Screening for FXTAS in 95 Spanish patients negative for Huntington disease.
Fragile X syndrome is the most common form of hereditary mental retardation. The molecular basis of this syndrome is mainly a CGG expansion in the 5' untranslated region of the FMR1 gene. Expansions with more than 200 CGG repeats abolish gene expression causing the classical fragile X phenotype. Premutation carriers (55-200 CGG) have normal cognitive function with increased risk of developing premature ovarian failure and fragile X-associated tremor-ataxia syndrome (FXTAS). Some clinical features associated with FXTAS, such as tremor, gait ataxia, cognitive decline, and generalized brain atrophy, are also seen in other movement disorders. Ninety-five patients referred for HD, who tested negative for the expansion in the IT15 gene, were screened for FMR1 CGG-repeat expansion. One FMR1 premutation male carrier was detected, giving an FXTAS frequency of 1.6%. Our results highlight that FXTAS is still not well diagnosed; therefore, we recommend FMR1 premutation screenings in all patients with late-onset tremor, ataxia, and cognitive dysfunction.
Rodriguez-Revenga
Laia
L
Biochemistry and Molecular Genetics Department, Hospital Clínic, and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Santos
M Mònica
MM
Sánchez
Aurora
A
Pujol
Montserrat
M
Gómez-Anson
Beatriz
B
Badenas
Celia
C
Jiménez
Dolores
D
Madrigal
Irene
I
Milà
Montserrat
M
D020121:5' Untranslated Regions; D000368:Aged; D001259:Ataxia / Q000235:genetics; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000235:genetics*; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D013030:Spain; D014202:Tremor / Q000235:genetics; D019680:Trinucleotide Repeat Expansion
D020121:5' Untranslated Regions; D051860:Fragile X Messenger Ribonucleoprotein 1; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C497683:FMR1 protein, human; C086055:HTT protein, human