ATXN1 Repeat Expansion Testing
Description
Pathogenic CAG repeat expansions in the ATXN1 gene have been associated with autosomal dominant spinocerebellar ataxia 1 (SCA1). The pathogenic repeat expansions lead to expanded polyglutamine tracts that appear to cause protein misfolding resulting in insoluble nuclear inclusions that are toxic to cells.
Pathogenicity is dependent upon CAG repeat length according to the following ranges 1-3:
Normal Alleles | Mutable Normal Alleles | Intermediate or Uncertain Alleles | Reduced Penetrance Alleles | Full Penetrance Alleles |
6-35 (uninterrupted) 36-44 (interrupted)* | 36-38** | - | - | 39-44 (uninterrupted) 46 or more (interrupted)* |
*CAT repeats within the CAG repeat region influence the pathogenicity of the allele.
**Alleles in the mutable normal range may either expand or contract during transmission to offspring.
Note: As SCA1 is typically adult onset, ATXN1 repeat expansions are not reported in minors in comprehensive analyses.
Tests That Analyze ATXN1 Repeats
- Genomic Unity® 2.0
- Genomic Unity® Whole Genome Analysis
- Genomic Unity® Lightning Genome Analysis – Pediatric
- Genomic Unity® Lightning Genome Analysis – Standard
- Genomic Unity® Exome Plus Analysis
- Genomic Unity® Exome Analysis
- Genomic Unity® Movement Disorders Analysis
- Genomic Unity® Comprehensive Ataxia Analysis
- Genomic Unity® Ataxia Repeat Expansion Analysis
- Genomic Inform®
Additional Resources
Same Symptoms, Different Diagnoses
Five patients ranging in age from 59-70 presented with similar symptoms of progressive cerebellar ataxia, gait imbalance, progressive sensory neuropathy and dysphagia and/or dysarthria. Each received a different diagnosis with Variantyx testing.