ellen McDonagh gene: PPT1 was added
gene: PPT1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: PPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PPT1 were set to Ceroid lipofuscinosis, neuronal, 1, MIM#256730
White matter disorders and cerebral calcification - narrow panel v0.11 POLR3B Ellen McDonagh gene: POLR3B was added
gene: POLR3B was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: POLR3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3B were set to 25655951
Phenotypes for gene: POLR3B were set to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, 614381; Pol III-Related Leukodystrophy; General Leukodystrophy & Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 POLR1A Ellen McDonagh gene: POLR1A was added
gene: POLR1A was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: POLR1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR1A were set to 28051070
White matter disorders and cerebral calcification - narrow panel v0.11 POLH Ellen McDonagh gene: POLH was added
gene: POLH was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: POLH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLH were set to 23755135; 23651273; 24260050; 27004399; 25256075; 27664908; 24877075; 24130121; 25128761
Phenotypes for gene: POLH were set to Xeroderma pigmentosum, variant type, 278750
White matter disorders and cerebral calcification - narrow panel v0.11 PHGDH Ellen McDonagh gene: PHGDH was added
gene: PHGDH was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: PHGDH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PHGDH were set to Phosphoglycerate dehydrogenase deficiency, MIM#601815
White matter disorders and cerebral calcification - narrow panel v0.11 PEX6 Ellen McDonagh gene: PEX6 was added
gene: PEX6 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PEX6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX6 were set to 25655951
Phenotypes for gene: PEX6 were set to Peroxisome biogenesis disorder 4B 614863; Peroxisome biogenesis disorder 4A (Zellweger) 614862
White matter disorders and cerebral calcification - narrow panel v0.11 PEX3 Ellen McDonagh gene: PEX3 was added
gene: PEX3 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PEX3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX3 were set to 23245813; 10968777; 25655951
Phenotypes for gene: PEX3 were set to Peroxisome biogenesis disorder 10A (Zellweger) 614882
White matter disorders and cerebral calcification - narrow panel v0.11 PEX26 Ellen McDonagh gene: PEX26 was added
gene: PEX26 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PEX26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX26 were set to 25655951
Phenotypes for gene: PEX26 were set to Peroxisome-Associated Disorders & Zellweger Syndrome
White matter disorders and cerebral calcification - narrow panel v0.11 PEX16 Ellen McDonagh gene: PEX16 was added
gene: PEX16 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PEX16 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX16 were set to Peroxisome-Associated Disorders & Zellweger Syndrome; Peroxisome biogenesis disorder 8A, (Zellweger); Peroxisome biogenesis disorder 8B; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 9
White matter disorders and cerebral calcification - narrow panel v0.11 PEX14 Ellen McDonagh gene: PEX14 was added
gene: PEX14 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: PEX14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX14 were set to 15146459
Phenotypes for gene: PEX14 were set to Peroxisome-Associated Disorders & Zellweger Syndrome; PEROXISOME BIOGENESIS DISORDER 13A (ZELLWEGER)
White matter disorders and cerebral calcification - narrow panel v0.11 PEX13 Ellen McDonagh gene: PEX13 was added
gene: PEX13 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PEX13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX13 were set to 25655951
Phenotypes for gene: PEX13 were set to Peroxisome-Associated Disorders & Zellweger Syndrome; Peroxisome biogenesis disorder 11A (Zellweger); Peroxisome biogenesis disorder 11B
White matter disorders and cerebral calcification - narrow panel v0.11 PEX12 Ellen McDonagh gene: PEX12 was added
gene: PEX12 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PEX12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX12 were set to 25655951
Phenotypes for gene: PEX12 were set to Peroxisome-Associated Disorders & Zellweger Syndrome; Peroxisome biogenesis disorder 3A (Zellweger); General Leukodystrophy & Mitochondrial Leukoencephalopathy; Peroxisome biogenesis disorder 3B; Peroxisome biogenesis disorder 3A,B
White matter disorders and cerebral calcification - narrow panel v0.11 PEX10 Ellen McDonagh gene: PEX10 was added
gene: PEX10 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PEX10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX10 were set to 25655951
Phenotypes for gene: PEX10 were set to Peroxisome-Associated Disorders & Zellweger Syndrome; ZELLWEGER SYNDROME; PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 7
White matter disorders and cerebral calcification - narrow panel v0.11 PEX1 Ellen McDonagh gene: PEX1 was added
gene: PEX1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PEX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX1 were set to 25655951
Phenotypes for gene: PEX1 were set to Peroxisome-Associated Disorders & Zellweger Syndrome; Peroxisome biogenesis disorder 1A,B; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Peroxisome biogenesis disorder 1A (Zellweger)
White matter disorders and cerebral calcification - narrow panel v0.11 PCDH12 Ellen McDonagh gene: PCDH12 was added
gene: PCDH12 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: PCDH12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCDH12 were set to 27164683
Phenotypes for gene: PCDH12 were set to microcephaly; intellectual disability; perithalamic hyperechogenicity; hypothalamic abnormalities; periventricular hyperechogenicity; epilepsy; midbrain abnormalities
White matter disorders and cerebral calcification - narrow panel v0.11 OCLN Ellen McDonagh gene: OCLN was added
gene: OCLN was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: OCLN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OCLN were set to 24668585; 26689621; 23793442; 20727516
Phenotypes for gene: OCLN were set to Severe developmental delay with microcephaly; Band-like calcification with simplified gyration and polymicrogyria; Band-like calcification with simplified gyration and polymicrogyria, 251290
White matter disorders and cerebral calcification - narrow panel v0.11 NUBPL Ellen McDonagh gene: NUBPL was added
gene: NUBPL was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: NUBPL was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NUBPL were set to Mitochondrial complex I deficiency; Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 NDUFV1 Ellen McDonagh gene: NDUFV1 was added
gene: NDUFV1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: NDUFV1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFV1 were set to 26345448; 26758110; 27344648; 25655951
Phenotypes for gene: NDUFV1 were set to Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 NDUFS8 Ellen McDonagh gene: NDUFS8 was added
gene: NDUFS8 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: NDUFS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFS8 were set to 25655951
Phenotypes for gene: NDUFS8 were set to Mitochondrial complex I disorders; Leigh syndrome due to mitochondrial complex I deficiency; Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 NDUFS7 Ellen McDonagh gene: NDUFS7 was added
gene: NDUFS7 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: NDUFS7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFS7 were set to 25655951
Phenotypes for gene: NDUFS7 were set to Genetic leukoencephalopathies: mitochondrial disorders; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Leigh syndrome; Mitochondrial Leukoencephalopathy; Mitochondrial respiratory chain complex I deficiency
White matter disorders and cerebral calcification - narrow panel v0.11 NDUFS4 Ellen McDonagh gene: NDUFS4 was added
gene: NDUFS4 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: NDUFS4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFS4 were set to 25655951
Phenotypes for gene: NDUFS4 were set to Mitochondrial complex I deficiency; Mitochondrial complex I disorders; Mitochondrial Leukoencephalopathy; MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY
White matter disorders and cerebral calcification - narrow panel v0.11 NDUFS2 Ellen McDonagh gene: NDUFS2 was added
gene: NDUFS2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: NDUFS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFS2 were set to 20819849; 11220739; 25655951; 22036843; 23266820
Phenotypes for gene: NDUFS2 were set to Mitochondrial complex I disorders; Leigh syndrome associated with mitochondrial complex I deficiency; Mitochondrial Leukoencephalopathy; Leigh syndrome
White matter disorders and cerebral calcification - narrow panel v0.11 NDUFS1 Ellen McDonagh gene: NDUFS1 was added
gene: NDUFS1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: NDUFS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFS1 were set to 25655951
Phenotypes for gene: NDUFS1 were set to Mitochondrial complex I deficiency; Mitochondrial complex I disorders; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Mitochondrial Leukoencephalopathy; MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY
White matter disorders and cerebral calcification - narrow panel v0.11 NDUFAF1 Ellen McDonagh gene: NDUFAF1 was added
gene: NDUFAF1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: NDUFAF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFAF1 were set to 21931170; 16218961; 17557076; 25655951; 24963768
Phenotypes for gene: NDUFAF1 were set to Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 NDUFA2 Ellen McDonagh gene: NDUFA2 was added
gene: NDUFA2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: NDUFA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA2 were set to 28857146
Phenotypes for gene: NDUFA2 were set to Mitochondrial leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 NDE1 Ellen McDonagh gene: NDE1 was added
gene: NDE1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: NDE1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDE1 were set to Lissencephaly 4 (with microcephaly), 614019; Lissencephaly, Recessive; Cerebral Malformation Disorders
White matter disorders and cerebral calcification - narrow panel v0.11 NAXE Ellen McDonagh gene: NAXE was added
gene: NAXE was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: NAXE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAXE were set to 27616477, 27122014
Phenotypes for gene: NAXE were set to Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, MIM#617186
White matter disorders and cerebral calcification - narrow panel v0.11 MTFMT Ellen McDonagh gene: MTFMT was added
gene: MTFMT was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: MTFMT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTFMT were set to 21907147; 24461907; 27564080
Phenotypes for gene: MTFMT were set to Combined oxidative phosphorylation deficiency 15; 22499348; 614947; 23499752
White matter disorders and cerebral calcification - narrow panel v0.11 MRPS16 Ellen McDonagh gene: MRPS16 was added
gene: MRPS16 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: MRPS16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPS16 were set to 18539099; 15505824; 25655951
Phenotypes for gene: MRPS16 were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy; Combined oxidative phosphorylation deficiency 2; Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 MRE11 Ellen McDonagh gene: MRE11 was added
gene: MRE11 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: MRE11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRE11 were set to 21227757
Phenotypes for gene: MRE11 were set to Nijmegen breakage syndrome-like severe microcephaly
White matter disorders and cerebral calcification - narrow panel v0.11 MPLKIP Ellen McDonagh gene: MPLKIP was added
gene: MPLKIP was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: MPLKIP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MPLKIP were set to Non-photosensitive trichothiodystrophy 4
White matter disorders and cerebral calcification - narrow panel v0.11 MLC1 Ellen McDonagh gene: MLC1 was added
gene: MLC1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: MLC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MLC1 were set to 25655951
Phenotypes for gene: MLC1 were set to Megalencephalic leukoencephalopathy with subcortical cysts (MLC); General Leukodystrophy & Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 MFF Ellen McDonagh gene: MFF was added
gene: MFF was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: MFF was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MFF were set to Encephalopathy due to defective mitochondrial and peroxisomal fission 2 617086
White matter disorders and cerebral calcification - narrow panel v0.11 LYRM7 Ellen McDonagh gene: LYRM7 was added
gene: LYRM7 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: LYRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LYRM7 were set to 27151179; 27564080
Phenotypes for gene: LYRM7 were set to 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
White matter disorders and cerebral calcification - narrow panel v0.11 LAMB1 Ellen McDonagh gene: LAMB1 was added
gene: LAMB1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: LAMB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMB1 were set to 25925986; 17525174; 23472759
Phenotypes for gene: LAMB1 were set to Lissencephaly 5, 615191
White matter disorders and cerebral calcification - narrow panel v0.11 L2HGDH Ellen McDonagh gene: L2HGDH was added
gene: L2HGDH was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: L2HGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: L2HGDH were set to 25655951
Phenotypes for gene: L2HGDH were set to L2-Hydroxyglutaric aciduria
White matter disorders and cerebral calcification - narrow panel v0.11 JAM3 Ellen McDonagh Added phenotypes Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, 613730 for gene: JAM3
White matter disorders and cerebral calcification - narrow panel v0.11 JAM3 Ellen McDonagh gene: JAM3 was added
gene: JAM3 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: JAM3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: JAM3 were set to Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, 613730
White matter disorders and cerebral calcification - narrow panel v0.11 ISCA2 Ellen McDonagh gene: ISCA2 was added
gene: ISCA2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ISCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ISCA2 were set to 25558065; 22323289; 25539947; 27564080
White matter disorders and cerebral calcification - narrow panel v0.11 IBA57 Ellen McDonagh gene: IBA57 was added
gene: IBA57 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: IBA57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IBA57 were set to 28913435; 23462291; 25971455; 27785568; 28671726
Phenotypes for gene: IBA57 were set to Multiple mitochondrial dysfunctions syndrome 3, 615330
White matter disorders and cerebral calcification - narrow panel v0.11 HSD17B4 Ellen McDonagh gene: HSD17B4 was added
gene: HSD17B4 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: HSD17B4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSD17B4 were set to 25655951
Phenotypes for gene: HSD17B4 were set to Peroxisome-Associated Disorders & Zellweger Syndrome; General Leukodystrophy & Mitochondrial Leukoencephalopathy; D-bifunctional protein deficiency
White matter disorders and cerebral calcification - narrow panel v0.11 HMBS Ellen McDonagh gene: HMBS was added
gene: HMBS was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: HMBS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMBS were set to 27558376, 27271711
White matter disorders and cerebral calcification - narrow panel v0.11 HEXA Ellen McDonagh gene: HEXA was added
gene: HEXA was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: HEXA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEXA were set to MIM#272800
White matter disorders and cerebral calcification - narrow panel v0.11 GTF2H5 Ellen McDonagh gene: GTF2H5 was added
gene: GTF2H5 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: GTF2H5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GTF2H5 were set to Photosensitive trichothiodystrophy 3; Trichothiodystrophy 3, photosensitive
White matter disorders and cerebral calcification - narrow panel v0.11 GTF2E2 Ellen McDonagh gene: GTF2E2 was added
gene: GTF2E2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: GTF2E2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF2E2 were set to 26996949
Phenotypes for gene: GTF2E2 were set to Trichothiodystrophy 6, nonphotosensitive; 616943
White matter disorders and cerebral calcification - narrow panel v0.11 GJC2 Ellen McDonagh gene: GJC2 was added
gene: GJC2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: GJC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GJC2 were set to 25655951
Phenotypes for gene: GJC2 were set to Spastic paraplegia 44, autosomal recessive, 613206; Leukodystrophy, hypomyelinating, 2, 608804; Lymphedema, hereditary, IC, 613480
White matter disorders and cerebral calcification - narrow panel v0.11 GFM1 Ellen McDonagh gene: GFM1 was added
gene: GFM1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: GFM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GFM1 were set to 25655951
Phenotypes for gene: GFM1 were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy; Combined oxidative phosphorylation deficiency 1; Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 GBE1 Ellen McDonagh gene: GBE1 was added
gene: GBE1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: GBE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBE1 were set to 25655951
Phenotypes for gene: GBE1 were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy; Polyglucosan body disease, adult form; Polyglucosan Body Disease (PGBD)
White matter disorders and cerebral calcification - narrow panel v0.11 FUCA1 Ellen McDonagh gene: FUCA1 was added
gene: FUCA1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: FUCA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUCA1 were set to 25655951
Phenotypes for gene: FUCA1 were set to Fucosidosis; General Leukodystrophy & Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 FLVCR2 Ellen McDonagh gene: FLVCR2 was added
gene: FLVCR2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: FLVCR2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FLVCR2 were set to Proliferative vasculopathy and hydraencephaly-hydrocephaly syndrome, 225790
White matter disorders and cerebral calcification - narrow panel v0.11 FAM126A Ellen McDonagh gene: FAM126A was added
gene: FAM126A was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: FAM126A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM126A were set to 25655951
Phenotypes for gene: FAM126A were set to Hypomyelination and Congenital Cataract; Leukodystrophy, hypomyelinating, 5, 610532
White matter disorders and cerebral calcification - narrow panel v0.11 FA2H Ellen McDonagh gene: FA2H was added
gene: FA2H was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: FA2H was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FA2H were set to MIM#612319
White matter disorders and cerebral calcification - narrow panel v0.11 ETFDH Ellen McDonagh gene: ETFDH was added
gene: ETFDH was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ETFDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ETFDH were set to 25655951
Phenotypes for gene: ETFDH were set to Glutaric Acidemia IIC; Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 ERCC8 Ellen McDonagh gene: ERCC8 was added
gene: ERCC8 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ERCC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC8 were set to 26204423
Phenotypes for gene: ERCC8 were set to Cockayne syndrome phenotype and UV-sensitive syndrome; PMID: 26204423; Cockayne syndrome, type A
Mode of pathogenicity for gene: ERCC8 was set to Other - please provide details in the comments
White matter disorders and cerebral calcification - narrow panel v0.11 ERCC6 Ellen McDonagh gene: ERCC6 was added
gene: ERCC6 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ERCC6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC6 were set to 25655951
Phenotypes for gene: ERCC6 were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy; Cockayne syndrome; UV-sensitive syndrome
White matter disorders and cerebral calcification - narrow panel v0.11 ERCC5 Ellen McDonagh gene: ERCC5 was added
gene: ERCC5 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ERCC5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERCC5 were set to Xeroderma pigmentosum, group G, 278780; Xeroderma pigmentosum, group G/Cockayne syndrome, 278780
White matter disorders and cerebral calcification - narrow panel v0.11 ERCC4 Ellen McDonagh gene: ERCC4 was added
gene: ERCC4 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ERCC4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERCC4 were set to Xeroderma pigmentosum, type F/Cockayne syndrome, 278760; Xeroderma pigmentosum, group F, 278760
White matter disorders and cerebral calcification - narrow panel v0.11 ERCC3 Ellen McDonagh gene: ERCC3 was added
gene: ERCC3 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ERCC3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERCC3 were set to Xeroderma pigmentosum, group B, 610651; Trichothiodystrophy, 601675
White matter disorders and cerebral calcification - narrow panel v0.11 ERCC2 Ellen McDonagh gene: ERCC2 was added
gene: ERCC2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ERCC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERCC2 were set to Xeroderma pigmentosum, group D, 278730; Trichothiodystrophy, 601675
White matter disorders and cerebral calcification - narrow panel v0.11 ERCC1 Ellen McDonagh gene: ERCC1 was added
gene: ERCC1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ERCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC1 were set to 17273966 - ERCC1 deficiency in a patient with cerebro-oculo-facio-skeletal syndrome with a mild defect in nucleotide excision repair and severe developmental failure; 23623389 - homozygous missense variant reported in a patient with Cockayne syndrome
Phenotypes for gene: ERCC1 were set to Xeroderma Pigmentosum
White matter disorders and cerebral calcification - narrow panel v0.11 EIF2B5 Ellen McDonagh gene: EIF2B5 was added
gene: EIF2B5 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: EIF2B5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF2B5 were set to 12325082; 25655951; 11704758
Phenotypes for gene: EIF2B5 were set to Leukoencephalopathy with vanishing white matter, 603896; Ovarioleukodystrophy, 603896; General Leukodystrophy & Mitochondrial Leukoencephalopathy; eIF2B related disorder (Vanishing WM Disease or CACH)
White matter disorders and cerebral calcification - narrow panel v0.11 EIF2B4 Ellen McDonagh gene: EIF2B4 was added
gene: EIF2B4 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: EIF2B4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF2B4 were set to 11835386; 25089094; 25655951; 12707859; 26043506
Phenotypes for gene: EIF2B4 were set to Ovarioleukodystrophy, 603896; Leukoencephaly with vanishing white matter, 603896
White matter disorders and cerebral calcification - narrow panel v0.11 EIF2B3 Ellen McDonagh gene: EIF2B3 was added
gene: EIF2B3 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: EIF2B3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF2B3 were set to 11835386; 25655951; 19158808
Phenotypes for gene: EIF2B3 were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy; Leukoencephalopathy with vanishing white matter 603896; eIF2B related disorder (Vanishing WM Disease or CACH)
White matter disorders and cerebral calcification - narrow panel v0.11 EIF2B2 Ellen McDonagh gene: EIF2B2 was added
gene: EIF2B2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: EIF2B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF2B2 were set to 25655951
Phenotypes for gene: EIF2B2 were set to 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
White matter disorders and cerebral calcification - narrow panel v0.11 EIF2B1 Ellen McDonagh gene: EIF2B1 was added
gene: EIF2B1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: EIF2B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF2B1 were set to 16807905; 25655951; 15776425
Phenotypes for gene: EIF2B1 were set to 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)
White matter disorders and cerebral calcification - narrow panel v0.11 EARS2 Ellen McDonagh gene: EARS2 was added
gene: EARS2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: EARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EARS2 were set to 25655951
Phenotypes for gene: EARS2 were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy; Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL); Combined oxidative phosphorylation deficiency 12
White matter disorders and cerebral calcification - narrow panel v0.11 DGUOK Ellen McDonagh gene: DGUOK was added
gene: DGUOK was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: DGUOK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DGUOK were set to 25655951
Phenotypes for gene: DGUOK were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy; Mitochondrial Leukoencephalopathy; Mitochondrial DNA depletion syndrome 3
White matter disorders and cerebral calcification - narrow panel v0.11 DDB2 Ellen McDonagh gene: DDB2 was added
gene: DDB2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: DDB2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DDB2 were set to Xeroderma pigmentosum, group E, DDB-negative subtype, 278740
White matter disorders and cerebral calcification - narrow panel v0.11 DARS2 Ellen McDonagh gene: DARS2 was added
gene: DARS2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: DARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DARS2 were set to 25655951
Phenotypes for gene: DARS2 were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy; Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL)
White matter disorders and cerebral calcification - narrow panel v0.11 D2HGDH Ellen McDonagh gene: D2HGDH was added
gene: D2HGDH was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: D2HGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: D2HGDH were set to 25655951
Phenotypes for gene: D2HGDH were set to L2-Hydroxyglutaric aciduria
White matter disorders and cerebral calcification - narrow panel v0.11 CYP7B1 Ellen McDonagh gene: CYP7B1 was added
gene: CYP7B1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: CYP7B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP7B1 were set to MIM#270800
White matter disorders and cerebral calcification - narrow panel v0.11 CYP2U1 Ellen McDonagh gene: CYP2U1 was added
gene: CYP2U1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CYP2U1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYP2U1 were set to Spastic paraplegia 56, autosomal recessive
White matter disorders and cerebral calcification - narrow panel v0.11 CYP27A1 Ellen McDonagh gene: CYP27A1 was added
gene: CYP27A1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CYP27A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP27A1 were set to 25655951
Phenotypes for gene: CYP27A1 were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy; Cerebrotendinous xanthomatosis
White matter disorders and cerebral calcification - narrow panel v0.11 CTC1 Ellen McDonagh gene: CTC1 was added
gene: CTC1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CTC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTC1 were set to 22387016; 22267198
Phenotypes for gene: CTC1 were set to Coats Plus syndrome; Cerebroretinal microangiopathy with calcifications and cysts, 612199
White matter disorders and cerebral calcification - narrow panel v0.11 COX15 Ellen McDonagh gene: COX15 was added
gene: COX15 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: COX15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX15 were set to 25655951
Phenotypes for gene: COX15 were set to Mitochondrial complex IV disorders; Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 COX10 Ellen McDonagh gene: COX10 was added
gene: COX10 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: COX10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX10 were set to 24100867; 25655951; 12928484
Phenotypes for gene: COX10 were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy; Mitochondrial Leukoencephalopathy; Mitochondrial complex IV disorder
White matter disorders and cerebral calcification - narrow panel v0.11 COQ9 Ellen McDonagh gene: COQ9 was added
gene: COQ9 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: COQ9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ9 were set to 25655951; 19375058
Phenotypes for gene: COQ9 were set to Coenzyme Q10 deficiency, primary, 5; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 COQ8A Ellen McDonagh gene: COQ8A was added
gene: COQ8A was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: COQ8A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ8A were set to 25655951
Phenotypes for gene: COQ8A were set to Coenzyme Q10 deficiency, primary, 4
White matter disorders and cerebral calcification - narrow panel v0.11 COQ2 Ellen McDonagh gene: COQ2 was added
gene: COQ2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: COQ2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ2 were set to 25655951
Phenotypes for gene: COQ2 were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy; Mitochondrial Leukoencephalopathy; Coenzyme Q10 deficiency, primary, 1
White matter disorders and cerebral calcification - narrow panel v0.11 CNTNAP1 Ellen McDonagh gene: CNTNAP1 was added
gene: CNTNAP1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: CNTNAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNTNAP1 were set to 29882456
White matter disorders and cerebral calcification - narrow panel v0.11 CLCN2 Ellen McDonagh gene: CLCN2 was added
gene: CLCN2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: CLCN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLCN2 were set to 25655951
Phenotypes for gene: CLCN2 were set to Leukoencephalopathy with ataxia; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Chloride Ion Channel 2(ClC-2) related leukoencephalopathy with intramyelinic oedema
White matter disorders and cerebral calcification - narrow panel v0.11 BOLA3 Ellen McDonagh gene: BOLA3 was added
gene: BOLA3 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: BOLA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BOLA3 were set to 29654549, 29501406, 24334290, 21944046
White matter disorders and cerebral calcification - narrow panel v0.11 BCS1L Ellen McDonagh gene: BCS1L was added
gene: BCS1L was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: BCS1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BCS1L were set to 25655951
Phenotypes for gene: BCS1L were set to Mitochondrial complex III disorders; Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 ATPAF2 Ellen McDonagh gene: ATPAF2 was added
gene: ATPAF2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: ATPAF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATPAF2 were set to 25655951; 14757859; 21815885 (no variants identified)
Phenotypes for gene: ATPAF2 were set to Mitochondrial complex V disorders; General Leukodystrophy & Mitochondrial Leukoencephalopathy; Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 ASPA Ellen McDonagh gene: ASPA was added
gene: ASPA was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ASPA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASPA were set to 25655951
Phenotypes for gene: ASPA were set to General Leukodystrophy & Mitochondrial Leukoencephalopathy; 25655951
White matter disorders and cerebral calcification - narrow panel v0.11 ALDH3A2 Ellen McDonagh gene: ALDH3A2 was added
gene: ALDH3A2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ALDH3A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALDH3A2 were set to 25655951
Phenotypes for gene: ALDH3A2 were set to Sjogren Larsson syndrome; General Leukodystrophy & Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 ACP5 Ellen McDonagh gene: ACP5 was added
gene: ACP5 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ACP5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACP5 were set to 21217752; 21217755; 26951490
Phenotypes for gene: ACP5 were set to Spondyloenchondrodysplasia, short stature, SLE, intracranial calcification, spasticity, chilblains, autoimmune haemolytic anaemia; Spondyloenchondrodysplasia with immune dysregulation
White matter disorders and cerebral calcification - narrow panel v0.11 ACOX1 Ellen McDonagh gene: ACOX1 was added
gene: ACOX1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: ACOX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACOX1 were set to Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_648; 17458872; 25655951; 11815777
Phenotypes for gene: ACOX1 were set to Peroxisomal acyl-CoA oxidase deficiency 264470; General Leukodystrophy & Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 ACBD5 Ellen McDonagh gene: ACBD5 was added
gene: ACBD5 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Red
Mode of inheritance for gene: ACBD5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACBD5 were set to 27799409, 27899449, 23105016
White matter disorders and cerebral calcification - narrow panel v0.11 AARS2 Ellen McDonagh gene: AARS2 was added
gene: AARS2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: AARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AARS2 were set to 24808023; 27251004; 25655951; 25705216
Phenotypes for gene: AARS2 were set to Leukoencephalopathy with ovarian failure; General Leukodystrophy & Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v0.11 PEX5 Ellen McDonagh gene: PEX5 was added
gene: PEX5 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PEX5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX5 were set to 27290639; 26220973
Phenotypes for gene: PEX5 were set to Peroxisome biogenesis disorder 2A (Zellweger)
White matter disorders and cerebral calcification - narrow panel v0.11 RRM2B Ellen McDonagh gene: RRM2B was added
gene: RRM2B was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: RRM2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RRM2B were set to 25655951
Phenotypes for gene: RRM2B were set to Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy)
White matter disorders and cerebral calcification - narrow panel v0.11 PEX2 Ellen McDonagh gene: PEX2 was added
gene: PEX2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Green
Mode of inheritance for gene: PEX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX2 were set to 25655951
Phenotypes for gene: PEX2 were set to Peroxisome biogenesis disorder 5A (Zellweger)