Penetrance of marked cognitive impairment in older male carriers of the FMR1 gene premutation.

Détails

ID Serval
serval:BIB_220688782453
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Penetrance of marked cognitive impairment in older male carriers of the FMR1 gene premutation.
Périodique
Journal of Medical Genetics
Auteur(s)
Sévin M., Kutalik Z., Bergman S., Vercelletto M., Renou P., Lamy E., Vingerhoets F.J., Di Virgilio G., Boisseau P., Bezieau S., Pasquier L., Rival J.M., Beckmann J.S., Damier P., Jacquemont S.
ISSN
1468-6244[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
46
Numéro
12
Pages
818-824
Langue
anglais
Résumé
BACKGROUND: Male carriers of the FMR1 premutation are at risk of developing the fragile X-associated tremor/ataxia syndrome (FXTAS), a newly recognised and largely under-diagnosed late onset neurodegenerative disorder. Patients affected with FXTAS primarily present with cerebellar ataxia and intention tremor. Cognitive decline has also been associated with the premutation, but the lack of data on its penetrance is a growing concern for clinicians who provide genetic counselling. METHODS: The Mattis Dementia Rating Scale (MDRS) was administered in a double blind fashion to 74 men aged 50 years or more recruited from fragile X families (35 premutation carriers and 39 intrafamilial controls) regardless of their clinical manifestation. Based on previous publications, marked cognitive impairment was defined by a score <or=123 on the MDRS. RESULTS: Both logistic and survival models confirmed that in addition to age and education level, premutation size plays a significant (p<0.01 and p<0.03 for logistic and survival model, respectively) role in cognitive impairment. The estimated penetrance of marked cognitive impairment in our sample (adjusted for the mean age 63.4 years and mean education level 9.7 years) for midsize/large (70-200 CGG) and small (55-69 CGG) premutation alleles was 33.3% (relative risk (RR) 6.5; p = 0.01) and 5.9% (RR 1.15; p = 0.9) respectively. Penetrance in the control group was 5.1%. CONCLUSIONS: Male carriers of midsize to large premutation alleles had a sixfold increased risk of developing cognitive decline and the risk increases with allele size. In addition, it was observed that cognitive impairment may precede motor symptoms. These data provide guidance for genetic counselling although larger samples are required to refine these estimates.
Mots-clé
Fragile-X Premutation, Dementia-Rating-Scale, Tremor/Ataxia Syndrome Fxtas, Parkinsons-Disease, Alzheimers-Disease, Normative Data, Population, Depression, Alleles, Cerebellar
Pubmed
Web of science
Création de la notice
15/12/2009 16:03
Dernière modification de la notice
20/08/2019 13:58
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