A Māori specific RFC1 pathogenic repeat configuration in CANVAS, likely due to a founder allele
| Autor: | Teddy Y. Wu, Henry Houlden, Zoe Dyer, Rachael W. Taylor, Wai Yan Yau, Andrea Cortese, Sarah J. Beecroft, Roisin Sullivan, Stuart Mossman, Richard Roxburgh, Ruth Leadbetter, Luciana Pelosi, Nigel G. Laing, Mary M. Reilly, Tim J. Anderson, James C. Cleland, Eoin Mulroy, Gianina Ravenscroft, Miriam Rodrigues |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male Native Hawaiian or Other Pacific Islander Cerebellar Ataxia Bilateral Vestibulopathy geography.island Population Biology Cook island Cohort Studies 03 medical and health sciences 0302 clinical medicine medicine Humans Allele Replication Protein C education Alleles Genetic testing Aged Genetics geography education.field_of_study medicine.diagnostic_test Cerebellar ataxia Haplotype Middle Aged Founder Effect Pedigree 030104 developmental biology Female Neurology (clinical) medicine.symptom Trinucleotide repeat expansion 030217 neurology & neurosurgery Founder effect Reports |
| Zdroj: | Brain |
| ISSN: | 1460-2156 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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