1. The fragile X tremor ataxia syndrome in the differential diagnosis of multiple system atrophy: data from the EMSA Study Group.
- Author
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Kamm C, Healy DG, Quinn NP, Wüllner U, Moller JC, Schols L, Geser F, Burk K, Børglum AD, Pellecchia MT, Tolosa E, del Sorbo F, Nilsson C, Bandmann O, Sharma M, Mayer P, Gasteiger M, Haworth A, Ozawa T, Lees AJ, Short J, Giunti P, Holinski-Feder E, Illig T, Wichmann HE, Wenning GK, Wood NW, and Gasser T
- Subjects
- Aged, Ataxia complications, Ataxia diagnosis, Cerebellar Ataxia complications, Cerebellar Ataxia diagnosis, Cerebellar Ataxia genetics, Cohort Studies, Diagnosis, Differential, Female, Fragile X Mental Retardation Protein, Fragile X Syndrome complications, Fragile X Syndrome diagnosis, Gene Frequency, Genotype, Humans, Male, Middle Aged, Multiple System Atrophy diagnosis, Mutation, Nerve Tissue Proteins genetics, Peripheral Nervous System Diseases complications, Peripheral Nervous System Diseases genetics, RNA-Binding Proteins genetics, Repetitive Sequences, Nucleic Acid genetics, Tremor complications, Tremor diagnosis, Ataxia genetics, Fragile X Syndrome genetics, Multiple System Atrophy genetics, Tremor genetics
- Abstract
The recent identification of fragile X-associated tremor ataxia syndrome (FXTAS) associated with premutations in the FMR1 gene and the possibility of clinical overlap with multiple system atrophy (MSA) has raised important questions, such as whether genetic testing for FXTAS should be performed routinely in MSA and whether positive cases might affect the specificity of current MSA diagnostic criteria. We genotyped 507 patients with clinically diagnosed or pathologically proven MSA for FMR1 repeat length. Among the 426 clinically diagnosed cases, we identified four patients carrying FMR1 premutations (0.94%). Within the subgroup of patients with probable MSA-C, three of 76 patients (3.95%) carried premutations. We identified no premutation carriers among 81 patients with pathologically proven MSA and only one carrier among 622 controls (0.16%). Our results suggest that, with proper application of current diagnostic criteria, FXTAS is very unlikely to be confused with MSA. However, slowly progressive disease or predominant tremor are useful red flags and should prompt the consideration of FXTAS. On the basis of our data, the EMSA Study Group does not recommend routine FMR1 genotyping in typical MSA patients.
- Published
- 2005
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