FMR1 premutations associated with fragile X-associated tremor/ataxia syndrome in multiple system atrophy.
BACKGROUND
Fragile X-associated tremor/ataxia syndrome (FXTAS), a novel disorder in male carriers of premutations of the fragile X mental retardation 1 gene (FMR1), was recently described. The clinical presentation of FXTAS most closely resembles multiple system atrophy (MSA) because both disorders manifest with cerebellar ataxia, intention tremor, autonomic dysfunction, and parkinsonism. It has been proposed that FXTAS might be a common neurodegenerative disorder.


OBJECTIVE
To determine whether FXTAS accounts for patients currently diagnosed as having MSA or a related clinical diagnosis.


METHODS
Patients with MSA or related phenotypes were examined by experienced movement disorders neurologists, and DNA samples were obtained for genetic study.


METHODS
Salpêtrière Hospital.


METHODS
Seventy-seven patients clinically diagnosed as having MSA, 19 as having olivopontocerebellar atrophy, and 27 as having cerebellar ataxia.


METHODS
The number of FMR1 repeats was determined in all patients by polymerase chain reaction. Alleles above 40 CGG repeats were controlled by Southern blot analysis.


RESULTS
Two patients carried FMR1 premutations of 110 and 135 repeats: a man with a familial form of cerebellar ataxia and a woman diagnosed as having MSA-cerebellar type. In addition, 9 patients (7%) carried alleles in the intermediate size range, from 41 to 53 repeats.


CONCLUSIONS
We confirm the recent initial description of FXTAS in women. Our data suggest that FXTAS is rare in MSA and indicate that FXTAS might be less prevalent than proposed.
Biancalana
Valérie
V
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasburg, France.
Toft
Mathias
M
Le Ber
Isabelle
I
Tison
François
F
Scherrer
Elisabeth
E
Thibodeau
Stephen
S
Mandel
Jean Louis
JL
Brice
Alexis
A
Farrer
Matthew J
MJ
Dürr
Alexandra
A
D000328:Adult; D000368:Aged; D000483:Alleles; D002524:Cerebellar Ataxia / Q000150:complications / Q000235:genetics*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000150:complications / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009849:Olivopontocerebellar Atrophies / Q000150:complications / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D014202:Tremor / Q000150:complications / Q000235:genetics*
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human