RFC1 Repeat Expansion Testing
Description
Biallelic pathogenic pentanucleotide repeat expansions within the second intron of the RFC1 gene have been associated with autosomal recessive cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). The repeat region is highly polymorphic with variability in both repeat motif and size.
Pathogenicity is dependent upon repeat length according to the following ranges 1-4:
Normal Alleles | Mutable Normal Alleles | Intermediate/Uncertain Alleles | Reduced Penetrance Alleles | Full Penetrance Alleles |
11-200 AAAAG, 40-600 AAAGG* | - | 100-249 AAGGG** | - | 250 or more AAGGG, 600 or more AAAGG, 1000 ACAGG or more |
*Different repeats have been described for normal alleles. These are the most commonly reported, with 11 AAAAG repeats being the most common allele.
**Limited clinical evidence exists for AAAGG repeats fewer than 600 and ACAGG repeats fewer than 1000.
Note: Carriers are not reported. Also, as CANVAS is typically adult onset, RFC1 repeat expansions are not reported in minors in comprehensive analyses.
Tests That Analyze RFC1 Repeats
- Genomic Unity® 2.0
- Genomic Unity® Whole Genome Analysis
- 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 Unity® Neuromuscular Disorders Analysis
- Genomic Unity® Neuropathies Analysis
Additional Resources
First-Line Testing, Lighting Up the Undetectable
A 70-year-old male presented with a clinical CANVAS diagnosis. Variantyx testing identified two fully expanded RFC1 alleles with >250 AAGGG repeats.
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.
Expanded STR Detection Capability Enables Variantyx to Diagnose Additional Genetic Disorders
Press release: Variantyx, a leader in genomic precision medicine, today announced that the set of short tandem repeat (STR) expansions detected by its Genomic Unity® line of whole genome-based tests has been expanded.
