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- Title
A Māori specific RFC1 pathogenic repeat configuration in CANVAS, likely due to a founder allele.
- Authors
Beecroft, Sarah J; Cortese, Andrea; Sullivan, Roisin; Yau, Wai Yan; Dyer, Zoe; Wu, Teddy Y; Mulroy, Eoin; Pelosi, Luciana; Rodrigues, Miriam; Taylor, Rachael; Mossman, Stuart; Leadbetter, Ruth; Cleland, James; Anderson, Tim; Ravenscroft, Gianina; Laing, Nigel G; Houlden, Henry; Reilly, Mary M; Roxburgh, Richard H
- Abstract
Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) is a recently recognized neurodegenerative disease with onset in mid- to late adulthood. The genetic basis for a large proportion of Caucasian patients was recently shown to be the biallelic expansion of a pentanucleotide (AAGGG)n repeat in RFC1. Here, we describe the first instance of CANVAS genetic testing in New Zealand Māori and Cook Island Māori individuals. We show a novel, possibly population-specific CANVAS configuration (AAAGG)10-25(AAGGG)exp, which was the cause of CANVAS in all patients. There were no apparent phenotypic differences compared with European CANVAS patients. Presence of a common disease haplotype among this cohort suggests this novel repeat expansion configuration is a founder effect in this population, which may indicate that CANVAS will be especially prevalent in this group. Haplotype dating estimated the most recent common ancestor at ∼1430 ce. We also show the same core haplotype as previously described, supporting a single origin of the CANVAS mutation.
- Subjects
NEW Zealand; OLDER people; CEREBELLAR ataxia; CANVAS; ALLELES; NEURODEGENERATION; VESTIBULAR apparatus diseases; CEREBELLUM degeneration
- Publication
Brain: A Journal of Neurology, 2020, Vol 143, Issue 9, p2673
- ISSN
0006-8950
- Publication type
journal article
- DOI
10.1093/brain/awaa203