Size bias of fragile X premutation alleles in late-onset movement disorders

Détails

ID Serval
serval:BIB_77FC4C7A8E1C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Size bias of fragile X premutation alleles in late-onset movement disorders
Périodique
Journal of Medical Genetics
Auteur⸱e⸱s
Jacquemont  S., Leehey  M. A., Hagerman  R. J., Beckett  L. A., Hagerman  P. J.
ISSN
1468-6244
Statut éditorial
Publié
Date de publication
10/2006
Peer-reviewed
Oui
Volume
43
Numéro
10
Pages
804-9
Notes
Comparative Study
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't --- Old month value: Oct
Résumé
BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS), caused by premutation expansions (55-200 CGG repeats) of the FMR1 gene, shares clinical features with other movement disorders, particularly in the domains of gait ataxia, intention tremor and parkinsonism. However, the prevalence of FXTAS within other diagnostic categories is not well defined. METHODS: A meta-analysis was conducted of all published (n = 14) genetic screens for expanded FMR1 alleles to assess the prevalence and CGG-repeat size bias of FMR1 premutation alleles in those populations. RESULTS: In men with late-onset cerebellar ataxia, the prevalence of premutation alleles (1.5%; 16/1049) was 13 times greater than expected based on its prevalence in the general population (2%; 16/818 for age of onset >50 years; odds ratio 12.4; 95% confidence interval 1.6 to 93.5). Meta-analysis of CGG-repeat data for screened patients with premutation alleles shows a shift to larger repeat size than in the general population (p<0.001). 86% (19/22) of premutation alleles were larger than 70 repeats in the patients screened, whereas only approximately 22% of premutation alleles are larger than 70 repeats in the general population. CONCLUSIONS: Expanded FMR1 alleles contribute to cases of late-onset sporadic cerebellar ataxia, suggesting that FMR1 genetic testing should be carried out in such cases. The biased distribution of FMR1 allele sizes has substantial implications for genetic counselling of carriers with smaller alleles who are at a low risk of developing FXTAS, and suggests that the estimated prevalence of FXTAS among men >50 years of age in the general population may be two to threefold lower than the initial figure of 1 in 3000.
Mots-clé
Adult Age of Onset Aged Aged, 80 and over *Alleles Ataxia Bias (Epidemiology) Child Female Fragile X Mental Retardation Protein/genetics Fragile X Syndrome/epidemiology/*genetics Genetic Screening/methods/statistics & numerical data Humans Male Middle Aged Movement Disorders/epidemiology/*genetics Multiple System Atrophy/classification/epidemiology/genetics Parkinsonian Disorders/classification/epidemiology/genetics Prevalence Spinocerebellar Degenerations/classification/epidemiology/genetics Tremor Trinucleotide Repeat Expansion/genetics
Pubmed
Web of science
Création de la notice
28/02/2008 10:42
Dernière modification de la notice
20/08/2019 14:34
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