title: FXTAS is rare among Portuguese patients with movement disorders: FMR1 premutations may be associated with a wider spectrum of phenotypes.
abstract: The fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by expansions of 55-200 CGG repeats in the 5'UTR of the FMR1 gene. These FMR1 premutation expansions have relatively high frequency in the general population. To estimate the frequency of FMR1 premutations among Portuguese males with non-familial, late-onset movement disorders of unknown etiology, we assessed CGG repeat size in males with disease onset after the age of 50 and negative or unknown family history for late-onset movement disorders, who were sent for SCA, HD, or PD genetic testing at a reference laboratory. The selected patients had a primary clinical diagnosis based on one of the following cardinal features of FXTAS: ataxia, tremor, or cognitive decline. A total of 86 subjects were genotyped for the CGG repeat in the FMR1 gene. We detected one patient with an expansion in the premutation range. The frequency of FMR1 premutations was 1.9% (1/54) in our group of patients with ataxia as the primary clinical feature, and 1.2% (1/86) in the larger movement disorders group. In the family of the FXTAS case, premutation-transmitting females presented a history of psychiatric symptoms, suggesting that, given the wide phenotypical expression of the premutation in females, neuropsychiatric surveillance is necessary. In conclusion, genetic testing for FXTAS should be made available to patients with adult-onset movement disorders to enable adequate genetic counseling to family members.
authors.affiliation: UnIGENe, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Seixas
authors.forename: José
authors.initials: J
authors.lastname: Vale
authors.forename: Paula
authors.initials: P
authors.lastname: Jorge
authors.forename: Isabel
authors.initials: I
authors.lastname: Marques
authors.forename: Rosário
authors.initials: R
authors.lastname: Santos
authors.forename: Isabel
authors.initials: I
authors.lastname: Alonso
authors.forename: Ana M
authors.initials: AM
authors.lastname: Fortuna
authors.forename: Jorge
authors.initials: J
authors.lastname: Pinto-Basto
authors.forename: Paula
authors.initials: P
authors.lastname: Coutinho
authors.forename: Russell L
authors.initials: RL
authors.lastname: Margolis
authors.forename: Jorge
authors.initials: J
authors.lastname: Sequeiros
authors.forename: Isabel
authors.initials: I
authors.lastname: Silveira
mesh_terms: D000368:Aged; D001259:Ataxia / Q000150:complications / Q000235:genetics*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000150:complications / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011174:Portugal; D014202:Tremor / Q000150:complications / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human