The genetic aetiology of late-onset chronic progressive cerebellar ataxia

Wardle, Mark, Majounie, Elisa ORCID: https://orcid.org/0000-0003-2800-1091, Muzaimi, Mustapha B., Williams, Nigel Melville ORCID: https://orcid.org/0000-0003-1177-6931, Morris, Huw Rees and Robertson, Neil ORCID: https://orcid.org/0000-0002-5409-4909 2009. The genetic aetiology of late-onset chronic progressive cerebellar ataxia. Journal of Neurology 256 (3) , pp. 343-348. 10.1007/s00415-009-0015-2

Full text not available from this repository.

Abstract

Background An increasing number of dominant and recessive disorders have been associated with late onset chronic progressive ataxia (LOCA) complicating the formulation of a rational diagnostic strategy. Furthermore, there is marked geographic and ethnic variation in the relative importance of these individual disorders and the cause of such observed variation remains unexplained. Methods We have systematically investigated a populationbased cohort of patients with chronic progressive LOCA for SCA 1,2,3,6,7,8,10,12,17, FXTAS and FRDA. In addition we have examined repeat length polymorphism in chromosomes from a genetically homogeneous and representative control population to investigate the association of high-normal repeats and disease prevalence. Results A total of 178 patients including 55 familial cases segregating in 38 kindreds and 123 sporadic were investigated. Pathological expansions were identified in 11/38 (28.9 %) of families and in 5/123 (4.1 %) of sporadic patients. The most frequent diagnoses were SCA6 (6 families and 1 sporadic patient), DRPLA (4 families) and SCA8 (1 family). In addition, one elderly female patient was identified with “possible FXTAS”. Six (2 %) control patients were noted to have expanded SCA8 alleles. Conclusions SCA6 and DRPLA were the most frequent genetic diagnoses identified. Patterns of highnormal allele frequency in this UK population were distinct compared to other ethnic groups but this was poorly predictive of the distribution of disease in this region. The relative contribution of new mutation formation and founder effects to the prevalence of familial ataxia is uncertain, and further exploration of these factors will require detailed analysis of disease allele haplotypes and meiotic instability of intermediate length alleles.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General)
Uncontrolled Keywords:	prevalence studies, spinocerebellar ataxia, trinucleotide repeat diseases, FXTAS, cerebellum
Publisher:	Springer
ISSN:	0340-5354
Last Modified:	19 Oct 2022 10:05
URI:	https://orca.cardiff.ac.uk/id/eprint/23185

Citation Data

Cited 22 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item