A novel RFC1 repeat motif (ACAGG) in two Asia-Pacific CANVAS families

Carolin K Scriba, Sarah J Beecroft, Joshua S Clayton, Andrea Cortese, Roisin Sullivan, Wai Yan Yau, Natalia Dominik, Miriam Rodrigues, Elizabeth Walker, Zoe Dyer, Teddy Y Wu, Mark R Davis, David C Chandler, Ben Weisburd, Henry Houlden, Mary M Reilly, Nigel G Laing, Phillipa J Lamont, Richard H Roxburgh, Gianina Ravenscroft

Research output: Contribution to journalArticle

Abstract

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a progressive late-onset, neurological disease. Recently, a pentanucleotide expansion in intron 2 of RFC1 was identified as the genetic cause of CANVAS. We screened an Asian-Pacific cohort for CANVAS and identified a novel RFC1 repeat expansion motif, (ACAGG)exp, in three affected individuals. This motif was associated with additional clinical features including fasciculations and elevated serum creatine kinase. These features have not previously been described in individuals with genetically-confirmed CANVAS. Haplotype analysis showed our patients shared the same core haplotype as previously published, supporting the possibility of a single origin of the RFC1 disease allele. We analysed data from >26 000 genetically diverse individuals in gnomAD to show enrichment of (ACAGG) in non-European populations.

Original languageEnglish
Pages (from-to)2904-2910
Number of pages7
JournalBrain: A Journal of Neurology
Volume143
Issue number10
DOIs
Publication statusPublished - Oct 2020

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