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| Likely inborn error of metabolism - targeted testing not possible v4.132 | ALAS2 | Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Erythropoietic protoporphyria, mild variant; X-linked sideroblastic anaemia (XLSA) (Porphyrias with acute painful photosensitivity); X-linked dominant protoporphyria (Porphyrias with acute painful photosensitivity) to Anemia, sideroblastic, 1, OMIM:300751; Protoporphyria, erythropoietic, X-linked, OMIM:300752 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v4.125 | GSTZ1 |
Achchuthan Shanmugasundram Added comment: Comment on list classification: As reported in PMID:27876694 and reviewed by Saikat Santra, there are three boys and three girls with maleylacetoacetate isomerase deficiency (MAAID), identified by newborn screening with mildly elevated succinylacetone (SA) by mass spectrometry on dried blood spot. Four of them were identified with homozygous GSTZ1 variants, one with compound heterozygous variants and one with heterozygous variant. Hence, there is sufficient evidence available for the association of biallelic GSTZ1 variants with MAAID and this gene can be promoted to green rating in the next GMS review. |
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| Likely inborn error of metabolism - targeted testing not possible v4.117 | VPS33A |
Sarah Leigh gene: VPS33A was added gene: VPS33A was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Other Q4_23_promote_green tags were added to gene: VPS33A. Mode of inheritance for gene: VPS33A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS33A were set to 28013294; 27547915; 31070736 Phenotypes for gene: VPS33A were set to Mucopolysaccharidosis-plus syndrome OMIM:617303; mucopolysaccharidosis-like syndrome with congenital heart defects and hematopoietic disorders MONDO:0015012 Review for gene: VPS33A was set to GREEN Added comment: This gene has been copied from Lysosomal storage disorder panel: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least one variant was reported in two Turkish sisters (PMID 27547915) and in the Yakut population in the Russian Federation (PMID 28013294), where haplotype evidence suggested a founder effect in the Russian population. Supportive functional studies were also presented (PMID 31070736). Sarah Leigh (Genomics England Curator), 17 Mar 2021 Single variant (R498W) reported in the Turkish and Yakut population. Functional studies support association of this gene to lysosomal dysfunction. Sources: Expert list Zornitza Stark (Australian Genomics), 22 Jul 2020 Sources: Other |
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| Likely inborn error of metabolism - targeted testing not possible v4.115 | VPS16 |
Sarah Leigh Added comment: Comment on mode of inheritance: Biallelic variants are associated with a phenotype resembling a lysosomal storage disease. There are sufficient families (3) and functional data showing defects in the endolysosomal trafficking system to support inclusion for this allelic requirement. Monoallelic variants are linked to dystonia but only one study performed further analyses that suggested lysosomal dysfunction. Therefore while possible, it is unclear whether the 'Lysosomal storage disorder' panel would be applied in these cases. VPS16 will be flagged for GMS review with regards to the most appropriate MOI on this panel (biallelic or both bilalleic/monoallelic) Arina Puzriakova (Genomics England Curator), 14 Jun 2021 |
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| Likely inborn error of metabolism - targeted testing not possible v4.110 | CTSF | Sarah Leigh edited their review of gene: CTSF: Added comment: Emma Ashton (Great Ormond Street Hospital) ([email protected]); Variants in this GENE are reported as part of current diagnostic practice.; Changed rating: GREEN; Set current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v4.108 | CLCN6 | Sarah Leigh edited their review of gene: CLCN6: Added comment: PMID 33217309 reports gain of function associated with CLCN6 variants.; Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v4.106 | LMF1 | Sarah Leigh changed review comment from: PMID 17994020 and 19820022, both report homozygous terminating variants in severe hypertriglyceridemia, together with functional studies that showed significant reduction of LPL activity. PMID 30885219: heterozygous LMF1 c.1024C > T (p.Arg342*; rs776584760) in a patient with Hypertriglyceridemia and acute pancreatitis (HTG-AP). PMID: 30420299 reports at least 2 likely pathogenic (terminating variants) heterozygous LMF1 variants from 13 variants in severe hypertriglyceridemia patients. PMID: 29910226 reports a compound heterozygous variants (c.257C>T, p.P86L & c.1184C>T,p.T395I) which segrates with hypertriglyceridemia in the family. However PMID: 22239554 reports that a number of missense variants don't have an effect.; to: PMID 17994020 and 19820022, both report homozygous terminating variants in severe hypertriglyceridemia, together with functional studies that showed significant reduction of LPL activity. PMID 30885219: heterozygous LMF1 c.1024C > T (p.Arg342*; rs776584760) in a patient with Hypertriglyceridemia and acute pancreatitis (HTG-AP). PMID: 30420299 reports at least 2 likely pathogenic (terminating variants) heterozygous LMF1 variants from 13 variants in severe hypertriglyceridemia patients. PMID: 29910226 reports a compound heterozygous variants (c.257C>T, p.P86L & c.1184C>T,p.T395I) which segregates with hypertriglyceridemia in the family. However PMID: 22239554 reports that a number of missense variants don't have an effect. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v4.106 | LMF1 | Sarah Leigh commented on gene: LMF1: PMID 17994020 and 19820022, both report homozygous terminating variants in severe hypertriglyceridemia, together with functional studies that showed significant reduction of LPL activity. PMID 30885219: heterozygous LMF1 c.1024C > T (p.Arg342*; rs776584760) in a patient with Hypertriglyceridemia and acute pancreatitis (HTG-AP). PMID: 30420299 reports at least 2 likely pathogenic (terminating variants) heterozygous LMF1 variants from 13 variants in severe hypertriglyceridemia patients. PMID: 29910226 reports a compound heterozygous variants (c.257C>T, p.P86L & c.1184C>T,p.T395I) which segrates with hypertriglyceridemia in the family. However PMID: 22239554 reports that a number of missense variants don't have an effect. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v4.106 | LMF1 |
Sarah Leigh gene: LMF1 was added gene: LMF1 was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Expert list Q4_23_promote_green tags were added to gene: LMF1. Mode of inheritance for gene: LMF1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LMF1 were set to 17994020; 19820022; 30885219; 30420299; 29910226; 22239554 Phenotypes for gene: LMF1 were set to Lipase deficiency, combined OMIM:246650; lipase deficiency, combined MONDO:0009527 Review for gene: LMF1 was set to GREEN gene: LMF1 was marked as current diagnostic Added comment: LMF1 Familial chylomicronaemia syndrome (FCS) panel. Maggie Williams (North Bristol NHS Trust) [email protected]: Variants in this GENE are reported as part of current diagnostic practice Sources: Expert list |
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| Likely inborn error of metabolism - targeted testing not possible v4.104 | GPIHBP1 |
Sarah Leigh gene: GPIHBP1 was added gene: GPIHBP1 was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Expert list Q4_23_promote_green tags were added to gene: GPIHBP1. Mode of inheritance for gene: GPIHBP1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GPIHBP1 were set to Hyperlipoproteinemia, type 1D OMIM:615947; hyperlipoproteinemia, type 1D MONDO:0014412 Review for gene: GPIHBP1 was set to GREEN Added comment: GPIHBP1 copied from Familial chylomicronaemia syndrome (FCS) panel. Maggie Williams (North Bristol NHS Trust)([email protected]): Variants in this GENE are reported as part of current diagnostic practice Sources: Expert list |
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| Likely inborn error of metabolism - targeted testing not possible v4.94 | NUS1 |
Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As reviewed by Dmitrijs Rots, there are more than three unrelated cases and functional evidence available in support of the association of monoallelic NUS1 variants with intellectual disability and epilepsy. This autosomal dominant disorder has been recorded in both OMIM (MIM #617831) and Gene2Phenotype (with 'strong' rating in the DD panel). However, there is only one family and supporting functional evidence available for the association of biallelic variants with congenital disorder of glycosylation. This phenotype has already been recorded in OMIM (MIM #617082), but not in Gene2Phenotype. Hence, the MOI should be updated from 'BIALLELIC, autosomal or pseudoautosomal' to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'. |
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| Likely inborn error of metabolism - targeted testing not possible v4.90 | ATP5E | Sarah Leigh edited their review of gene: ATP5E: Added comment: PMID: 34954817 reports two further cases of OMIM: 614053 who are both homozygous for ATP5E (new gene name: ATP5F1E) variant c.35A>G, p.Tyr12Cys (rs387906929), previously reported in PubMed: 20566710. Personal communication with the lead author of PMID: 34954817, confirmed that none of these cases were related to one another and so represent independent occurrences of this variant.; Changed rating: GREEN; Changed publications to: 27604308, 34954817, 20566710 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v4.88 | LDHD | Sarah Leigh edited their review of gene: LDHD: Added comment: LDHD variants have been associated with D-lactic aciduria with susceptibility to gout (OMIM:245450), but not with a phenotype in Gen2Phen. At least seven LDHD variants have been reported in seven unrelated cases (PMID: 30931947;31638601;34258137;37021930).; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v4.77 | LDHD |
Hannah Knight gene: LDHD was added gene: LDHD was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Literature Mode of inheritance for gene: LDHD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LDHD were set to 30931947; 31638601 Phenotypes for gene: LDHD were set to D-lactic aciduria with susceptibility to gout Review for gene: LDHD was set to AMBER Added comment: PMID: 30931947 (2019) reported two unrelated patients with homozygous missense variants in LDHD (p.Thr463Met and p.Trp374Cys) PMID: 31638601 (2019) reported a 4-generation consanguineous Bedouin-Israeli family with autosomal recessive hyperuricemia. A homozygous missense variant in LDHD was identified (p.R370W) Sources: Literature |
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| Likely inborn error of metabolism - targeted testing not possible v4.77 | ACACA |
Hannah Knight gene: ACACA was added gene: ACACA was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Literature Mode of inheritance for gene: ACACA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACACA were set to 34552920 Phenotypes for gene: ACACA were set to Acetyl-CoA carboxylase deficiency Review for gene: ACACA was set to AMBER Added comment: PMID: 34552920 (2021) reported a baby who presented in her first two years of life with global developmental delay, microcephaly, hypotonia, and dysmorphic facial features. Two VUS's in ACACA were identified, and a decreased level of ACC1 and ACC1 enzyme activity was detected in patient-derived lymphocytes. In vitro studies revealed a disruption of lipid homeostasis in patient-derived lymphocytes, further inducing the deficit of cell motility capacity and that the deficiency could be partly attenuated by palmitate. Sources: Literature |
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| Likely inborn error of metabolism - targeted testing not possible v4.77 | PIGM |
Sarah Leigh edited their review of gene: PIGM: Added comment: A single PIGM variant (NM_145167.2(PIGM):c.-270C>G)(rs587776528) has been associated with Glycosylphosphatidylinositol deficiency, (OMIM:610293) and as limited Gen2Phen gene for the same condition. To date, this variant has only been reported in people of Arab or Turkish descent. Microsatellite- and SNP-based haplotypes encompassing PIGM reported in PMID:19168132, suggested that a founder effect in the two families (one Arab and one Turkish) was unlikely. However, subsequent occurrences of the variant in two additional unrelated Arab families (PMID: 31445883) might suggest that this variant is confined within the Middle Eastern populations. Functional studies have shown that this variant reduces transcription of PIGM and blocks mannosylation of glycosylphosphatidylinositol anchor (PMID: 16767100).; Changed rating: GREEN |
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| Likely inborn error of metabolism - targeted testing not possible v4.64 | PTCD3 | Sarah Leigh edited their review of gene: PTCD3: Added comment: PTCD3 variants are associated with ?Combined oxidative phosphorylation deficiency 51 (OMIM:619057), but not associated with phenotype in Gen2Phen. At least six variants have been reported in three unrelated cases, with OMIM:619057 (PMID: 30607703; 36450274). Functional studies also support the involvement of PTCD3 variants in this condition (PMID: 30607703; 36450274).; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v4.59 | MRM2 | Sarah Leigh edited their review of gene: MRM2: Added comment: MRM2 variants have been associated with ?Mitochondrial DNA depletion syndrome 17 (OMIM:618567), but not associated with phenotype in Gen2Phen. To date three biallelic MRM2 variants have been reported three unrelated cases (PMID: 28973171;36002240), supportive yeast functional studies have also been presented (PMID: 36002240).; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v4.57 | SEC23B |
Arina Puzriakova Added comment: Comment on mode of inheritance: There is limited evidence linking this gene with Cowden syndrome (monoallelic variants). Only one family has been reported to date (PMID:26522472). This gene:disease association is provisional in OMIM, 'limited' disease confidence category in G2P and is not listed in ClinGen (whereas CDAII is). Biallelic phenotype remains relevant to this panel (PMID: 35163229). On this basis, the MOI should be updated from 'Both mono- and biallelic' to 'Biallelic' only at the next GMS panel update. |
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| Likely inborn error of metabolism - targeted testing not possible v4.44 | LETM1 |
Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as moderate Gen2Phen gene. PMID: 36055214 reports 12 LETM1 variants in 11 unrelated cases of Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction (OMIM: 620089), together with supportive functional studies.; to: LETM1 variants have been associated with Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089 and as moderate Gen2Phen gene for LETM1-related neurodevelopmental disorder. PMID: 36055214 reports 10 LETM1 variants in 18 patients from 11 unrelated families with childhood-onset neurodegeneration with multisystem involvement, many of whom were gathered using the GeneMatcher Program. The most common clinical features of this cohort, where an assessment could be made, were: mitochondrial respiratory complex deficiencies 11/11 (100%), global developmental delay / intellectual disability 17/18 (94%), bilateral sensorineural hearing loss 11/14 (78%) , impaired vision 10/10 (100%), cerebellar ataxia 7/9 (78%), seizures 10/15 (67%), hypotonia 11/18 (61%) (PMID: 36055214, figure 1c). |
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| Likely inborn error of metabolism - targeted testing not possible v4.42 | SLC22A5 | Sarah Leigh Phenotypes for gene: SLC22A5 were changed from Propionicacidemia; Carnitine transporter deficiency (Disorders of carnitine transport and the carnitine cycle) to Carnitine deficiency, systemic primary, OMIM:212140; systemic primary carnitine deficiency disease, MONDO:0008919 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v4.37 | ETFA | Sarah Leigh edited their review of gene: ETFA: Added comment: Associated with phenotype in OMIM and as a definitive Developmental Disorder Gene / G2P. At least five ETFA variants have been reported, two in homozygous and compound heterozygous cases and three as compound heterozygotes (at least eight unrelated cases).; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v4.4 | ATP5O | Arina Puzriakova Added comment: Comment on list classification: There are now sufficient unrelated cases reported (3) to promote this gene to Green at the next GMS panel update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v4.2 | SPG7 | Sarah Leigh edited their review of gene: SPG7: Added comment: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form) autosomal or pseudoautosomal.; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v3.13 | SLC31A1 |
Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency. This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM. |
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| Likely inborn error of metabolism - targeted testing not possible v3.13 | SLC31A1 |
Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency. This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM. |
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| Likely inborn error of metabolism - targeted testing not possible v3.13 | SLC31A1 |
Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency. This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM. |
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| Likely inborn error of metabolism - targeted testing not possible v3.12 | SLC31A1 |
Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency. This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM. |
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| Likely inborn error of metabolism - targeted testing not possible v3.12 | SLC31A1 |
Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency. This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM. |
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| Likely inborn error of metabolism - targeted testing not possible v3.12 | SLC31A1 |
Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency. This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM. |
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| Likely inborn error of metabolism - targeted testing not possible v3.11 | SLC31A1 |
Achchuthan Shanmugasundram gene: SLC31A1 was added gene: SLC31A1 was added to Inborn errors of metabolism. Sources: Literature Mode of inheritance for gene: SLC31A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC31A1 were set to 35913762; 36562171 Phenotypes for gene: SLC31A1 were set to Neurodevelopmental disorder, MONDO:0700092 Review for gene: SLC31A1 was set to AMBER Added comment: PMID:35913762 reported an identical twin male infants identified with homozygous novel missense variant p.Arg95His in CTR1. The twins had hypotonia, global developmental delay, seizures, and rapid brain atrophy, consistent with profound central nervous system copper deficiency. In addition, the CSF copper levels were lower and functional studies including structural modelling of the variant showed impaired copper transport. Treatment with copper Histidinate in the patients' cultured cells and in the patients normalized CCO activity and enhanced mitochondrial respiration in vitro, and was associated with modest clinical improvements. PMID:36562171 reported a newborn infant of consanguineous parents with a homozygous pathogenic variant p.Leu79Pro in CTR1. This infant was born with pulmonary hypoplasia. At two weeks of age, multifocal brain hemorrhages were diagnosed and the infant developed seizures. Laboratory investigations revealed very low serum concentrations of copper and ceruloplasmin. The infant died at one month of age. Sources: Literature |
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| Likely inborn error of metabolism - targeted testing not possible v3.10 | CRLS1 | Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are three unrelated cases and supporting functional evidence to link this gene with a mitochondrial metabolic disorder. This gene has already been associated with this phenotype in OMIM (MIM #620167). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v3.10 | CRLS1 | Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are three unrelated cases and supporting functional evidence to link this gene with a mitochondrial metabolic disorder. This gene has already been associated with this phenotype in OMIM (MIM #620167). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v3.9 | CRLS1 | Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are three unrelated cases and supporting functional evidence to link this gene with a mitochondrial metabolic disorder. This gene has already been associated with this phenotype in OMIM (MIM #620167). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v3.9 | CRLS1 | Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are three unrelated cases and supporting functional evidence to link this gene with a mitochondrial metabolic disorder. This gene has already been associated with this phenotype in OMIM (MIM #620167). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v3.2 | SLC26A6 |
Arina Puzriakova gene: SLC26A6 was added gene: SLC26A6 was added to Inborn errors of metabolism. Sources: Literature watchlist tags were added to gene: SLC26A6. Mode of inheritance for gene: SLC26A6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SLC26A6 were set to 35115415 Phenotypes for gene: SLC26A6 were set to Enteric hyperoxaluria and nephrolithiasis Added comment: Cornière et al. 2022 (PMID: 35115415) identified a single family with a heterozygous missense VUS (c.1519C>T/p.R507W) in the SLC26A6 gene. However, the variant was found in 5 out of 280 674 alleles reported in gnomAD (Europeans and South Asians). In vitro studies showed that the variant affects both SLC26A6 transport activity and membrane surface expression, in turn reducing Cl− dependant oxalate transport. Cotransfection studies indicated a dominant-negative effect on WT. Slc26a6 null mice similarly displayed hyperoxalemia and hyperoxaluria which were caused by defective intestinal back-secretion of dietary oxalate (PMID: 21170874; 32660969) SLC26A6 is currently not associated with any human phenotype in OMIM or G2P. Sources: Literature |
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| Likely inborn error of metabolism - targeted testing not possible v2.328 | ARSK |
Arina Puzriakova gene: ARSK was added gene: ARSK was added to Inborn errors of metabolism. Sources: Literature Mode of inheritance for gene: ARSK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARSK were set to 34916232 Phenotypes for gene: ARSK were set to Mucopolysaccharidoses with short stature, coarse facial features and dysostosis multiplex Review for gene: ARSK was set to AMBER Added comment: Verheyen et al. 2022 (PMID: 34916232) reported four affected individuals of two unrelated consanguineous families with homozygous variants c.250C>T, p.(Arg84Cys) and c.560T>A, p.(Leu187Ter) in ARSK, respectively. Patients were affected with skeletal dysplasia, resembling spondyloepiphysial dysplasia. Reverse phenotyping in two individuals from one family revealed additional cardiac and ophthalmological abnormalities. Sources: Literature |
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| Likely inborn error of metabolism - targeted testing not possible v2.310 | NFS1 | Arina Puzriakova Added comment: Comment on list classification: There is now sufficient evidence to promote this gene to Green at the next GMS review - associated with relevant phenotype in OMIM (MIM#619386) but not yet in G2P. At least one variant reported in six cases from two unrelated families, together with supportive functional studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.265 | ATP5G3 | Arina Puzriakova edited their review of gene: ATP5G3: Added comment: This gene was recently included on a gene list provided by Carl Fratter (Oxford University Hospitals NHS Trust) on behalf of GMS Mitochondrial providers, indicating that the rating should be upgraded from Amber to Green on Mitochondrial panels (R357 and R63). As there is sufficient supporting evidence, the rating should also be updated to Green on this panel at the next GMS review.; Changed rating: GREEN; Changed publications to: 34636445, 34954817; Changed phenotypes to: Dystonia, early-onset, and/or spastic paraplegia, OMIM:619681; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.249 | SLC16A1 | Sarah Leigh edited their review of gene: SLC16A1: Changed phenotypes to: Erythrocyte lactate transporter defect, OMIM:245340, Hyperinsulinemic hypoglycemia, familial, 7, OMIM:610021, Monocarboxylate transporter 1 deficiency, OMIM:616095; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.249 | SLC16A1 | Sarah Leigh Phenotypes for gene: SLC16A1 were changed from Hyperinsulinemic hypoglycemia, familial, 7; mainly ketosis with borderline reduction in glucose to Erythrocyte lactate transporter defect, OMIM:245340; Hyperinsulinemic hypoglycemia, familial, 7, OMIM:610021; Monocarboxylate transporter 1 deficiency, OMIM:616095 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.243 | C19orf12 | Sarah Leigh edited their review of gene: C19orf12: Added comment: Monfrini et al (PMID: 29295770) and Gregory et al (PMID: 31087512) have reported heterozygous pathogenic C19ORF12 variants in patients with neurodegeneration with brain iron accumulation 4 (OMIM: 614298). Therefore, the mode of inheritance for this gene should be BOTH monoallelic and biallelic, autosomal or pseudoautosomal.; Changed publications to: 29295770, 31087512; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.238 | PEX6 | Sarah Leigh commented on gene: PEX6: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.237 | PNPT1 | Arina Puzriakova Phenotypes for gene: PNPT1 were changed from Deafness, autosomal recessive 70, 614934; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 13, 614932; respiratory chain disorder; hearing loss; Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) to Combined oxidative phosphorylation deficiency 13, OMIM:614932; Deafness, autosomal recessive 70, OMIM:614934; Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.236 | SPTLC1 | Sarah Leigh Added comment: Comment on mode of inheritance: There is no data to support that homozygous variants of SPTLC1 are associated with Neuropathy, hereditary sensory and autonomic, type IA, OMIM:162400. Therefore the MOI for this gene should be MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.219 | CPT2 | Arina Puzriakova Phenotypes for gene: CPT2 were changed from CPT deficiency, hepatic, type II 600649; CPT II deficiency, lethal neonatal 608836; Carnitine palmitoyltransferase II (CPTII) deficiency (Disorders of carnitine transport and the carnitine cycle) to CPT II deficiency, infantile, OMIM:600649; CPT II deficiency, lethal neonatal, OMIM:608836; CPT II deficiency, myopathic, stress-induced, OMIM:255110; Carnitine palmitoyltransferase II (CPTII) deficiency (Disorders of carnitine transport and the carnitine cycle) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.218 | XPNPEP3 | Sarah Leigh edited their review of gene: XPNPEP3: Added comment: Associated with relevant phenotype in OMIM and as limited Gen2Phen gene. At least three variants were reported in three unrelated cases (PMID: 32660933; 20179356). Two of the variants were terminating (RCV000000069, RCV001554332) and the third was a missense variant (RCV000000068), that seems to activate a cryptic splice site; RT-PCR of lymphoblastoid cells showed that this resulted in the inclusion of intronic bases and a frameshift. Cilia-related function was examined by the suppression of zebrafish xpnpep3, resulting in phenotypes reminiscent of ciliopathy morphants, this effect was rescued by human XPNPEP3 that was devoid of a mitochondrial localization signal (PMID: 20179356).; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.214 | MVK | Arina Puzriakova Phenotypes for gene: MVK were changed from Hyper-IgD syndrome 260920; Mevalonic aciduria 610377; Porokeratosis 3, multiple types 175900 to Hyper-IgD syndrome, OMIM:260920; Mevalonic aciduria, OMIM:610377; Porokeratosis 3, multiple types, OMIM:175900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.212 | SSBP1 |
Sarah Leigh changed review comment from: Comment on mode of inheritance: The moi for this gene could be changed to BOTH monoallelic and Biallelic as PMID: 34905022 reports a case of SSBP1-disease with biallelic SSBP1 variants.; to: Comment on mode of inheritance: The moi for this gene should be changed to BOTH monoallelic and Biallelic as PMID: 34905022 & 3155024 report two cases of SSBP1-disease associated with biallelic SSBP1 variants. The variant c.380G>A p.(Arg127Gln)(MAF of 0.00004) was found with c.394A>G p.(Ile132Val)(PMID: 34905022), which had previously been found as a homozygote in a single case (PMID: 31550240). |
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| Likely inborn error of metabolism - targeted testing not possible v2.211 | SSBP1 | Sarah Leigh Added comment: Comment on mode of inheritance: The moi for this gene could be changed to BOTH monoallelic and Biallelic as PMID: 34905022 reports a case of SSBP1-disease with biallelic SSBP1 variants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.206 | TARS2 | Sarah Leigh Added comment: Comment on publications: PMID: 24827421 - Compound heterozygous variants in TARS2 were reported in the proband and his affected sister - a missense mutation (c.845C>T, p.Pro282Leu) and a nucleotide change in position +3 of intron 6 (g.4255A>G, c.695+3A>G). The parents carrying one of the variants, one unaffected sister carried one variant, and the other unaffected sibling carried neither. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.206 | TARS2 | Sarah Leigh Publications for gene: TARS2 were set to PMID: 24827421 - Compound heterozygous variants in TARS2 were reported in the proband and his affected sister - a missense mutation (c.845C>T, p.Pro282Leu) and a nucleotide change in position +3 of intron 6 (g.4255A>G, c.695+3A>G). The parents carrying one of the variants, one unaffected sister carried one variant, and the other unaffected sibling carried neither. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.195 | GLS | Arina Puzriakova commented on gene: GLS: Added 'watchlist_MOI' tag to highlight monoallelic phenotype (MIM# 618339) which is also relevant to this panel, but as there is only a single case reported to date this is not yet sufficient to update the MOI. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.190 | ATXN7 |
Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN7. Tag currently-ngs-unreportable tag was added to gene: ATXN7. |
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| Likely inborn error of metabolism - targeted testing not possible v2.187 | EHHADH | Arina Puzriakova Added comment: Comment on list classification: Single family reported with additional functional data which is sufficient evidence to rate as Amber, awaiting further evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.181 | ACAT2 | Arina Puzriakova Added comment: Comment on list classification: New gene added by Andžela Lazdāne. Currently associated with a provisional phenotype in OMIM (?ACAT2 deficiency, OMIM:614055) and not yet listed in G2P. In the 2 cases reported to date (PMIDs: 20597, 6150136), diagnoses were made based on molecular rather than genetic findings. Rating Red as at present there is no published evidence of deleterious variants in the ACAT2 gene leading to this phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.147 | ALDH18A1 | Sarah Leigh commented on gene: ALDH18A1: The mode of inheritance for this gene should be BOTH monoallelic and biallelic, autosomal or pseudoautosomal, as reduced levels of proline, ornithine, arginine, and citrulline have been reported in cases with both monoallelic and biallelic ALDH18A1 variants (PMIDs 11092761; 22170564; 26320891). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.122 | NDUFB7 | Sarah Leigh Added comment: Comment on list classification: Comment on list classification: Not associated with relevant phenotype in OMIM or Gen2Phen. At least one biallelic splicing variant reported. RNA sequencing revealed that this variant disrupted normal splicing (PMID 33502047) and human knock-out cells have shown that NDUFB7 is one of the subunits strictly required for assembly of a functional mitochondrial complex I subunit, which is essential for cell viability (PMID 27626371). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.116 | NDUFA12 | Sarah Leigh edited their review of gene: NDUFA12: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least five variants reported in five unrelated cases, together with supportive studies. Phenotypic variability was evident in the cases reported (PMID: 21617257; 33715266).; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.65 | NDUFC2 | Sarah Leigh edited their review of gene: NDUFC2: Added comment: Associated with relevant phenotype in OMIM, but not Gen2Phen. At least 2 variants have been reported in two unrelated cases, together with supportive functional evidence (PMID 32969598). There are also 2 families with complex I deficiency with reported by Carl Fratter (10 May 2019, Oxford University Hospitals NHS Trust).; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.59 | GORAB |
Sarah Leigh edited their review of gene: GORAB: Added comment: PMID 30631079 demonstrates that disrupting variants in GORAB result in "impairment of COPI-mediated retrieval of trans-Golgi enzymes, resulting in a deficit in glycosylation of secretory cargo proteins. Our results therefore identify GORAB as a COPI scaffolding factor". The authors conclude that this finding supports the view that "defective protein glycosylation is a major disease mechanism in gerodermia osteodysplastica". Therefore variants in GORAB are relevant to this panel based on this mechanism.; Changed rating: GREEN |
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| Likely inborn error of metabolism - targeted testing not possible v2.50 | GLS_GCA |
Arina Puzriakova Added comment: Comment on list classification: There are sufficient unrelated cases and supportive functional data for inclusion as diagnostic-grade. However, detection of this 5' UTR triplet expansion must first be validated within the Genomics England pipeline. In the meantime, rating Red but will raise the STR for validation with the Rare Disease team. |
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| Likely inborn error of metabolism - targeted testing not possible v2.48 | GLS |
Arina Puzriakova Added comment: Comment on list classification: There are sufficient cases, supported by functional data, to rate this gene Green - however, detection of the 5' UTR triplet expansion (PMID:30970188) has not yet been validated within the Genomics England pipeline. When excluding cases with the STR, the remaining evidence is not sufficient for inclusion as diagnostic-grade and therefore this gene is tagged 'for-review' to assess whether it should be downgraded to Amber until the STR is validated or additional cases arise. |
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| Likely inborn error of metabolism - targeted testing not possible v2.45 | GLS | Arina Puzriakova Added comment: Comment on mode of inheritance: As evidence for pathogenicity of monoallelic variants is limited (currently only 1 case), MOI will remain as 'Biallelic' until further cases emerge that support an association between monoallelic variants and disease. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.41 | NUS1 | Eleanor Williams edited their review of gene: NUS1: Added comment: Provisionally associated with ?Congenital disorder of glycosylation, type 1aa #617082 (AR) in OMIM based on family reported in Park et al 2014 (PMID: 25066056). They describe a family of Roma origin in which 2 out of 4 siblings presented with congenital scoliosis, severe neurological impairment, refractory epilepsy, hearing deficit and visual impairment with discrete bilateral macular lesions. A homozgyous missense mutation, R290H, was found in NUS1 (called NGBR in the paper) by exome sequencing. It segregated with the disease in the family. Patient fibroblasts showed reduced dolichol profiles and enhanced accumulation of free cholesterol as do fibroblasts from mice lacking NgBR.; Changed publications: 25066056; Changed phenotypes: ?Congenital disorder of glycosylation, type 1aa OMIM:617082, congenital disorder of glycosylation, type IAA MONDO:0014904 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.35 | HS2ST1 |
Ivone Leong gene: HS2ST1 was added gene: HS2ST1 was added to Inborn errors of metabolism. Sources: Literature for-review tags were added to gene: HS2ST1. Mode of inheritance for gene: HS2ST1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HS2ST1 were set to 33159882 Phenotypes for gene: HS2ST1 were set to Intellectual disability; dysmorphic features; congenital anomalies Review for gene: HS2ST1 was set to AMBER Added comment: This gene is not associated with a relevant phenotype in OMIM or Gene2Phenotype. Only 2 of 3 unrelated families with affected individuals described in PMID: 33159882 were reported to have ID. The affected individuals in the third family could not be assessed for ID. Other features affected individuals had were muscular hypotonia, hypoplasia/agenesis of corpus callosum, skeletal abnormalities, uni/bilateral renal agenesis (2/3) and craniofacial dysmorphism. This gene should be considered for Green gene rating status at the next review. Sources: Literature |
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| Likely inborn error of metabolism - targeted testing not possible v2.25 | GALM |
Ivone Leong gene: GALM was added gene: GALM was added to Inborn errors of metabolism. Sources: Expert Review,Literature for-review tags were added to gene: GALM. Mode of inheritance for gene: GALM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GALM were set to 30451973; 30910422 Phenotypes for gene: GALM were set to Galactosemia IV, 618881 Review for gene: GALM was set to GREEN Added comment: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with an appropriate phenotype in OMIM but not in Gene2Phenotype. There is enough evidence for this gene to be Green. The gene has been given an Amber rating and will be promoted to Green at the next review. Review from Zornitza Stark (Australian Genomics) on the Cholestasis panel: Homozygous and compound heterozygous variants (missense, nonsense and frameshift) found in 8 Japanese patients from unrelated families with unexplained galactosaemia. (No variants in GALT, GALK1, and GALE). In vitro expression analysis and enzyme activity assay of the patients’ peripheral blood mononuclear cells showed total lack of or compromised expression of GALM protein. One homozygote for one of these variants p.(Gly142Arg) in gnomAD (African population). (Wada, Y. et al 2019; PMID: 30451973) Note only two individuals were reported as having transient cholestasis. Sources: Literature Zornitza Stark (Australian Genomics), 2 May 2020 Sources: Expert Review, Literature |
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| Likely inborn error of metabolism - targeted testing not possible v2.24 | SLC5A6 | Sarah Leigh changed review comment from: Comment on list classification: Based on five variants in three unrelated cases, together with supportive aminal model studies.; to: Comment on list classification: Based on five variants in three unrelated cases, together with supportive animal model studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.14 | ALG14 | Sarah Leigh Added comment: Comment on list classification: Associated with Myasthenic syndrome, congenital, 15, without tubular aggregates 616227 in OMIM, but not associated with phenotype in Gen2Phen. At least 6 variants reported in at least 5 cases with varying phenotypes. PMID 23404334 reports compound heterozygous (p.P65L, P.R104*) sibs, who manifested with myasthenic syndromes, but did not have intellectural disability nor seizures and were 62 and 51 years old when reported. PMID 28733338 reports two compound heterozygous (p.D74N, pV141G), (p.D74N, p.R109Q) cases and a homozygous (p.D74N), with early and lethal neurodegeneration with myasthenic and myopathic features, but the cases died before intellectual disability was manifiest. However, seizures were evident in two compound heterozygous families. PMID 30221345 reports a homozygous splicing variant in a case with intellectual disability and seizures. Functional studies were presented showing that this variant resulting in exon skipping, however, this was not completely prenetrant as wild type protein was detected at a low level in the patient. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.12 | ISCU |
Sarah Leigh changed review comment from: Comment on mode of inheritance: PMID 29079705 reports a novel de novo dominant variant in ISCU associated with mitochondrial myopathy, which justifies the mode of inheritance recorded here.; to: Comment on mode of inheritance: Comment on mode of inheritance: PMID 29079705 reports a novel de novo dominant variant missense p.G97V variant has been reported and therefore this may represent a specific mechanism of action. Further evidence is needed to determine which (if any) other monoallelic variants will cause disease beyond mitochondrial myopathy, which justifies the mode of inheritance recorded. |
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| Likely inborn error of metabolism - targeted testing not possible v2.10 | SLC5A6 | Sarah Leigh Added comment: Comment on list classification: Based on five variants in three unrelated cases, together with supportive aminal model studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v2.9 | SLC5A6 |
Sarah Leigh gene: SLC5A6 was added gene: SLC5A6 was added to Inborn errors of metabolism. Sources: Literature Mode of inheritance for gene: SLC5A6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC5A6 were set to 27904971; 31392107; 31754459; 23104561; 29669219 Phenotypes for gene: SLC5A6 were set to SLC5A6-related Neurodevelopmental Disorder Review for gene: SLC5A6 was set to GREEN Added comment: Not associated with phenotype in OMIM and as possible Gen2Phen gene for SLC5A6-related Neurodevelopmental Disorder. At least 5 variants published in three unrelated famililies (4 cases total) with SLC5A6-related Neurodevelopmental Disorder, together with supportive functional studies (PMID 29669219; 23104561). One of the cases had mixed semiology seizures including focal dyscognitive, absence, tonic spasms and generalised convulsive seizures with electrographic features of encephalopathy with generalised and independent multifocal spike-wave discharges (PMID 31754459), another case had brain, immune, bone and intestinal dysfunction (PMID 27904971) and the third had metabolic dysfunction mimicking biotinidase deficiency (PMID 31392107). This condition could be treated with biotin supplementation and introduction of pantothenic acid supplementation (PMID 31392107). Sources: Literature |
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| Likely inborn error of metabolism - targeted testing not possible v2.1 | PCYT2 |
Sarah Leigh edited their review of gene: PCYT2: Added comment: Vaz et al. (2019 - PMID: 31637422 - DDD study among the co-authors) report on 5 individuals - from 4 families - with biallelic PCYT2 mutations. The phenotype corresponded to a complex hererditary paraplegia with global DD, regression (4/5), ID (mild in 3/5, severe in 2/5), spastic para-/tetraparesis, epilepsy (5/5 - variable onset 2-16 yrs - focal or tonic-clonic seizures) and progressive cerebral and cerebellar atrophy. Exome sequencing in all revealed biallelic PCYT2 variants, confirmed with Sanger s. in probands and their parents (NM_001184917.2 - corresponding to the canonical transcript used as Ref below): - P1 (Fam1) : 2 missense SNVs in trans configuration, c.730C>T or p.His244Tyr and c.920C>T or p.Pro307Leu - P2 (Fam2 - consanguineous of White British origin), P3 (Fam3 - Consanguineous of Turkish origin), P4,5 (Fam4 - consanguineous, unspecified origin) : homozygosity for c.1129C>T or p.Arg377Ter) affecting the last exon of 8/12 transcripts, including the canonical one. Individuals with the same genotype displayed variable degrees of ID (eg P3 - severe / P2, P4,5 - mild ID). For sibs in Fam4, homozygosity for a missense SACS variant led to consideration of the respective disorder (AR spastic ataxia of Charlevoix-Saguenay) though the variant was predicted to be tolerated in silico and notably the MRI images not suggestive. All variants were absent from / had extremely low AF in public databases, with no homozygotes. Posphatidylethanolamine (PE) is a membrane lipid, particularly enriched in human brain (45% of phospholypid fraction). PE is synthesized either via the CDP-ethanolamine pathway or by decarboxylation of phosphatidylserine in mitochondria. PCYT2 encodes CTP:phosophoethanolamine cytidyltransferase (ET) which is an ubiquitously expressed rate-limiting enzyme for PE biosynthesis in the former pathway. In silico, the 2 missense variants - localizing in the CTP catalytic domain 2 - were predicted to be damaging, as well as to affect protein stability. Fibroblasts of 3 patients (P1, P2, P3) representing all variants were studied: - Enzymatic activity was shown to be significantly reduced (though not absent) compared to controls. Abnormalities were noted upon Western Blot incl. absence in all 3 patients studied of one of the 2 bands normally found in controls (probably representing the longer isoform), reduced intensity in all 3 of another band probably corresponding to a shorter isoform, and presence of an additional band of intermediate molec. mass in patients with the truncating variant. - RT-PCR on mRNA from patient fibroblasts did not reveal (significant) reduction compared to controls. - Lipidomic profile of patient fibroblasts was compatible with the location of the block in the phospholipid biosynthesis pathway and different from controls. The lipidomic profile had similarities with what has been reported for EPT1 deficiency, the enzyme directly downstream of ET. The SELENO1-related phenotype (/EPT1 deficiency) is also highly overlapping. CRISPR-Cas9 was used to generate pcyt2 partial or complete knockout (ko) zebrafish, targeting either the final (ex13) or another exon (ex3) respectively. mRNA expression was shown to be moderately reduced in the first case and severely reduced/absent in the second, compared to wt. Similarly, complete-ko (ex3) led to significantly lower survival, with impaired though somewhat better survival of partial-ko (ex13) zebrafish. Complete knockout of Pcyt2 in mice is embryonically lethal (PMID cited: 17325045) while heterozygous mice develop features of metabolic syndrome (PMID cited: 22764088). Given lethality in knockout zebrafish / mice and the residual activity (15-20%) in patient fibroblasts, the variants reported were thought to be hypomorphic and complete loss of function possibly incompatible with life. PCYT2 is not associated with any phenotype in OMIM/G2P/SysID and not commonly included in gene panels for ID. As a result this gene could included in the ID / epilepsy panels with green (~/>3 indiv/fam/variants with the nonsense found in different populations, consistent phenotype, lipidomics, in silico/in vitro/in vivo evidence) or amber rating. [Please consider inclusion in other possibly relevant panels eg. for metabolic disorders, etc]. Sources: Literature Konstantinos Varvagiannis (Other), 11 Nov 2019; Changed rating: GREEN |
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| Likely inborn error of metabolism - targeted testing not possible v1.425 | PDK3 |
Sarah Leigh changed review comment from: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 2 variants reported in at least three unrelated cases, together with functional studies.; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 2 variants reported in at least three unrelated cases, together with functional studies. The phenotype of ?Charcot-Marie-Tooth disease, X-linked dominant, 6 300905, is not relevant to the "Inborn errors of metabolism" panel, which is why it is rated Amber (clinical opinion of Helen Britain, GEL Clinical Fellow). |
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| Likely inborn error of metabolism - targeted testing not possible v1.422 | UPB1 | Ellen McDonagh changed review comment from: Additional comments were provided by Dr Clare Beesley and colleagues (Great Ormond Street Hospital for Children NHS Foundation Trust) as part of the GMS Metabolic Specialist disease test group: 16 mutations reported in HGMD & several families have been reported in the literature. Heterologous expression of A85E mutant enzyme in E. coli yielded no residual activity (Van Kuilenburg et al., 2004, PMID: 15385443].; to: Additional comments were provided by Dr Clare Beesley and colleagues (Great Ormond Street Hospital for Children NHS Foundation Trust) as part of the GMS Metabolic Specialist disease test group: 16 mutations reported in HGMD & several families have been reported in the literature. Heterologous expression of A85E mutant enzyme in E. coli yielded no residual activity (Van Kuilenburg et al., 2004, PMID: 15385443). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.422 | UPB1 | Ellen McDonagh commented on gene: UPB1: Additional comments were provided by Dr Clare Beesley and colleagues (Great Ormond Street Hospital for Children NHS Foundation Trust) as part of the GMS Metabolic Specialist disease test group: 16 mutations reported in HGMD & several families have been reported in the literature. Heterologous expression of A85E mutant enzyme in E. coli yielded no residual activity (Van Kuilenburg et al., 2004, PMID: 15385443]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.422 | TMEM199 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to feedback from the GMS Metabolic Specialist disease test group: 4 patients from 3 unrelated families reported in the literature. All patients had a type 2 pattern on serum transferrin isoelectric focusing (IEF), indicating abnormal N-glycosylation, as well as abnormal IEF of ApoC-III, indicating abnormal O-glycosylation (PMID:26833330). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.420 | BCAT2 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to expert review from representation of the GMS Metabolic disease specialist test group; multiple cases reported and this is a treatable. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.413 | GLS | Ellen McDonagh Added comment: Comment on list classification: Due to expert review, evidence of 2 unrelated families for loss-of-function variants and further evidence for the role of this gene with an STR reported, this gene has been promoted from Red to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.411 | GLS | Ellen McDonagh Added comment: Comment on publications: PMID: 30575854 - 2 families reported with 4 infants who had homozyous/compound heterozygous loss-of-function variants in this gene resulting in early neonatal epileptic encephalopathy with glutaminase deficiency and a lethal outcome. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.411 | GLS | Ellen McDonagh Added comment: Comment on publications: PMID: 30575854 - 2 families reported with 4 infants who had homozyous/compound heterozygous loss-of-function variants in this gene resulting in early neonatal epileptic encephalopathy with glutaminase deficiency and a lethal outcome. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.410 | GLS | Ellen McDonagh Added comment: Comment on publications: PMID: 30970188 - short tandem repeat (STR) reported in this gene to cause an inborn error of metabolism. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.406 | SLC25A32 | Catherine Snow commented on gene: SLC25A32: Treatable tag was added based on reports in PMID: 26933868 and 28443623, that riboflavin treatment was effective. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.406 | NSUN3 | Catherine Snow changed review comment from: PMID: 27356879 - reports on a loss-of-function mutation in NSUN3 in a patient presenting with combined mitochondrial respiratory chain complex deficiency.; to: PMID: 27356879 - reports on a compound heterozygous variant resulting in a loss-of-function mutation in NSUN3 in a patient presenting with combined mitochondrial respiratory chain complex deficiency. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.398 | UQCC2 | Catherine Snow Added comment: Comment on list classification: This gene was promoted from Amber to Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter. Two unrelated cases reported, with functional supporting evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.397 | UQCC2 | Catherine Snow Added comment: Comment on list classification: This gene was promoted from Amber to Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter. Two unrelated cases reported, with functional supporting evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.346 | TCN2 | Catherine Snow Added comment: Comment on publications: There are >3 unrelated cases reported in the literature. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.345 | TAT |
Catherine Snow Added comment: Comment on publications: PMID: 28255985 Reports on 106 families, represented by 143 individuals, carrying a total of 36 genetic variants. Variants include large deletions, non‐synonymous and nonsense amino‐acid changes, frameshifts and splice variants. |
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| Likely inborn error of metabolism - targeted testing not possible v1.336 | ISCA2 |
Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in two different ethinicities. Rated green based on review of Anna de Burca (Clinical Fellow, Genomic England). |
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| Likely inborn error of metabolism - targeted testing not possible v1.331 | SLC2A1 |
Ivone Leong Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Promoted from Amber to Green. SLC2A1 is associated with GLUT1 deficiency syndrome 1 and GLUT1 deficiency syndrome 2 on OMIM and Gene2Phenotype. There are >3 unrelated cases reported on OMIM. Therefore, there is enough evidence for this gene to be promoted to Green status. |
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| Likely inborn error of metabolism - targeted testing not possible v1.330 | HSPA9 |
Sarah Leigh Added comment: Comment on phenotypes: EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia;Epiphyseal, Vertebral, Ear, Nose, plus associated findings. Monoallelic variants reported in Anemia, sideroblastic, 4 182170. |
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| Likely inborn error of metabolism - targeted testing not possible v1.329 | HSPA9 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in two unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.323 | COX8A |
Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 1 variant reported in a 12.5-year old girl, born of Turkish parents who were likely distantly related, with mitochondrial complex I deficiency. No further variants reported to date (30/09/2019).; to: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 1 variant reported in a 12.5-year old girl, born of Turkish parents who were likely distantly related, with mitochondrial complex I deficiency. The proband died from cardiorespiratory failure associated with infection and metabolic crisis at 12.5 years. No further variants reported to date (30/09/2019). |
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| Likely inborn error of metabolism - targeted testing not possible v1.323 | COX8A |
Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 1 variant reported in a 12.5-year old girl, born of Turkish parents who were likely distantly related, with mitochondrial complex I deficiency. No further variants reported to date (30/09/2019). |
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| Likely inborn error of metabolism - targeted testing not possible v1.321 | COQ7 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 2 variants reported in unrelated cases, together with supportive functional studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.315 | TMEM126A | Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with the phenotype Optic atrophy 7 612989 in OMIM, but not associated with phenotype in Gen2Phen. At least 2 variants reported in unrelated cases. The red rating is based on Helen Britain's opinion that, the phenotype of Optic atrophy 7 612989 will not present via a metabolic team. TMEM126A is green on the Optic neuropathy panel | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.313 | PDK3 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 2 variants reported in at least three unrelated cases, together with functional studies. |
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| Likely inborn error of metabolism - targeted testing not possible v1.312 | PDK3 | Sarah Leigh Added comment: Comment on mode of pathogenicity: A gain of function mechanism has been reported for the p.R158H variant, resulting in a more activity than the wild-type kinase (PMID: 23297365). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.311 | COX4I2 |
Sarah Leigh changed review comment from: Comment on list classification: This gene should remain Amber due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter. One homozygous variant (c.412G>A, p.E138K) reported in 5 Arab Muslim patients with exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis (612714) (PMID 19268275) and heterozygous variant (c.253C>T, p.R85W) found together with a heterozygous COX10 variant (c.1096G>T, p.V366L)(PMID 22592081).; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. This gene should remain Amber due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter. One homozygous variant (c.412G>A, p.E138K) reported in 5 Arab Muslim patients with exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis (612714) (PMID 19268275) and heterozygous variant (c.253C>T, p.R85W) found together with a heterozygous COX10 variant (c.1096G>T, p.V366L)(PMID 22592081). |
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| Likely inborn error of metabolism - targeted testing not possible v1.311 | COA5 | Sarah Leigh changed review comment from: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. No additional variants have been reported to date.; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with phenotype in OMIM and as a possible G2P. At least 1 variant reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.311 | COA5 | Sarah Leigh changed review comment from: Comment on list classification: No additional variants have been reported to date.; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. No additional variants have been reported to date. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.311 | ATP5E | Sarah Leigh changed review comment from: Comment on list classification: Based on Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: 1 reported case with functional studies.; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Based on Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: 1 reported case with functional studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.299 | COX4I2 |
Sarah Leigh Added comment: Comment on list classification: This gene should remain Amber due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter. One homozygous variant (c.412G>A, p.E138K) reported in 5 Arab Muslim patients with exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis (612714) (PMID 19268275) and heterozygous variant (c.253C>T, p.R85W) found together with a heterozygous COX10 variant (c.1096G>T, p.V366L)(PMID 22592081). |
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| Likely inborn error of metabolism - targeted testing not possible v1.289 | ATP5E | Sarah Leigh Added comment: Comment on list classification: Based on Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: 1 reported case with functional studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.286 | SPTLC1 |
Catherine Snow changed review comment from: Promoted from Amber to Green. This gene is associated with a relevant disease in OMIM and there is enough evidence to support a gene-disease association. SPTLC1, encodes one of the two subunits of serine palmitoyltransferase (SPT), the enzyme catalyzing the first and rate-limiting step in the de novo synthesis of sphingolipids. PMID 20097765 reports that mutations in SPTLC1 cause a gain of function mechanism, which results in the formation of two atypical and neurotoxic sphingolipid metabolites. Confirmed cases in Bristol (see review on Hereditary Neuropathy panel https://panelapp.genomicsengland.co.uk/panels/85/) and in sufficient publications.; to: Promoted from Amber to Green. This gene is associated with a relevant disease in OMIM and there is enough evidence to support a gene-disease association. SPTLC1, encodes one of the two subunits of serine palmitoyltransferase (SPT), the enzyme catalyzing the first and rate-limiting step in the de novo synthesis of sphingolipids. PMID 20097765 reports that mutations in SPTLC1 cause a gain of function mechanism, which results in the formation of two atypical and neurotoxic sphingolipid metabolites. Confirmed cases in Bristol (see review on Hereditary Neuropathy panel https://panelapp.genomicsengland.co.uk/panels/85/) and in sufficient publications. This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. |
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| Likely inborn error of metabolism - targeted testing not possible v1.281 | SPTLC2 |
Catherine Snow changed review comment from: Promoted from Amber to Green. This gene is associated with a relevant disease on OMIM and Gene2Phenotype and there is enough evidence to support a gene-disease association. SPTLC2, encodes one of the two subunits of serine palmitoyltransferase (SPT), the enzyme catalyzing the first and rate-limiting step in the de novo synthesis of sphingolipids. PMID: 20920666 reports on three heterozygous missense mutations in the SPTLC2 subunit of SPT in four families and also confirmed cases in Bristol (see review on Hereditary Neuropathy panel https://panelapp.genomicsengland.co.uk/panels/85/). This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.; to: Promoted from Amber to Green. This gene is associated with a relevant disease on OMIM and Gene2Phenotype and there is enough evidence to support a gene-disease association. SPTLC2, encodes one of the two subunits of serine palmitoyltransferase (SPT), the enzyme catalyzing the first and rate-limiting step in the de novo synthesis of sphingolipids. PMID: 20920666 reports on three heterozygous missense mutations in the SPTLC2 subunit of SPT in four families and also confirmed cases in Bristol (see review on Hereditary Neuropathy panel https://panelapp.genomicsengland.co.uk/panels/85/). This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. |
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| Likely inborn error of metabolism - targeted testing not possible v1.278 | IER3IP1 | Sarah Leigh changed review comment from: Comment on list classification: IER3IP1 has been demoted to Red on the Mitochondrial disorders panel on the recommendation of the GMS mitochondrial specialist test group, including by Carl Fratter (Oxford University Hospitals NHS Trust). It is associated with Microcephaly, epilepsy, and diabetes syndrome 614231, which is not technically a mitochondrial disorder, as the phenotype is quite different to other mitochondrial conditions, thus in the opinion of Helen Britain the phenotypes reported, the condition could initially present as a mimic of a mitochondrial presentation e.g. abnormal liver enzymes, diabetes, neurological dysfunction and therefore a green rating on metabolic panels would seem appropriate.; to: Comment on list classification: IER3IP1 has been demoted to Red on the Mitochondrial disorders panel on the recommendation of the GMS mitochondrial specialist test group, including by Carl Fratter (Oxford University Hospitals NHS Trust). It is associated with Microcephaly, epilepsy, and diabetes syndrome 614231, which is not technically a mitochondrial disorder, as the phenotype is quite different to other mitochondrial conditions. Thus in the opinion of Helen Britain (Genomics England Clinical Fellow) the phenotypes reported could initially present as a mimic of a mitochondrial presentation e.g. abnormal liver enzymes, diabetes, neurological dysfunction and therefore a green rating on metabolic panels would seem appropriate. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.278 | IER3IP1 | Sarah Leigh changed review comment from: Comment on list classification: IER3IP1 is being demoted to Red on this panel on the recommendation of the GMS mitochondrial specialist test group, including by Carl Fratter (Oxford University Hospitals NHS Trust). As it is associated with Microcephaly, epilepsy, and diabetes syndrome 614231, which is not technically a mitochondrial disorder, as the phenotype is quite different to other mitochondrial conditions.; to: Comment on list classification: IER3IP1 has been demoted to Red on the Mitochondrial disorders panel on the recommendation of the GMS mitochondrial specialist test group, including by Carl Fratter (Oxford University Hospitals NHS Trust). It is associated with Microcephaly, epilepsy, and diabetes syndrome 614231, which is not technically a mitochondrial disorder, as the phenotype is quite different to other mitochondrial conditions, thus in the opinion of Helen Britain the phenotypes reported, the condition could initially present as a mimic of a mitochondrial presentation e.g. abnormal liver enzymes, diabetes, neurological dysfunction and therefore a green rating on metabolic panels would seem appropriate. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.278 | SLC2A1 | Ivone Leong Phenotypes for gene: SLC2A1 were changed from Intellectual disability; Early onset dystonia; Cataracts; Glucose transporter 1 deficiency (blood-brain barrier) (Disorders of glucose transport); Hereditary ataxia; Epileptic encephalopathy; Familial Genetic Generalised Epilepsies to Intellectual disability; Early onset dystonia; Cataracts; Glucose transporter 1 deficiency (blood-brain barrier) (Disorders of glucose transport); Hereditary ataxia; Epileptic encephalopathy; Familial Genetic Generalised Epilepsies; GLUT1 deficiency syndrome 1, infantile onset, severe, 606777; GLUT1 deficiency syndrome 2, childhood onset, 612126 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.277 | SC5D |
Ivone Leong Added comment: Comment on list classification: Promoted from Amber to Green. This gene is associated with a relevant disease on OMIM and Gene2Phenotype and there is enough evidence to support a gene-disease association. This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. |
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| Likely inborn error of metabolism - targeted testing not possible v1.273 | RNASEH2B |
Ivone Leong changed review comment from: Comment on list classification: Demoted from Amber to Red. RNASEH2B is associated with Aicardi-Goutieres syndrome 2 on OMIM and Gene2Phenotype. There are 2 unrelated cases on OMIM supporting the gene-disease link between RNASEH2B with Aicardi-Goutieres syndrome; however, RNASEH2B does not appear to be associated with a metabolic phenotype. Therefore this gene has been demoted to red. This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.; to: Comment on list classification: Demoted from Amber to Red. RNASEH2B is associated with Aicardi-Goutieres syndrome 2 on OMIM and Gene2Phenotype. There are 2 unrelated cases on OMIM about RNASEH2B causing Aicardi-Goutieres syndrome; however, RNASEH2B does not appear to be associated with a metabolic phenotype. Therefore this gene has been demoted to red. This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. |
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| Likely inborn error of metabolism - targeted testing not possible v1.273 | RNASEH2B |
Ivone Leong Added comment: Comment on list classification: Demoted from Amber to Red. RNASEH2B is associated with Aicardi-Goutieres syndrome 2 on OMIM and Gene2Phenotype. There are 2 unrelated cases on OMIM supporting the gene-disease link between RNASEH2B with Aicardi-Goutieres syndrome; however, RNASEH2B does not appear to be associated with a metabolic phenotype. Therefore this gene has been demoted to red. This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. |
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| Likely inborn error of metabolism - targeted testing not possible v1.271 | RNASEH2A | Ivone Leong changed review comment from: RNASEH2A is associated with Aicardi-Goutieres syndrome 4 on OMIM and Gene2Phenotype. RNASEH2A does not appear to be associated with a metabolic phenotype. Therefore this gene will remain Amber.; to: RNASEH2A is associated with Aicardi-Goutieres syndrome 4 on OMIM and Gene2Phenotype. There are >3 unrelated cases on OMIM supporting the gene-disease link between RNASEH2A with Aicardi-Goutieres syndrome; however, RNASEH2A does not appear to be associated with a metabolic phenotype. Therefore this gene has been demoted to red. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.265 | CYP7B1 | Sarah Leigh changed review comment from: Comment on list classification: Although there is enough evidence for an association with Spastic paraplegia 5A, autosomal recessive 270800, only one variant has been reported in Bile acid synthesis defect, congenital, 3 613812, which is the more relevant phenotype for metabolic panels.; to: Comment on list classification: Although there is enough evidence for an association with Spastic paraplegia 5A, autosomal recessive 270800, only one variant has been reported in 3 unrelated cases of Bile acid synthesis defect, congenital, 3 613812, which is the more relevant phenotype for metabolic panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.265 | CYP7B1 | Sarah Leigh Added comment: Comment on list classification: Although there is enough evidence for an association with Spastic paraplegia 5A, autosomal recessive 270800, only one variant has been reported in Bile acid synthesis defect, congenital, 3 613812, which is the more relevant phenotype for metabolic panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.255 | ALDH3A2 | Sarah Leigh commented on gene: ALDH3A2: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 9 variants reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.255 | ALAS2 | Sarah Leigh commented on gene: ALAS2: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with phenotype in OMIM and not in Gen2Phen. At least 18 variants identified in Anemia, sideroblastic, 1 300751 and two variants in Protoporphyria, erythropoietic, X-linked 300752 in six unrelated families, together with functional studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.255 | ADSL | Sarah Leigh commented on gene: ADSL: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 8 variants reported associated with adenylosuccinase deficiency in at least 10 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.255 | ADA | Sarah Leigh commented on gene: ADA: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 30 variants reported associated with Adenosine deaminase deficiency. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.255 | ACY1 | Sarah Leigh commented on gene: ACY1: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in at least 9 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.254 | ALAS2 | Sarah Leigh edited their review of gene: ALAS2: Added comment: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with phenotype in OMIM and not in Gen2Phen. At least 18 variants identified in Anemia, sideroblastic, 1 300751 and two variants in Protoporphyria, erythropoietic, X-linked 300752 in six unrelated families, together with functional studies.; Changed rating: GREEN; Changed publications: 27604308, 1570328, 7560104, 12663458, 18760763; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.252 | PSAT1 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for ?Phosphoserine aminotransferase deficiency 610992; Neu-Laxova syndrome 2 616038. At least 5 variants reported in 6 cases of Neu-Laxova syndrome 2 616038 and 2 variants in a case of ?Phosphoserine aminotransferase deficiency 610992. |
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| Likely inborn error of metabolism - targeted testing not possible v1.248 | PRPS1 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for Arts syndrome 301835, Charcot-Marie-Tooth disease, X-linked recessive, 5 311070, Deafness, X-linked 1 304500 and Phosphoribosylpyrophosphate synthetase superactivity 300661. At least 22 variants have been reported across the phenotypes. |
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| Likely inborn error of metabolism - targeted testing not possible v1.242 | POR | Sarah Leigh Publications for gene: POR were set to 27604308 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.241 | POR | Sarah Leigh Classified gene: POR as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.241 | POR |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 10 variants associated with Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis 201750 and 6 variants associated with Disordered steroidogenesis due to cytochrome P450 oxidoreductase 613571. |
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| Likely inborn error of metabolism - targeted testing not possible v1.241 | POR | Sarah Leigh Gene: por has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.239 | POR | Sarah Leigh Phenotypes for gene: POR were changed from Antley-Bixler syndrome with disordered steroidogenesis; Unexplained skeletal dysplasia; Disorders of sex development; Craniosynostosis syndromes phenotypes to Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis 201750; Disordered steroidogenesis due to cytochrome P450 oxidoreductase 613571 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.237 | PNP |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 10 variants reported. |
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| Likely inborn error of metabolism - targeted testing not possible v1.237 | PNP |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 10 variants reported. |
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| Likely inborn error of metabolism - targeted testing not possible v1.235 | PINK1 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 12 variants were reported. |
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| Likely inborn error of metabolism - targeted testing not possible v1.232 | PIGM |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 1 variant was reported in 2 unrelated families (PMID 16767100), together with supportive functional studies (PMID 17442906 & 25293775). |
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| Likely inborn error of metabolism - targeted testing not possible v1.231 | PIGM |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 1 variant was reported in 2 unrelated families (PMID 16767100), together with supportive functional studies (PMID 17442906 & 25293775). |
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| Likely inborn error of metabolism - targeted testing not possible v1.231 | PIGM |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 1 variant was reported in 2 unrelated families (PMID 16767100), together with supportive functional studies (PMID 17442906 & 25293775). |
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| Likely inborn error of metabolism - targeted testing not possible v1.226 | PHGDH |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for both phenotypes. At least 6 variants reported in 6 unrelated cases of Phosphoglycerate dehydrogenase deficiency 601815 and 4 variants reported in 4 unrelated cases of Neu-Laxova syndrome 1 256520. |
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| Likely inborn error of metabolism - targeted testing not possible v1.222 | PEPD |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 11 variants reported. |
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| Likely inborn error of metabolism - targeted testing not possible v1.222 | PEPD |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 11 variants reported. |
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| Likely inborn error of metabolism - targeted testing not possible v1.220 | PDPR |
Sarah Leigh changed review comment from: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 1 variant reported in a case of global developmental delay, typical Joubert syndrome, according to PMID 25558065.; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Not associated with a phenotype in OMIM or in Gen2Phen. At least 1 variant reported in a case of global developmental delay, typical Joubert syndrome, according to PMID 25558065. |
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| Likely inborn error of metabolism - targeted testing not possible v1.219 | PDPR |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 1 variant reported in a case of global developmental delay, typical Joubert syndrome, according to PMID 25558065. |
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| Likely inborn error of metabolism - targeted testing not possible v1.214 | PCSK9 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 gain of function variants reported in unrelated cases of Hypercholesterolemia, familial, 3 603776 and at least 5 loss of function variants have been reported in unrelated cases of {Low density lipoprotein cholesterol level QTL 1} 603776. |
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| Likely inborn error of metabolism - targeted testing not possible v1.211 | PCK1 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in unrelated cases. |
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| Likely inborn error of metabolism - targeted testing not possible v1.210 | PCK1 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in unrelated cases. |
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| Likely inborn error of metabolism - targeted testing not possible v1.210 | PCK1 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in unrelated cases. |
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| Likely inborn error of metabolism - targeted testing not possible v1.205 | PANK2 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 13 variants reported for Neurodegeneration with brain iron accumulation 234200 and 3 variants in 2 unrelated cases of HARP syndrome 607236. |
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| Likely inborn error of metabolism - targeted testing not possible v1.205 | PANK2 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 13 variants reported for Neurodegeneration with brain iron accumulation 234200 and 3 variants in 2 unrelated cases of HARP syndrome 607236. |
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| Likely inborn error of metabolism - targeted testing not possible v1.202 | OPLAH |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants have been reported. It is not clear whether the mode of inheritance is biallelic or monoallelic as homozygous and heterozygote cases have been seen. The PMID 21651516 reports two sibs who are homozygous for a terminating variant, the younger brother is 5-oxoprolinase deficiency, however, his clinically unaffected sister just has increased 5-oxoproline excretion. |
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| Likely inborn error of metabolism - targeted testing not possible v1.200 | OCRL |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for both Dent disease 2 300555 and Lowe syndrome 309000. At least 5variants reported in Dent disease 2 300555 and 4 variants in Lowe syndrome 309000. |
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| Likely inborn error of metabolism - targeted testing not possible v1.200 | OCRL |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for both Dent disease 2 300555 and Lowe syndrome 309000. At least 5variants reported in Dent disease 2 300555 and 4 variants in Lowe syndrome 309000. |
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| Likely inborn error of metabolism - targeted testing not possible v1.199 | OCRL | Sarah Leigh Added comment: Comment on phenotypes: Lowe syndrome (Disorders of amino acid transport);Renal tract calcification (or Nephrolithiasis/nephrocalcinosis);Intellectual disability;Intellectual_disability;Cataracts | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.199 | OCRL | Sarah Leigh Added comment: Comment on phenotypes: Lowe syndrome (Disorders of amino acid transport);Renal tract calcification (or Nephrolithiasis/nephrocalcinosis);Intellectual disability;Intellectual_disability;Cataracts | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.199 | OCRL | Sarah Leigh Phenotypes for gene: OCRL were changed from Lowe syndrome (Disorders of amino acid transport); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Intellectual disability; Intellectual_disability; Cataracts to Dent disease 2 300555; Lowe syndrome 309000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.198 | OCRL | Sarah Leigh Phenotypes for gene: OCRL were changed from Lowe syndrome (Disorders of amino acid transport); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Intellectual disability; Intellectual_disability; Cataracts to Lowe syndrome (Disorders of amino acid transport); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Intellectual disability; Intellectual_disability; Cataracts | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.196 | OCRL | Sarah Leigh Phenotypes for gene: OCRL were changed from Lowe syndrome (Disorders of amino acid transport); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Intellectual disability; Intellectual_disability; Cataracts to Lowe syndrome (Disorders of amino acid transport); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Intellectual disability; Intellectual_disability; Cataracts | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.195 | NDUFB9 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 1 variant reported, together with supportive functional studies. |
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| Likely inborn error of metabolism - targeted testing not possible v1.193 | NDUFB9 | Sarah Leigh Added comment: Comment on publications: PMID: 22200994 Reports one probound heterozygous for a variant (c.140G>T, p.Arg47Leu) within NDUFB9 with parents not available for genetic testing, and in vitro complement studies in patient fibroblasts showed wildtype NDUFB9 did not rescue complex I activity, therefore was deemed not pathogenic. Reports two brothers homozygous for a variant in the gene, with parents who are heterozygous carriers (c.191T>C, p.Leu64Pro). In vitro, fibroblasts from the proband showed low complex I activity, and wildtype NDUFB9 rescued complex I activity. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.193 | NDUFB9 | Sarah Leigh Publications for gene: NDUFB9 were set to PMID: 22200994 Reports one probound heterozygous for a variant (c.140G>T, p.Arg47Leu) within NDUFB9 with parents not available for genetic testing, and in vitro complement studies in patient fibroblasts showed wildtype NDUFB9 did not rescue complex I activity, therefore was deemed not pathogenic. Reports two brothers homozygous for a variant in the gene, with parents who are heterozygous carriers (c.191T>C, p.Leu64Pro). In vitro, fibroblasts from the proband showed low complex I activity, and wildtype NDUFB9 rescued complex I activity. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.190 | MVK | Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 8 variants reported in Hyper-IgD syndrome 260920, 9 variants reported in Mevalonic aciduria 610377 and 8 variants reported in Porokeratosis 3, multiple types 175900. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.189 | MVK | Sarah Leigh Phenotypes for gene: MVK were changed from Infantile enterocolitis & monogenic inflammatory bowel disease; Mevalonate kinase deficiency (Disorders of sterol biosynthesis) to Hyper-IgD syndrome 260920; Mevalonic aciduria 610377; Porokeratosis 3, multiple types 175900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.184 | MOCS2 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 9 variants reported in at least 8 unrelated cases, together with supportive functional studies. |
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| Likely inborn error of metabolism - targeted testing not possible v1.180 | MOCS1 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 5 variants reported unrelated cases. |
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| Likely inborn error of metabolism - targeted testing not possible v1.176 | MAOA |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 variants reported in unrelated cases. |
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| Likely inborn error of metabolism - targeted testing not possible v1.176 | MAOA |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 variants reported in unrelated cases. |
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| Likely inborn error of metabolism - targeted testing not possible v1.175 | MAGT1 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 3 variants reported in unrelated cases, together with mouse knock-out model (PMID 29581357). |
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| Likely inborn error of metabolism - targeted testing not possible v1.169 | LIPC |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in two unrelated families with Hepatic lipase deficiency, 614025. |
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| Likely inborn error of metabolism - targeted testing not possible v1.167 | LDLRAP1 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 11 variants reported. |
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| Likely inborn error of metabolism - targeted testing not possible v1.162 | LDLR |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Over 2000 variants reported. |
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| Likely inborn error of metabolism - targeted testing not possible v1.160 | LBR |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for Greenberg skeletal dysplasia 215140. At least 15 variants have been reported, in 5 unrelated cases of Pelger-Huet anomaly 169400, 3 unrelated cases of Pelger-Huet anomaly with mild skeletal anomalies 618019, 5 unrelated cases of Greenberg skeletal dysplasia 215140 and in a single case of ?Reynolds syndrome 613471. |
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| Likely inborn error of metabolism - targeted testing not possible v1.156 | HSD17B10 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for 2-methyl-3-hydroxybutyrylL-coA dehydrogenase deficiency and for mental retardation syndromic X-linked type 10 . At least 8 variants reported. |
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| Likely inborn error of metabolism - targeted testing not possible v1.151 | HPS1 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in at least 5 unrelated cases. |
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| Likely inborn error of metabolism - targeted testing not possible v1.149 | HPD |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for both phenotypes. At least 4 variants reported in unrelated cases of Tyrosinemia, type III 276710 and 4 variants in 6 unrelated cases of Hawkinsinuria 140350 (at least 2 of these cases were compound heterozygotes). |
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| Likely inborn error of metabolism - targeted testing not possible v1.146 | HADH |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. Numerous variants reported in unrelated cases of Hyperinsulinemic hypoglycemia, familial, 4 609975. |
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| Likely inborn error of metabolism - targeted testing not possible v1.143 | GNMT |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in 2 unrelated cases, with supportive functional data. |
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| Likely inborn error of metabolism - targeted testing not possible v1.142 | GNMT |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in 2 unrelated cases, with supportive functional data. |
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| Likely inborn error of metabolism - targeted testing not possible v1.142 | GNMT |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in 2 unrelated cases, with supportive functional data. |
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| Likely inborn error of metabolism - targeted testing not possible v1.140 | GLUL |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 3 variants reported in unrelated cases. |
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| Likely inborn error of metabolism - targeted testing not possible v1.135 | GK |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 8 variants reported. |
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| Likely inborn error of metabolism - targeted testing not possible v1.131 | GAMT |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 5 variants reported in 4 unrelated cases. |
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| Likely inborn error of metabolism - targeted testing not possible v1.128 | FTCD |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 15 variants reported. |
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| Likely inborn error of metabolism - targeted testing not possible v1.124 | FGFR2 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with 14 phenotypes in OMIM and as confirmed Gen2Phen gene for acrocephalosyndactyly type V, Antley-Bixler syndrome, Apert syndrome, Beare-Stevenson cutis gyrata syndrome, Crouzon syndrome, familial scaphocephaly syndrome, Jackson-Weiss syndrome, lacrimo-auriculo-dento-digital syndrome. At least 44 variants reported. |
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| Likely inborn error of metabolism - targeted testing not possible v1.119 | FECH | Sarah Leigh Phenotypes for gene: FECH were changed from Protoporphyria, erythropoietic, 1 177000 to Protoporphyria, erythropoietic, 1 177000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.119 | FECH | Sarah Leigh Phenotypes for gene: FECH were changed from Erythropoietic protoporphyria, mild variant; Erythropoietic protoporphyria (Porphyrias with acute painful photosensitivity) to Protoporphyria, erythropoietic, 1 177000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.118 | DPM3 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported as homozygotes in two unrelated cases, together with segregation and supportive functional studies. |
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| Likely inborn error of metabolism - targeted testing not possible v1.115 | DHDDS |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for Retinitis pigmentosa 59 613861. One variant was reported in at least 15 families with retinitis pigmentosa, but only one compound individual with glycosylation defects was identifed so far (PMID 27343064). |
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| Likely inborn error of metabolism - targeted testing not possible v1.113 | DHODH |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 11 variants reported in 6 families (PMID 19915526), together with a knockout mouse model (PMID 27626380). |
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| Likely inborn error of metabolism - targeted testing not possible v1.109 | DHCR24 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in at least cases, two of the variants were in cis in a case which was compound heterozygous with another variant (PMID 11519011). Supportive functional studies were also presented. |
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| Likely inborn error of metabolism - targeted testing not possible v1.109 | DHCR24 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in at least cases, two of the variants were in cis in a case which was compound heterozygous with another variant (PMID 11519011). Supportive functional studies were also presented. |
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| Likely inborn error of metabolism - targeted testing not possible v1.93 | CLDN19 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 5 variants reported in at least 6 unrelated cases. |
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| Likely inborn error of metabolism - targeted testing not possible v1.90 | CISD2 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as both RD and IF Gen2Phen gene. At least 3 variants reported in unrelated cases, together with segration and functional studies. |
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| Likely inborn error of metabolism - targeted testing not possible v1.87 | ASAH1 | Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in 6 cases of Farber lipogranulomatosis 228000 and 5 variants in 3 cases of Spinal muscular atrophy with progressive myoclonic epilepsy 159950.; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in 6 cases of Farber lipogranulomatosis 228000 and 5 variants in 3 cases of Spinal muscular atrophy with progressive myoclonic epilepsy 159950. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.85 | ALPL |
Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 16 variants reported in hypophosphatasia, infantile 241500, some of these variants and others were found in childhood and adult Hypophosphatasia and two addtional variants were reported in a case of perinatal lethal hypophosphatasia (PMID 11745997).; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 16 variants reported in hypophosphatasia, infantile 241500, some of these variants and others were found in childhood and adult Hypophosphatasia and two addtional variants were reported in a case of perinatal lethal hypophosphatasia (PMID 11745997). |
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| Likely inborn error of metabolism - targeted testing not possible v1.85 | ALG13 |
Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported, one of which (c.320A>G, p.N107S) is associated with Epileptic encephalopathy, early infantile, 36 300884 as a de novo variant in at least 6 unrelated cases, athough the conection with Congenital disorder of glycosylation, type Is 300884 is not clear from these cases. The second variant was reported in an infant who died at age 1 year. Transferrin isoelectric focusing showed abnormal N-glycosylation and was consistent with a diagnostic classification of congenital disorder of glycosylation type Is (CDG1S). Studies of patient-derived cells showed decreased enzyme activity, at about 17% of wildtype (PMID 22492991).; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported, one of which (c.320A>G, p.N107S) is associated with Epileptic encephalopathy, early infantile, 36 300884 as a de novo variant in at least 6 unrelated cases, athough the conection with Congenital disorder of glycosylation, type Is 300884 is not clear from these cases. The second variant was reported in an infant who died at age 1 year. Transferrin isoelectric focusing showed abnormal N-glycosylation and was consistent with a diagnostic classification of congenital disorder of glycosylation type Is (CDG1S). Studies of patient-derived cells showed decreased enzyme activity, at about 17% of wildtype (PMID 22492991). |
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| Likely inborn error of metabolism - targeted testing not possible v1.83 | ALPL | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 16 variants reported in hypophosphatasia, infantile 241500, some of these variants and others were found in childhood and adult Hypophosphatasia and two addtional variants were reported in a case of perinatal lethal hypophosphatasia (PMID 11745997). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.81 | ALG13 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported, one of which (c.320A>G, p.N107S) is associated with Epileptic encephalopathy, early infantile, 36 300884 as a de novo variant in at least 6 unrelated cases, athough the conection with Congenital disorder of glycosylation, type Is 300884 is not clear from these cases. The second variant was reported in an infant who died at age 1 year. Transferrin isoelectric focusing showed abnormal N-glycosylation and was consistent with a diagnostic classification of congenital disorder of glycosylation type Is (CDG1S). Studies of patient-derived cells showed decreased enzyme activity, at about 17% of wildtype (PMID 22492991). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.79 | ISCU | Sarah Leigh Added comment: Comment on mode of inheritance: PMID 29079705 reports a novel de novo dominant variant in ISCU associated with mitochondrial myopathy, which justifies the mode of inheritance recorded here. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.78 | 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). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.78 | 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). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.71 | RANBP2 | Sarah Leigh Added comment: Comment on list classification: Demoted RANBP2 from Green to Amber following review by Zornitza Stark and agreement from Helen Brittain (Genomics England clinical team). Recent papers report patients with symptoms (including seizures) after a viral illness (PMID:30796099, PMID:28336122, PMID:25128471). However, listed as a susceptibility locus in OMIM, and papers report incomplete penetrance: variant present in asymptomatic maternal grandmother in PMID:30796099 and in the father in PMID:28336122. Therefore further information (e.g. on penetrance) is required for a clear gene:disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.66 | MANBA | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 9 variants reported in 6 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.62 | ASAH1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in 6 cases of Farber lipogranulomatosis 228000 and 5 variants in 3 cases of Spinal muscular atrophy with progressive myoclonic epilepsy 159950. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.62 | ASAH1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in 6 cases of Farber lipogranulomatosis 228000 and 5 variants in 3 cases of Spinal muscular atrophy with progressive myoclonic epilepsy 159950. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.61 | DHCR7 |
Sarah Leigh changed review comment from: Comment on list classification: Associated with phenotype in OMIM and as confirmed Gen2Phen gene. At least 21 variants reported.; to: Comment on list classification: Associated with phenotype in OMIM and as confirmed Gen2Phen gene. At least 21 variants reported. Although single gene testing has been commissioned for DHCR7, it is well established as an inherited metabolic disorder and ought to be included in the overall panel in case it has not been biochemically excluded initially Saikat Santra (Birmingham Children's Hospital), 21 Dec 2018 |
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| Likely inborn error of metabolism - targeted testing not possible v1.61 | DHCR7 | Sarah Leigh Added comment: Comment on list classification: Associated with phenotype in OMIM and as confirmed Gen2Phen gene. At least 21 variants reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.55 | UQCRQ | Sarah Leigh Added comment: Comment on list classification: Amber review collated by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: One variant reported in a consanguineous Israeli Bedouin kindred with Mitochondrial complex III deficiency, nuclear type 4 (615159)(PMID: 18439546). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.53 | NDUFA1 | Ellen McDonagh Added comment: Comment on mode of inheritance: Changed from 'Both monoallelic and biallelic' to X-linked, as encoded on the X-chromosome. One study reports a female with a heterozygous variant who developed a very mild form of complex I deficiency due to skewed X inactivation [PMID: 21596602]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.50 | MRPL44 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green on the Mitochondrial disorders (Version 1.138) gene panel due to to reports in 3 unrelated cases/families, therefore promoting this gene in this panel to reflect this change in rating. See publications for evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v1.47 | POR |
Ivone Leong Source NHS GMS was added to POR. Source London North GLH was added to POR. |
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| Likely inborn error of metabolism - targeted testing not possible v1.43 | SLC25A4 | Rebecca Foulger Phenotypes for gene: SLC25A4 were changed from Progressive External Ophthalmoplegia with Mitochondrial DNADeletions; Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity; Disorders of mitochondrial protein transport; Progressive external ophthalmoplegia with mitochondrial DNA deletions 3, 609283Mitochondrial DNA depletion syndrome 12 (cardiomyopathic type), 615418 to Progressive External Ophthalmoplegia with Mitochondrial DNADeletions; Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity; Disorders of mitochondrial protein transport; Progressive external ophthalmoplegia with mitochondrial DNA deletions 3, 609283; Mitochondrial DNA depletion syndrome 12 (cardiomyopathic type), 615418 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v0.25 | GLUD1 | Ellen McDonagh Added comment: Comment on mode of pathogenicity: Mutation consequence summary from G2P = activating. OMIM reports several missense variants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v0.18 | TIMM50 |
Sarah Leigh gene: TIMM50 was added gene: TIMM50 was added to Inborn errors of metabolism. Sources: Expert Review,Literature Mode of inheritance for gene: TIMM50 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TIMM50 were set to 27573165 Phenotypes for gene: TIMM50 were set to 3-methylglutaconic aciduria, type IX 617698 Review for gene: TIMM50 was set to AMBER Added comment: Associated with phenotype in OMIM and not in Gen2Phen. At least 2 variants identified in 2 unrelated cases in peer reviewed literature. An additional biallelic variant has been reported in a case with intractable epilepsy and developmental delay accompanied by 3-methylglutaconic aciduria a meeting abstract. (Three unrelated families reported with bi-allelic variants in this gene. Zornitza Stark (Australian Genomics), 1 Sep 2018) Sources: Expert Review, Literature |
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| Likely inborn error of metabolism - targeted testing not possible v0.16 | MRPS34 |
Sarah Leigh gene: MRPS34 was added gene: MRPS34 was added to Inborn errors of metabolism. Sources: Expert Review,Literature Mode of inheritance for gene: MRPS34 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MRPS34 were set to 28777931 Phenotypes for gene: MRPS34 were set to Combined oxidative phosphorylation deficiency 32 617664 Review for gene: MRPS34 was set to GREEN Added comment: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 4 variants reported in 3 unrelated cases. (Six individuals from four unrelated families reported in the literature with bi-allelic variants in this gene. Zornitza Stark (Australian Genomics), 30 Aug 2018) Sources: Expert Review, Literature |
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| Likely inborn error of metabolism - targeted testing not possible v0.12 | C1QBP |
Sarah Leigh gene: C1QBP was added gene: C1QBP was added to Inborn errors of metabolism. Sources: Literature,Expert Review Mode of inheritance for gene: C1QBP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C1QBP were set to 28942965 Phenotypes for gene: C1QBP were set to Combined oxidative phosphorylation deficiency 33 617713 Review for gene: C1QBP was set to GREEN Added comment: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 4 variants reported 4 unrelated cases. Sources: Literature, Expert Review |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | TRAP1 |
Ellen McDonagh gene: TRAP1 was added gene: TRAP1 was added to Inborn errors of metabolism. Sources: Expert Review Red Mode of inheritance for gene: TRAP1 was set to Unknown Publications for gene: TRAP1 were set to PMID: 24152966 - recessive mutations reported in 2 families with CAKUT, and 3 families with VACTERL. |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | ALAS2 |
Ellen McDonagh gene: ALAS2 was added gene: ALAS2 was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: ALAS2 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: ALAS2 were set to 27604308 Phenotypes for gene: ALAS2 were set to Erythropoietic protoporphyria, mild variant; X-linked sideroblastic anaemia (XLSA) (Porphyrias with acute painful photosensitivity); X-linked dominant protoporphyria (Porphyrias with acute painful photosensitivity) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | TIMM8A |
Ellen McDonagh Added phenotypes Mohr-Tranebjaerg syndrome, 304700; Jensen syndrome, 311150; Disorders of the mitochondrial import system; Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Deafness, X-linked 1, progressive for gene: TIMM8A Publications for gene TIMM8A were changed from to 27604308 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | TIMM8A |
Ellen McDonagh gene: TIMM8A was added gene: TIMM8A was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: TIMM8A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: TIMM8A were set to Mohr-Tranebjaerg syndrome, 304700; Jensen syndrome, 311150; Disorders of the mitochondrial import system; Deafness, X-linked 1, progressive |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC6A8 |
Ellen McDonagh gene: SLC6A8 was added gene: SLC6A8 was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: SLC6A8 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: SLC6A8 were set to 27604308 Phenotypes for gene: SLC6A8 were set to Intellectual disability; Creatine transporter deficiency (Mitochondrial respiratory chain disorders (caused by nuclear variants only), disorders of creatinine metabolism) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | OCRL |
Ellen McDonagh gene: OCRL was added gene: OCRL was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: OCRL was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: OCRL were set to 27604308 Phenotypes for gene: OCRL were set to Lowe syndrome (Disorders of amino acid transport); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Intellectual disability; Intellectual_disability; Cataracts |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | TARS2 |
Ellen McDonagh gene: TARS2 was added gene: TARS2 was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: TARS2 was set to Unknown Publications for gene: TARS2 were set to PMID: 24827421 - Compound heterozygous variants in TARS2 were reported in the proband and his affected sister - a missense mutation (c.845C>T, p.Pro282Leu) and a nucleotide change in position +3 of intron 6 (g.4255A>G, c.695+3A>G). The parents carrying one of the variants, one unaffected sister carried one variant, and the other unaffected sibling carried neither. Phenotypes for gene: TARS2 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); ?Combined oxidative phosphorylation deficiency 21, 615918 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC25A2 |
Ellen McDonagh gene: SLC25A2 was added gene: SLC25A2 was added to Inborn errors of metabolism. Sources: Expert Review Red Mode of inheritance for gene: SLC25A2 was set to Unknown Publications for gene: SLC25A2 were set to 27604308 Phenotypes for gene: SLC25A2 were set to Riboflavin transporter deficiency (Disorders of riboflavin transport and metabolism) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | HMBS |
Ellen McDonagh gene: HMBS was added gene: HMBS was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: HMBS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HMBS were set to 27604308 Phenotypes for gene: HMBS were set to Porphyria, acute intermittent, nonerythroid variant, 176000; Acute intermittent porphyria (Acute neuropathic porphyrias); Porphyria, acute intermittent, 176000 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | CHCHD10 | Ellen McDonagh Added phenotypes Frontotemporal dementia and/or amyotrophic lateral sclerosis 2; ?Myopathy, isolated mitochondrial, autosomal dominant, 616209; Spinal muscular atrophy, Jokela type for gene: CHCHD10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v0.4 | CHCHD10 |
Ellen McDonagh gene: CHCHD10 was added gene: CHCHD10 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: CHCHD10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: CHCHD10 were set to Frontotemporal dementia and/or amyotrophic lateral sclerosis 2; ?Myopathy, isolated mitochondrial, autosomal dominant, 616209; Spinal muscular atrophy, Jokela type |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | UROD |
Ellen McDonagh gene: UROD was added gene: UROD was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: UROD was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: UROD were set to 27604308 Phenotypes for gene: UROD were set to Porphyria cutanea tarda (Porphyrias with erosive photodermatosis) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC25A4 | Ellen McDonagh Added phenotypes Progressive External Ophthalmoplegia with Mitochondrial DNADeletions; Disorders of mitochondrial DNA maintenance and integrity; Disorders of mitochondrial protein transport; Progressive external ophthalmoplegia with mitochondrial DNA deletions 3, 609283Mitochondrial DNA depletion syndrome 12 (cardiomyopathic type), 615418 for gene: SLC25A4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC25A4 |
Ellen McDonagh gene: SLC25A4 was added gene: SLC25A4 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: SLC25A4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SLC25A4 were set to 27604308 Phenotypes for gene: SLC25A4 were set to Progressive External Ophthalmoplegia with Mitochondrial DNADeletions; Disorders of mitochondrial protein transport; Disorders of mitochondrial DNA maintenance and integrity; Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Progressive external ophthalmoplegia with mitochondrial DNA deletions 3, 609283Mitochondrial DNA depletion syndrome 12 (cardiomyopathic type), 615418 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC2A1 |
Ellen McDonagh gene: SLC2A1 was added gene: SLC2A1 was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: SLC2A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SLC2A1 were set to 27604308 Phenotypes for gene: SLC2A1 were set to Intellectual disability; Early onset dystonia; Cataracts; Glucose transporter 1 deficiency (blood-brain barrier) (Disorders of glucose transport); Hereditary ataxia; Epileptic encephalopathy; Familial Genetic Generalised Epilepsies |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | PPOX |
Ellen McDonagh gene: PPOX was added gene: PPOX was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: PPOX was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: PPOX were set to 27604308; 19460837; 9811936 Phenotypes for gene: PPOX were set to Porphyria variegata 176200; Variegate porphyria (Acute neuropathic porphyrias) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | CPOX |
Ellen McDonagh gene: CPOX was added gene: CPOX was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: CPOX was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: CPOX were set to 27604308 Phenotypes for gene: CPOX were set to Harderoporphyria 121300; Coproporphyria 121300; Hereditary coproporphyria (Acute neuropathic porphyrias) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | ATP8B1 |
Ellen McDonagh gene: ATP8B1 was added gene: ATP8B1 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: ATP8B1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ATP8B1 were set to 27604308 Phenotypes for gene: ATP8B1 were set to Cholestasis, progressive familial intrahepatic 1 211600; Cholestasis, benign recurrent intrahepatic 243300 AR; Cholestasis, intrahepatic, of pregnancy, 1 147480 AD; Byler disease (Disorders of bile acid metabolism and transport) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | ABCB4 |
Ellen McDonagh gene: ABCB4 was added gene: ABCB4 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: ABCB4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ABCB4 were set to 27604308 Phenotypes for gene: ABCB4 were set to Gallbladder disease 1 600803 AD, AR; Cholestasis, progressive familial intrahepatic 3 602347 AR; Progressive familial intrahepatic cholestasis type 3 (Disorders of bile acid metabolism and transport); Cholestasis, intrahepatic, of pregnancy, 3 614972 AD, AR |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC7A9 |
Ellen McDonagh gene: SLC7A9 was added gene: SLC7A9 was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: SLC7A9 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: SLC7A9 were set to 27604308; 24816252 Phenotypes for gene: SLC7A9 were set to Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Cystinuria (Disorders of amino acid transport) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC3A1 |
Ellen McDonagh gene: SLC3A1 was added gene: SLC3A1 was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: SLC3A1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: SLC3A1 were set to 27604308 Phenotypes for gene: SLC3A1 were set to Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Cystinuria (Disorders of amino acid transport); Hypotonia-cystinuria syndrome (Disorders of amino acid transport) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | UROS |
Ellen McDonagh gene: UROS was added gene: UROS was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: UROS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UROS were set to 27604308 Phenotypes for gene: UROS were set to Congenital erythropoietic porphyria (Porphyrias with erosive photodermatosis); Porphyria, congenital erythropoietic 263700 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | UQCRB |
Ellen McDonagh Added phenotypes Mitochondrial complex III deficiency, nuclear type 3 615158; Complex III (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits) for gene: UQCRB Publications for gene UQCRB were changed from PMID: 12709789 (case report); PMID: 23454382 (functional study); PMID: 25446085 (functional study) to 27604308 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | UQCRB |
Ellen McDonagh gene: UQCRB was added gene: UQCRB was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: UQCRB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UQCRB were set to PMID: 12709789 (case report); PMID: 23454382 (functional study); PMID: 25446085 (functional study) Phenotypes for gene: UQCRB were set to Mitochondrial Diseases; Mitochondrial complex III deficiency, nuclear type 3, 615158; Isolated complex III deficiency |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | UGT1A1 |
Ellen McDonagh gene: UGT1A1 was added gene: UGT1A1 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: UGT1A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UGT1A1 were set to 27604308; 24816252 Phenotypes for gene: UGT1A1 were set to Crigler-Najjar syndrome, type I 218800; Bilirubin UDP-glucuronosyltransferase 1 deficiency (Disorders of bile acid metabolism and transport); Crigler-Najjar syndrome, type II 606785 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | TCN2 |
Ellen McDonagh gene: TCN2 was added gene: TCN2 was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: TCN2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TCN2 were set to 27604308 Phenotypes for gene: TCN2 were set to Congenital neutropaenia; Intellectual disability; A- or hypo-gammaglobulinaemia; Agranulocytosis; Combined B and T cell defect; SCID; Transcobalamin II deficiency (Disorders of cobalamin absorption, transport and metabolism) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | TCN1 |
Ellen McDonagh gene: TCN1 was added gene: TCN1 was added to Inborn errors of metabolism. Sources: Expert Review Red Mode of inheritance for gene: TCN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TCN1 were set to 27604308 Phenotypes for gene: TCN1 were set to Haptocorrin deficiency (Disorders of cobalamin absorption, transport and metabolism); No OMIM number |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC7A7 |
Ellen McDonagh gene: SLC7A7 was added gene: SLC7A7 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: SLC7A7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC7A7 were set to 27604308 Phenotypes for gene: SLC7A7 were set to Lysinuric protein intolerance (Disorders of amino acid transport); Lysinuric protein intolerance 222700 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC6A3 |
Ellen McDonagh gene: SLC6A3 was added gene: SLC6A3 was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: SLC6A3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC6A3 were set to 27604308 Phenotypes for gene: SLC6A3 were set to Intellectual disability; Early onset dystonia; Dopamine transporter deficiency syndrome (Other disorders of neurotransmitter metabolism); Parkinson Disease and Complex Parkinsonism |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC5A1 |
Ellen McDonagh gene: SLC5A1 was added gene: SLC5A1 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: SLC5A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC5A1 were set to 27604308 Phenotypes for gene: SLC5A1 were set to Glucose/galactose malabsorption (Disorders of glucose transport); Glucose/galactose malabsorption 606824 (Disorders of glucose transport) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC46A1 |
Ellen McDonagh gene: SLC46A1 was added gene: SLC46A1 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: SLC46A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC46A1 were set to 27604308 Phenotypes for gene: SLC46A1 were set to Folate malabsorption, hereditary; Hereditary folate malabsorption (Disorders of folate metabolism and transport) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC35C1 |
Ellen McDonagh Added phenotypes Congenital disorder of glycosylation, type IIc 266265; GDP-fucose transporter deficiency (Disorders of multiple glycosylation and other glycosylation pathways) for gene: SLC35C1 Publications for gene SLC35C1 were changed from 27604308 to 12476046; 11326280 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC35C1 |
Ellen McDonagh gene: SLC35C1 was added gene: SLC35C1 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: SLC35C1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC35C1 were set to 27604308 Phenotypes for gene: SLC35C1 were set to GDP-fucose transporter deficiency (Disorders of multiple glycosylation and other glycosylation pathways); Congenital disorder of glycosylation, type IIc 266265 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC35A1 |
Ellen McDonagh Added phenotypes Congenital disorder of glycosylation, type Iif, 603585; CMP-sialic acid transporter deficiency (Disorders of multiple glycosylation and other glycosylation pathways) for gene: SLC35A1 Publications for gene SLC35A1 were changed from 23873973; 15576474 to 27604308 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC35A1 |
Ellen McDonagh gene: SLC35A1 was added gene: SLC35A1 was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: SLC35A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC35A1 were set to 23873973; 15576474 Phenotypes for gene: SLC35A1 were set to Congenital disorder of glycosylation, type IIf 603585; CMP-sialic acid transporter deficiency (Disorders of multiple glycosylation and other glycosylation pathways) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC2A2 |
Ellen McDonagh gene: SLC2A2 was added gene: SLC2A2 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: SLC2A2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC2A2 were set to 27604308 Phenotypes for gene: SLC2A2 were set to Glycogen storage disease type XI (Glycogen storage disorders); Glycogen Storage Disorders- Liver; Glucose transporter 2 deficiency (Disorders of glucose transport); Fanconi-Bickel Syndrome; renal falcon syndrome, aminoaciduria phosphaturia, small stature, malabsorption, hepatomegaly and nephromegaly. |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC25A38 |
Ellen McDonagh gene: SLC25A38 was added gene: SLC25A38 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: SLC25A38 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC25A38 were set to 27604308 Phenotypes for gene: SLC25A38 were set to severe, non-syndromic, microcytic/hypochromic sideroblastic anemia; nonsyndromic autosomal recessive congenital sideroblastic anemia; Disorders of mitochondrial solute import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); congenital sideroblastic anemias |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC25A3 |
Ellen McDonagh Added phenotypes Mitochondrial phosphate carrier deficiency 610773; Disorders of mitochondrial solute import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Riboflavin transporter deficiency (Disorders of riboflavin transport and metabolism) for gene: SLC25A3 Publications for gene SLC25A3 were changed from 27604308; 17273968; 25681081 to 27604308 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC25A22 |
Ellen McDonagh Added phenotypes Epileptic encephalopathy, early infantile, 3, 609304; Disorders of mitochondrial solute import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: SLC25A22 Publications for gene SLC25A22 were changed from to 27604308 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC25A20 |
Ellen McDonagh gene: SLC25A20 was added gene: SLC25A20 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: SLC25A20 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC25A20 were set to 27604308 Phenotypes for gene: SLC25A20 were set to Carnitine-acylcarnitine translocase deficiency 212138; Carnitine acylcarnitine translocase deficiency (Disorders of carnitine transport and the carnitine cycle) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC25A12 |
Ellen McDonagh gene: SLC25A12 was added gene: SLC25A12 was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: SLC25A12 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC25A12 were set to 27604308 Phenotypes for gene: SLC25A12 were set to Disorders of mitochondrial solute import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Inherited white matter disorders |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC25A1 | Ellen McDonagh Added phenotypes Combined D-2- and L-2-hydroxyglutaric aciduria, 615182; Disorders of mitochondrial protein transport for gene: SLC25A1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC25A1 |
Ellen McDonagh gene: SLC25A1 was added gene: SLC25A1 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: SLC25A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC25A1 were set to 27604308 Phenotypes for gene: SLC25A1 were set to Combined D-2- and L-2-hydroxyglutaric aciduria, 615182; Riboflavin transporter deficiency (Disorders of riboflavin transport and metabolism) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC22A5 |
Ellen McDonagh gene: SLC22A5 was added gene: SLC22A5 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: SLC22A5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC22A5 were set to 27604308; 24816252 Phenotypes for gene: SLC22A5 were set to Propionicacidemia; Carnitine transporter deficiency (Disorders of carnitine transport and the carnitine cycle) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | SLC18A2 |
Ellen McDonagh gene: SLC18A2 was added gene: SLC18A2 was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: SLC18A2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC18A2 were set to 27604308; 26497564; 23363473 Phenotypes for gene: SLC18A2 were set to Brain Dopamine Serotonin Vesicular Transport Disease (Other disorders of neurotransmitter metabolism); Brain Dopamine Serotonin Vesicular Transport Disease (Other disorders of neurotransmitter metabolism) (NO phenotype number in OMIM) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | PREPL |
Ellen McDonagh gene: PREPL was added gene: PREPL was added to Inborn errors of metabolism. Sources: Expert Review Red Mode of inheritance for gene: PREPL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PREPL were set to 27604308 Phenotypes for gene: PREPL were set to Hypotonia-cystinuria syndrome 606407; Hypotonia-cystinuria syndrome (Disorders of amino acid transport) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | POR |
Ellen McDonagh gene: POR was added gene: POR was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: POR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POR were set to 27604308 Phenotypes for gene: POR were set to Antley-Bixler syndrome with disordered steroidogenesis; Unexplained skeletal dysplasia; Disorders of sex development; Craniosynostosis syndromes phenotypes |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | PNPT1 |
Ellen McDonagh Added phenotypes Deafness, autosomal recessive 70, 614934; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 13, 614932; respiratory chain disorder; hearing loss; Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: PNPT1 Publications for gene PNPT1 were changed from to 27604308 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | PDSS1 |
Ellen McDonagh Added phenotypes Coenzyme Q10 deficiency, primary, 2, 614651; Disorders of CoQ10 biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of ubiquinone metabolism and biosynthesis for gene: PDSS1 Publications for gene PDSS1 were changed from PMID: 22494076 (2012) - A girl with developmental delay, nephrotic syndrome, and failure to thrive was reported to be a compound heterozygote for two novel variants in PDSS1 (p.Arg221Term and p.Ser370Arg).; PMID: 17332895 (2007) - Report a homozygous nucleotide substitution modifying a conserved amino acid of the protein (D308E) in a consanguineous family with CoQ10 deficiency to 27604308 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | PDSS1 |
Ellen McDonagh gene: PDSS1 was added gene: PDSS1 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: PDSS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDSS1 were set to PMID: 22494076 (2012) - A girl with developmental delay, nephrotic syndrome, and failure to thrive was reported to be a compound heterozygote for two novel variants in PDSS1 (p.Arg221Term and p.Ser370Arg).; PMID: 17332895 (2007) - Report a homozygous nucleotide substitution modifying a conserved amino acid of the protein (D308E) in a consanguineous family with CoQ10 deficiency Phenotypes for gene: PDSS1 were set to Coenzyme Q10 deficiency, primary, 2, 614651; Disorders of ubiquinone metabolism and biosynthesis |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | NDUFB9 |
Ellen McDonagh Added phenotypes ?Mitochondrial complex I deficiency, 252010; Isolated complex I deficiency for gene: NDUFB9 Publications for gene NDUFB9 were changed from 27604308 to PMID: 22200994 Reports one probound heterozygous for a variant (c.140G>T, p.Arg47Leu) within NDUFB9 with parents not available for genetic testing, and in vitro complement studies in patient fibroblasts showed wildtype NDUFB9 did not rescue complex I activity, therefore was deemed not pathogenic. Reports two brothers homozygous for a variant in the gene, with parents who are heterozygous carriers (c.191T>C, p.Leu64Pro). In vitro, fibroblasts from the proband showed low complex I activity, and wildtype NDUFB9 rescued complex I activity. |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | MTHFR |
Ellen McDonagh gene: MTHFR was added gene: MTHFR was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: MTHFR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MTHFR were set to 27604308 Phenotypes for gene: MTHFR were set to Methylenetetrahydrofolate reductase deficiency (Disorders of folate metabolism and transport); Homocystinuria due to MTHFR deficiency |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | MMAB |
Ellen McDonagh gene: MMAB was added gene: MMAB was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: MMAB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MMAB were set to 27604308 Phenotypes for gene: MMAB were set to Defect in adenosylcobalamin synthesis-cbl B (Disorders of cobalamin absorption, transport and metabolism); Methylmalonic aciduria, vitamin B12-responsive, due to defect in synthesis of adenosylcobalamin, cblB complementation type 251110 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | MMAA |
Ellen McDonagh gene: MMAA was added gene: MMAA was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: MMAA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MMAA were set to 27604308 Phenotypes for gene: MMAA were set to Methylmalonic aciduria, vitamin B12-responsive 251100; Defect in adenosylcobalamin synthesis-cbl A (Disorders of cobalamin absorption, transport and metabolism) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | GFER |
Ellen McDonagh Added phenotypes Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay,613076; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Disorders of the mitochondrial import system; Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: GFER Publications for gene GFER were changed from 19409522; PMID: 26018198 to 27604308 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | GFER |
Ellen McDonagh gene: GFER was added gene: GFER was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: GFER was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GFER were set to 19409522; PMID: 26018198 Phenotypes for gene: GFER were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Disorders of the mitochondrial import system; Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay,613076 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | FOLR1 |
Ellen McDonagh gene: FOLR1 was added gene: FOLR1 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: FOLR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FOLR1 were set to 27604308 Phenotypes for gene: FOLR1 were set to Neurodegeneration due to cerebral folate transport deficiency, 613068; Cerebral folate deficiency due to FOLR1 deficiency (Disorders of folate metabolism and transport) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | FECH |
Ellen McDonagh gene: FECH was added gene: FECH was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: FECH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FECH were set to 27604308 Phenotypes for gene: FECH were set to Erythropoietic protoporphyria, mild variant; Erythropoietic protoporphyria (Porphyrias with acute painful photosensitivity) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | DNAJC19 |
Ellen McDonagh gene: DNAJC19 was added gene: DNAJC19 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: DNAJC19 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNAJC19 were set to 16055927; 27604308; 27426421; 22797137; 27928778 Phenotypes for gene: DNAJC19 were set to 3-methylglutaconic aciduria, type V, 610198; Disorders of the mitochondrial import system |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | DHFR |
Ellen McDonagh gene: DHFR was added gene: DHFR was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: DHFR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DHFR were set to 27604308 Phenotypes for gene: DHFR were set to Dihydrofolate reductase deficiency (Disorders of folate metabolism and transport); Megaloblastic anemia due to dihydrofolate reductase deficiency |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | CUBN |
Ellen McDonagh gene: CUBN was added gene: CUBN was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: CUBN was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CUBN were set to Intrinsic factor receptor deficiency due to CUBN mutations (Disorders of cobalamin absorption, transport and metabolism); Megaloblastic anemia-1, Finnish type; Proteinuric renal disease; Unexplained kidney failure in young people |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | CPT2 |
Ellen McDonagh gene: CPT2 was added gene: CPT2 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: CPT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CPT2 were set to 27604308; 24816252 Phenotypes for gene: CPT2 were set to CPT deficiency, hepatic, type II 600649; CPT II deficiency, lethal neonatal 608836; Carnitine palmitoyltransferase II (CPTII) deficiency (Disorders of carnitine transport and the carnitine cycle) |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | CPT1A |
Ellen McDonagh gene: CPT1A was added gene: CPT1A was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: CPT1A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CPT1A were set to 27604308 Phenotypes for gene: CPT1A were set to Carnitine palmitoyltransferase I (CPTI) deficiency (Disorders of carnitine transport and the carnitine cycle); CPT deficiency, hepatic, type IA |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | AMN |
Ellen McDonagh gene: AMN was added gene: AMN was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: AMN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AMN were set to 27604308 Phenotypes for gene: AMN were set to Intrinsic factor receptor deficiency due to AMN mutations (Disorders of cobalamin absorption, transport and metabolism); Proteinuric renal disease; Unexplained kidney failure in young people |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | ALAD |
Ellen McDonagh gene: ALAD was added gene: ALAD was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: ALAD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ALAD were set to 27604308 Phenotypes for gene: ALAD were set to {Lead poisoning, susceptibility to} 612740; Acute hepatic porphyria (Acute neuropathic porphyrias); Porphyria, acute hepatic 612740 |
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| Likely inborn error of metabolism - targeted testing not possible v0.4 | ABCB11 |
Ellen McDonagh gene: ABCB11 was added gene: ABCB11 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: ABCB11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ABCB11 were set to 27604308 Phenotypes for gene: ABCB11 were set to Progressive familial intrahepatic cholestasis type 2 (Disorders of bile acid metabolism and transport); Cholestasis, benign recurrent intrahepatic, 2 605479; Cholestasis, progressive familial intrahepatic 2 601847 |
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