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Gene-disease assertions not curated here (add link or write note):
Disease | Spinocerebellar ataxia 12 |
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Inheritance | Autosomal dominant |
Prevalence | <1 / 1 000 000 Source: Orphanet |
Rapid or full curation? | |
ClinGen / GenCC / BabySeq / HGMD / OMIM | ClinGen - none. GenCC - Strong (Invitae). BabySeq - none. HGMD papers below. Holmes 1999 PMID: 10581021 Wang 2011 PMID: 21743138 - can’t access, DOI error. Brusco 2004 PMID: 15148151 Rossi 2019 PMID: 31190316 Wan 2021 PMID: 34284285 |
Clinical Validity Scoring Notes and points | Source: |
Clinical Validity Points Total | Source: |
Clinical Validity Classification | Expand |
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| title | Classifications (pts) |
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| Definitive (12pts) Strong (12pts) Moderate (7-11pts) Limited (0.1-6pts) No genetic evidence Refuted Disputed |
| Source: |
Molecular Mechanism | Expand |
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| Loss of function Gain of function Dominant negative Unknown Other |
| Loss of function / Gain of function / Dominant Negative Short Tandem Repeat - CAG repeats in the 5’UTR Review: Stripy - Normal: 7-31. Pathogenic ≥51 STRchive - Normal 4-32. Pathogenic ≥51 gnomAD Normal 4-32. Pathogenic ≥51 Depienne (review) PMID: - Normal 4-32, pathogenic ≥43-78. Mayo - none
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Penetrance | Expand |
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| Complete (100%) High (≥80%) Moderate (<80% and >20%) Low (≤20%) |
(list source/PMID) | Source: |
Age of Onset | Expand |
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| Congenital Pediatric Adolescent Adulthood Late adulthood |
(list source/PMID) | |
Severity | Expand |
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| Embryonic lethal - presence of a pathogenic variant or variants is not compatible with life. The penetrance must be complete.
Severe - presence of a pathogenic variant or variant(s) results in significantly reduced fitness. The penetrance must be complete or high.
Moderate - significant morbidity or mortality due to clinical features, but fitness may not be reduced, or penetrance is reduced.
Mild - Presence of a variant or variant(s) is not associated with reduced fitness, no significant morbidity or mortality, and/or penetrance is low.
None - presence of a variant results in no phenotype. An example is recessive disorders in which no phenotype is reported in carriers. |
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Clinical Features | Most individuals present in the fourth decade with upper extremity tremor, progressing over several decades to include head tremor, gait ataxia, dysmetria, dysdiadokinesis, hyperreflexia, paucity of movement, abnormal eye movements and, in the oldest subjects, dementia. Cortical and cerebellar atrophy on MRI/CT in some - PMID: 10581021 Sources: |
HPO Terms https://hpo.jax.org/app/ | |
Gene SOPs & Notes | LINK if SOP is a long document. Short notes if it is easy to digest. eg. Last known truncating variant |
Curation Summary | Expand |
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| - The @GENE@ is associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs). - Variable expression or severity:
The severity and expressivity of the disorder is highly variable, even within families.
- If multiple conditions associated with the gene:
It has also been associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs). - Limited evidence gene: The PCNA gene has been reported in individuals with early onset autosomal recessive ataxia (PMID: 33426167, 24911150), however, evidence supporting this gene-dIsease relationship is limited |
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Case ID, Curator name, Date, Jira ticket link | |
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