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| Ataxia v2.237 | XPA | Bryony Thompson Marked gene: XPA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.237 | XPA | Bryony Thompson Gene: xpa has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.237 | XPA | Bryony Thompson Classified gene: XPA as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.237 | XPA | Bryony Thompson Gene: xpa has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.236 | XPA |
Bryony Thompson gene: XPA was added gene: XPA was added to Ataxia. Sources: Literature Mode of inheritance for gene: XPA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: XPA were set to 38040034; 36893274; 35699229; 31478152; 30077970 Phenotypes for gene: XPA were set to xeroderma pigmentosum group A, MONDO:0010210 Review for gene: XPA was set to GREEN Added comment: Biallelic XPA variants cause xeroderma pigmentosum group A. Ataxia can be a feature of the condition. Sources: Literature |
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| Ataxia v2.156 | PDHA1 |
Bryony Thompson gene: PDHA1 was added gene: PDHA1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: PDHA1 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: PDHA1 were set to 41760389; 35132535; 31673819; 29756269; 26014431 Phenotypes for gene: PDHA1 were set to pyruvate dehydrogenase E1-alpha deficiency, MONDO:0010717 Review for gene: PDHA1 was set to GREEN Added comment: Four independent families (PMID 31673819, PMID 26014431, PMID 35132535, PMID 29756269) with X‑linked PDHA1 loss‑of‑function or de novo missense variants present with cerebellar ataxia, developmental delay, lactic acidosis and other neurological signs; an additional prenatal case (PMID 41760389) expands the phenotypic spectrum. Sources: Literature |
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| Ataxia v2.136 | NOTCH2NLC_NIID_GGC |
Bryony Thompson changed review comment from: NM_001364012.2:c.-164GGC[X] Expanded repeat in NOTCH2NLC sequence is (GGC)9(GGA)2(GGC)2. Large number of families and sporadic cases reported with expansions, with a range of neurodegenerative phenotypes, including: dementia, Parkinsonism/tremor, peripheral neuropathy, leukoencephalopathy, myopathy, motor neurone disease. Normal repeat range: 4-40, 1 control had 61 repeats and may have been a presymptomatic carrier. Intermediate range: 41-60 identified in Parkinson's disease Pathogenic repeat range: >=60-520 Mechanism of disease is translation of repeat expansion into a toxic polyglycine protein, identified in both mouse models and tissue samples from affected individuals. Sources: Expert list; to: NM_001364012.2:c.-164GGC[X] Expanded repeat in NOTCH2NLC sequence is (GGC)9(GGA)2(GGC)2. Large number of families and sporadic cases reported with expansions, with a range of neurodegenerative phenotypes, including: dementia, Parkinsonism/tremor, peripheral neuropathy, leukoencephalopathy, myopathy, motor neurone disease, ataxia. Normal repeat range: 4-40, 1 control had 61 repeats and may have been a presymptomatic carrier. Intermediate range: 41-60 identified in Parkinson's disease Pathogenic repeat range: >=60-520 Mechanism of disease is translation of repeat expansion into a toxic polyglycine protein, identified in both mouse models and tissue samples from affected individuals. Sources: Expert list |
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| Ataxia v2.64 | GLS |
Bryony Thompson gene: GLS was added gene: GLS was added to Ataxia. Sources: Literature Mode of inheritance for gene: GLS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GLS were set to 38877099; 38260514; 35913761; 30970188 Phenotypes for gene: GLS were set to glutaminase deficiency, MONDO:0600001 Review for gene: GLS was set to GREEN Added comment: PMID 30970188 reports three families and PMID 35913761 reports two families (total five families, six patients) with biallelic GLS loss‑of‑function variants (5'UTR repeat expansions, frameshift, nonsense or missense coding changes) causing early‑onset developmental delay, progressive cerebellar ataxia and markedly elevated plasma glutamine. Functional studies show ~4‑fold reduced GLS mRNA in patient iPSCs, markedly decreased enzyme activity in patient fibroblasts, and zebrafish glsa knockdown recapitulating neurodevelopmental defects, though rescue experiments are lacking. These findings align with the Ataxia panel because progressive ataxia is a core feature of the panel’s scope of neurological disorders with ataxia. Sources: Literature |
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| Ataxia v1.136 | CACNA1A_SCA6_CAG |
Bryony Thompson STR: CACNA1A_SCA6_CAG was added STR: CACNA1A_SCA6_CAG was added to Ataxia. Sources: Expert List Mode of inheritance for STR: CACNA1A_SCA6_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: CACNA1A_SCA6_CAG were set to 20301319; 29325606 Phenotypes for STR: CACNA1A_SCA6_CAG were set to Spinocerebellar ataxia 6 MIM#183086; Episodic ataxia, type 2 MIM#108500 Review for STR: CACNA1A_SCA6_CAG was set to GREEN STR: CACNA1A_SCA6_CAG was marked as clinically relevant STR: CACNA1A_SCA6_CAG was marked as current diagnostic Added comment: NM_023035.2:c.6929_6931CAG[X] PolyQ expansion alters gene binding, impairs transcription factor function, and is toxic to cells expressing the α1ACT – effects consistent with a loss of function Normal: ≤18 repeats Questionable significance: 19 CAG repeats Full penetrance: ≥20 repeats Sources: Expert List |
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| Ataxia v1.47 | ATXN2_SCA2_CAG |
Bryony Thompson STR: ATXN2_SCA2_CAG was added STR: ATXN2_SCA2_CAG was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for STR: ATXN2_SCA2_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: ATXN2_SCA2_CAG were set to 40741828 Phenotypes for STR: ATXN2_SCA2_CAG were set to Spinocerebellar ataxia type 2 MONDO:0008458 Review for STR: ATXN2_SCA2_CAG was set to GREEN STR: ATXN2_SCA2_CAG was marked as clinically relevant STR: ATXN2_SCA2_CAG was marked as current diagnostic Added comment: Cohort of paediatric-onset SCA2 cases. The infantile onset group (n=9) had expansions ≥88 repeats, and the juvenile onset group (n=13) had expansions ≥43 repeats. Paediatric SCA2 phenotype includes developmental delay and seizures (infantile-onset) and cerebellar degeneration similar to adults in the juvenile group. Sources: Literature |
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| Ataxia v0.261 | CAD |
chirag patel gene: CAD was added gene: CAD was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: CAD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CAD were set to PMID: 32820246 Phenotypes for gene: CAD were set to Epileptic encephalopathy, early infantile, 50; OMIM # 616457 Review for gene: CAD was set to GREEN gene: CAD was marked as current diagnostic Added comment: 2020 series: 6/20 patients reported had ataxia relating to cerebellar atrophy, which is an expansion to the phenotype. Sources: Literature |
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| Ataxia v0.212 | CACNA1A | Bryony Thompson Added comment: Comment on list classification: Ataxia can be caused by a triplet repeat expansion in this gene, which is not detectable with current WES/WGS technologies. However, SNVs have also been reported as disease-causing. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.117 | FXN |
Bryony Thompson gene: FXN was added gene: FXN was added to Ataxia - paediatric. Sources: Expert list STR tags were added to gene: FXN. Mode of inheritance for gene: FXN was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FXN were set to Friedreich ataxia MIM#229300 Review for gene: FXN was set to GREEN Added comment: Onset usually before adolescence. Most common genetic abnormality is the trinucleotide repeat expansion, but also SNVs and indels reported. Sources: Expert list |
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