Beecroft, SJ;
Cortese, A;
Sullivan, R;
Yau, WY;
Dyer, Z;
Wu, TY;
Mulroy, E;
... Roxburgh, RH; + view all
(2020)
A Māori specific RFC1 pathogenic repeat configuration in CANVAS, likely due to a founder allele.
Brain
, 143
(9)
pp. 2673-2680.
10.1093/brain/awaa203.
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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.
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