FMR1 CGG repeat length predicts motor dysfunction in premutation carriers.

Détails

Ressource 1Télécharger: 18057320_Postprint.pdf (715.37 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_C6865B44438D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
FMR1 CGG repeat length predicts motor dysfunction in premutation carriers.
Périodique
Neurology
Auteur(s)
Leehey M.A., Berry-Kravis E., Goetz C.G., Zhang L., Hall D.A., Li L., Rice C.D., Lara R., Cogswell J., Reynolds A., Gane L., Jacquemont S., Tassone F., Grigsby J., Hagerman R.J., Hagerman P.J.
ISSN
1526-632X (Electronic)
ISSN-L
0028-3878
Statut éditorial
Publié
Date de publication
12/2008
Peer-reviewed
Oui
Volume
70
Numéro
16 Pt 2
Pages
1397-1402
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Résumé
BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a recently described, underrecognized neurodegenerative disorder of aging fragile X mental retardation 1 (FMR1) premutation carriers, particularly men. Core motor features are action tremor, gait ataxia, and parkinsonism. Carriers have expanded CGG repeats (55 to 200); larger expansions cause fragile X syndrome, the most common heritable cause of mental retardation and autism. This study determines whether CGG repeat length correlates with severity and type of motor dysfunction in premutation carriers.
METHODS: Persons aged >or=50 years with a family history of fragile X syndrome underwent structured videotaping. Movement disorder neurologists, blinded to carrier status, scored the tapes using modified standardized rating scales. CGG repeat length analyses for women incorporated the activation ratio, which measures the percentage of normal active chromosome X alleles.
RESULTS: Male carriers (n = 54) had significantly worse total motor scores, especially in tremor and ataxia, than age-matched male noncarriers (n = 51). There was a trend toward a difference between women carriers (n = 82) and noncarriers (n = 39). In men, increasing CGG repeat correlated with greater impairment in all motor signs. In women, when activation ratio was considered, increasing CGG correlated with greater ataxia.
CONCLUSIONS: CGG repeat size is significantly associated with overall motor impairment in premutation carriers. Whereas this association is most pronounced for men and covers overall motor impairment-tremor, ataxia, and parkinsonism-the association exists for ataxia among women carriers. This is the first report of a significant correlation between the premutation status and a motor feature of fragile X-associated tremor/ataxia syndrome in women.
Mots-clé
Aged, Female, Fragile X Mental Retardation Protein/genetics, Fragile X Syndrome/complications, Fragile X Syndrome/diagnosis, Heterozygote Detection/methods, Humans, Male, Middle Aged, Movement Disorders/complications, Movement Disorders/genetics, Mutation/genetics, Predictive Value of Tests, Sex Factors, 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 15:42
Données d'usage