FMR1 premutations associated with fragile X-associated tremor/ataxia syndrome in multiple system atrophy

Valérie Biancalana, Mathias Toft, Isabelle Le Ber, François Tison, Elisabeth Scherrer, Stephen N Thibodeau, Jean Louis Mandel, Alexis Brice, Matthew J. Farrer, Alexandra Dürr

Research output: Contribution to journalArticle

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Abstract

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. Design: Patients with MSA or related phenotypes were examined by experienced movement disorders neurologists, and DNA samples were obtained for genetic study. Setting: Salpêtrière Hospital. Patients: Seventy-seven patients clinically diagnosed as having MSA, 19 as having olivopontocerebellar atrophy, and 27 as having cerebellar ataxia. Main Outcome Measure: 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.

Original languageEnglish (US)
Pages (from-to)962-966
Number of pages5
JournalArchives of Neurology
Volume62
Issue number6
DOIs
StatePublished - Jun 2005

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Multiple System Atrophy
Intellectual Disability
Cerebellar Ataxia
Genes
Olivopontocerebellar Atrophies
Alleles
Movement Disorders
Parkinsonian Disorders
Tremor
Southern Blotting
Fragile X Tremor Ataxia Syndrome
Syndrome
Mental Retardation
Gene
Neurodegenerative Diseases
Outcome Assessment (Health Care)
Phenotype
Polymerase Chain Reaction
Repeats
DNA

ASJC Scopus subject areas

  • Neuroscience(all)

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FMR1 premutations associated with fragile X-associated tremor/ataxia syndrome in multiple system atrophy. / Biancalana, Valérie; Toft, Mathias; Le Ber, Isabelle; Tison, François; Scherrer, Elisabeth; Thibodeau, Stephen N; Mandel, Jean Louis; Brice, Alexis; Farrer, Matthew J.; Dürr, Alexandra.

In: Archives of Neurology, Vol. 62, No. 6, 06.2005, p. 962-966.

Research output: Contribution to journalArticle

Biancalana, V, Toft, M, Le Ber, I, Tison, F, Scherrer, E, Thibodeau, SN, Mandel, JL, Brice, A, Farrer, MJ & Dürr, A 2005, 'FMR1 premutations associated with fragile X-associated tremor/ataxia syndrome in multiple system atrophy', Archives of Neurology, vol. 62, no. 6, pp. 962-966. https://doi.org/10.1001/archneur.62.6.962
Biancalana, Valérie ; Toft, Mathias ; Le Ber, Isabelle ; Tison, François ; Scherrer, Elisabeth ; Thibodeau, Stephen N ; Mandel, Jean Louis ; Brice, Alexis ; Farrer, Matthew J. ; Dürr, Alexandra. / FMR1 premutations associated with fragile X-associated tremor/ataxia syndrome in multiple system atrophy. In: Archives of Neurology. 2005 ; Vol. 62, No. 6. pp. 962-966.
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AU - Scherrer, Elisabeth

AU - Thibodeau, Stephen N

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