FIRST-LINE TESTING, LIGHTING UP THE UNDETECTABLE
Genomic Unity® Case Study

Biallelic RFC1 expansion confirms clinical CANVAS diagnosis

Clinical presentation

A 70-year-old male presented with the following symptoms:

  • Progressive ataxia with onset in late 50’s
  • Progressive sensory neuropathy including decreased lower extremity vibration and position sense bilaterally, positive Romberg test
  • Dysphagia
  • Vision changes

Previous genetic testing

No previous genetic testing was reported.

Genomic Unity® Testing

was ordered because of its ability to identify all major variant types in a single test.

Results and interpretation

Variantyx Genomic Unity® testing identified two fully expanded RFC1 alleles with >250 AAGGG repeats.

The expansions were confirmed internally using Oxford Nanopore long-read sequencing.

Diagnosis: Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS)

IGV view of RFC1 variants

Uniform data from WGS clearly identifies the biallelic expansion.

The Variantyx Difference

Why was this biallelic RFC1 expansion identified by Genomic Unity® testing, when it would have been missed by other ataxia tests?

  • Repeats expansions can not be detected by standard genetic tests, including panels and exomes.
    Variantyx genome analysis detects all major variant types in a single test including small sequence changes, structural variants, repeat expansions and mitochondrial variants – which is critical for first-line testing of ataxia patients.

  • Repeat can be detected by PCR and Southern blotting, but RFC1 would have to be specifically targeted. Very few available ataxia tests are able to overcome the challenges of this locus.
    Variantyx genome analysis detects repeat expansions in >35 genes, including RFC1. Variantyx is one of the first labs to offer RFC1 testing.

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