| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Ataxia - adult onset v1.4 | SCA27B | Bryony Thompson Marked STR: SCA27B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v1.4 | SCA27B | Bryony Thompson Str: sca27b has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v1.4 | SCA27B | Bryony Thompson Classified STR: SCA27B as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v1.4 | SCA27B | Bryony Thompson Str: sca27b has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v1.3 | SCA27B |
Bryony Thompson STR: SCA27B was added STR: SCA27B was added to Ataxia - adult onset. Sources: Literature Mode of inheritance for STR: SCA27B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA27B were set to 37165652; 36516086; 36493768 Phenotypes for STR: SCA27B were set to Spinocerebellar ataxia type 27B MONDO:0012247; Spinocerebellar ataxia 50; late-onset cerebellar ataxias (LOCAs) Review for STR: SCA27B was set to GREEN STR: SCA27B was marked as clinically relevant Added comment: NM_175929.3(FGF14):c.208+239747CTT[X] Expansions of 250 or more GAA repeat units were associated with late-onset cerebellar ataxia in a French-Canadian (OR: 105.60 [95% CI=31.09-334.20], p<0.001) and a German (OR: 8.76 [95% CI=3.45-20.84], p<0.001) case-control series. Additionally, expanded alleles greater than (GAA)332 are pathogenic and fully penetrant in a combined Australian and German dataset (p = 6.0 × 10−8, OR = 72 [95% CI = 4.3–1,227]). Whereas, alleles in the range of (GAA)250-334 are likely to be pathogenic with reduced penetrance (p = 0.0015, OR = 3.6 [95% CI = 1.6–7.9]). 250-300 repeats in the incompletely penetrant range >300 is fully penetrant for ataxia Sources: Literature |
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| Ataxia - adult onset v0.164 | PNPT1 |
Zornitza Stark gene: PNPT1 was added gene: PNPT1 was added to Ataxia - adult onset. Sources: Literature Mode of inheritance for gene: PNPT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PNPT1 were set to 35411967 Phenotypes for gene: PNPT1 were set to Spinocerebellar ataxia 25, MIM# 608703 Review for gene: PNPT1 was set to AMBER Added comment: Three families reported with heterozygous variants and SCA25. Incomplete penetrance in one of the families. In the third family, the variant was inherited from an asymptomatic 80+ year old. Note bi-allelic variants in this gene cause a mitochondrial disorder. Exact mechanism through which mono-allelic variants cause SCA25 not elucidated: authors speculate abnormal accumulation of mitochondrial RNA with subsequent leakage into the cytosol that may trigger a type 1 interferon response leading to neuroinflammation with neuronal dysfunction or neuronal loss. Sources: Literature |
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| Ataxia - adult onset v0.73 | SCA2 | Bryony Thompson Classified STR: SCA2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v0.73 | SCA2 | Bryony Thompson Str: sca2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia - adult onset v0.72 | SCA2 |
Bryony Thompson STR: SCA2 was added STR: SCA2 was added to Ataxia - adult onset. Sources: Expert list STR tags were added to STR: SCA2. Mode of inheritance for STR: SCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA2 were set to 29325606; 20301452 Phenotypes for STR: SCA2 were set to Spinocerebellar ataxia 2 MIM#183090 Review for STR: SCA2 was set to GREEN STR: SCA2 was marked as clinically relevant Added comment: NM_002973.3:c.496_498CAG[X] Toxic protein aggregation is mechanism of disease Benign: ≤31 repeats (homozygous 31/31 repeats reported for recessive SCA2) Uncertain: 32 repeats ALS risk allele: 30-32 repeats Reduced penetrance: 33-34 repeats, may not develop symptoms or only very late in life Full penetrance: ≥35 repeats Interruption of a CAG expanded allele by a CAA repeat does not mitigate the pathogenicity of the repeat size, but may enhance the meiotic stability of the repeat Sources: Expert list |
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| Ataxia - adult onset v0.37 | ATXN2 |
Bryony Thompson gene: ATXN2 was added gene: ATXN2 was added to Ataxia - adult onset. Sources: Expert list STR tags were added to gene: ATXN2. Mode of inheritance for gene: ATXN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATXN2 were set to 8896555; 8896556 Phenotypes for gene: ATXN2 were set to Spinocerebellar ataxia 2 MIM#183090 Mode of pathogenicity for gene: ATXN2 was set to Other Review for gene: ATXN2 was set to GREEN Added comment: Mean age of onset of ataxia in third decade: (CAG)n repeat located in the 5-prime end of the coding region of the ATXN2 gene. SCA2 patient chromosomes usually contain expanded repeats ranging in size from 35 to 59 units. Sources: Expert list |
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