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.
Centre for Human Genetics, University Hospital Leuven, Leuven, Belgium. Hilde.Vanesch@med.kuleuven.ac.be
Hilde
H
Van Esch
Rene
R
Dom
Dorien
D
Bex
Ivo
I
Salden
Jo
J
Caeckebeke
Alain
A
Wibail
Martine
M
Borghgraef
Eric
E
Legius
Jean-Pierre
JP
Fryns
Gert
G
Matthijs
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