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

TitleA novel RFC1 repeat motif (ACAGG) in two Asia-Pacific CANVAS families.
Publication TypeJournal Article
Year of Publication2020
AuthorsScriba, CK, Beecroft, SJ, Clayton, JS, Cortese, A, Sullivan, R, Yau, WYan, Dominik, N, Rodrigues, M, Walker, E, Dyer, Z, Wu, TY, Davis, MR, Chandler, DC, Weisburd, B, Houlden, H, Reilly, MM, Laing, NG, Lamont, PJ, Roxburgh, RH, Ravenscroft, G
Date Published2020 10 01
KeywordsAged, Asian Continental Ancestry Group, Bilateral Vestibulopathy, Cerebellar Ataxia, Cohort Studies, DNA Repeat Expansion, Female, Humans, Indonesia, Male, Middle Aged, Pedigree, Replication Protein C

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.

Alternate JournalBrain
PubMed ID33103729
PubMed Central IDPMC7780484
Grant ListUM1 HG008900 / HG / NHGRI NIH HHS / United States
U54 NS065712 / NS / NINDS NIH HHS / United States
R01 HG009141 / HG / NHGRI NIH HHS / United States
MR/T001712/1 / MR / Medical Research Council / United Kingdom
G0601943 / MR / Medical Research Council / United Kingdom