Update August 8, 2022
Truncating variants in the RFC1 gene have been identified in patients with clinically defined CANVAS in the compound heterozygous state with a repeat expansion in the RFC1 gene. We have identified seven such patients from five unrelated families (PMID 36289003). Sequencing of the RFC1 gene is indicated in CANVAS patients heterozygous for an RFC1 repeat expansion.
Update June 2021: The University of Chicago Genetic Services lab has been performing RFC1 repeat expansion testing since October of 2019. Orders for single gene RFC1 repeat expansion testing have a positive yield of over 40%. In samples submitted for the Ataxia Repeat Expansion panel, which includes RFC1, approximately 7% of cases have been positive for biallelic expansion of RFC1 (in comparison to SCA3, SCA8, and Friedreich ataxia which have a positive yield of approximately 2% each). Overall, when looking at all samples that have been tested for RFC1 repeat expansions there is a 19% positive yield.
October 2019: A biallelic intronic expansion in the RFC1 gene has recently been identified in the majority of patients with CANVAS (Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome) and in a proportion of late onset ataxia patients. Re-analysis of our negative ataxia cases has demonstrated biallelic repeat expansions in RFC1 in ~5% of the cases. RFC1 repeat expansion analysis has been added to our Ataxia Repeat Expansion Panel at no additional cost, making this panel more comprehensive. More details about our Ataxia Repeat Expansion Panel can be found here. RFC1 repeat expansion testing can also be ordered independently.