Screening for FMR-1 premutations in 122 older Flemish males presenting with ataxia.
Recently, Hagerman et al described the occurrence of a late-onset neurological disorder in five male carriers of the fragile-X (FMR-1) premutation. The major characteristics of this disorder, designated the Fragile-X Tremor Ataxia Syndrome (FXTAS), are progressive intention tremor, cerebellar ataxia and cognitive decline. Most cases of FXTAS published thus far were ascertained through families with a known fragile-X proband. Since cerebellar ataxia is one of the main cardinal features, we performed FMR-1 premutation screening in 122 male patients, older than 50 years, who were referred to us for testing of the spinocerebellar ataxia (SCA 1, 2, 3, 6, 7) genes and who were found to be negative. In this group of patients, we found five patients with an FMR-1 premutation. In four of them, a definite diagnosis of FXTAS could be made, based on the proposed diagnostic clinical and radiological criteria for FXTAS. In light of these figures, we recommend that FMR-1 analysis should be included in the molecular diagnostic work-up in the group of male ataxia patients older than 50 years.
Van Esch
Hilde
H
Centre for Human Genetics, University Hospital Leuven, Leuven, Belgium. Hilde.Vanesch@med.kuleuven.ac.be
Dom
Rene
R
Bex
Dorien
D
Salden
Ivo
I
Caeckebeke
Jo
J
Wibail
Alain
A
Borghgraef
Martine
M
Legius
Eric
E
Fryns
Jean-Pierre
JP
Matthijs
Gert
G
D000368:Aged; D000369:Aged, 80 and over; D001259:Ataxia / Q000235:genetics*; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009460:Neurologic Examination; D016601:RNA-Binding Proteins / Q000235:genetics*; D014202:Tremor / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human