title: FXTAS in spanish patients with ataxia: support for female FMR1 premutation screening.
abstract: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a newly described disorder characterized by progressive action tremor and ataxia that occurs in premutation carriers of the FMR1 gene. The incidence of FMR1 premutated carriers in the general population is relatively high, and therefore FXTAS might explain a considerable number of sporadic, late-onset ataxias. To better establish the prevalence of FXTAS among undiagnosed Spanish patients with ataxia, we have performed a FMR1 premutation screening. Our results evidenced three individuals carrying premutated alleles, giving an estimated FXTAS prevalence of 1.95% among patients with late-onset ataxia (1.15% for males and 3% for females). Molecular characterization of premutation carriers evidences lower fragile X mental retardation 1 protein levels and increased FMR1 mRNA levels. Clinical and neuroimaging findings support FXTAS diagnosis in these patients. Because of the high prevalence of FMR1 premutation in the general population, the description and characterization of the FXTAS syndrome is of great interest as it may represent one of the more common monogenic causes of ataxia, tremor, and dementia. The results obtained in this study demonstrate that FXTAS should be incorporated to spinocerebellar ataxia genetic screening protocols. Early diagnosis of these patients benefits not only them but also the rest of the family that should be advised for the fragile X syndrome.
authors.affiliation: Biochemistry and Molecular Genetics Department, Hospital Clínic, Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Rodriguez-Revenga
authors.forename: Beatriz
authors.initials: B
authors.lastname: Gómez-Anson
authors.forename: Esteban
authors.initials: E
authors.lastname: Muñoz
authors.forename: Dolores
authors.initials: D
authors.lastname: Jiménez
authors.forename: Monica
authors.initials: M
authors.lastname: Santos
authors.forename: Mar
authors.initials: M
authors.lastname: Tintoré
authors.forename: Gisela
authors.initials: G
authors.lastname: Martín
authors.forename: Luis
authors.initials: L
authors.lastname: Brieva
authors.forename: Montserrat
authors.initials: M
authors.lastname: Milà
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001259:Ataxia / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D013030:Spain
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human