Neurological Phenotype in FMR1 Premutation Carriers

Project: Research project

Project Details


A newly identified neurological disorder, with progressive intention tremor, gait ataxia, and pronounced cognitive decline, has recently been identified in a substantial fraction of males over 50 years of age who have premutation alleles of the fragile X mental retardation 1 (FMR1) gene. Prior to the onset of tremor/ataxia, none of the affected males had any clinical evidence of involvement with fragile X syndrome (FXS). Moreover, FXS is not known to be associated with the same gene (FMR1) as FXS, it is likely to be a distinct disorder. Knowledge of the association between this neurological phenotype and the FMR1 gene will gave a significant impact on the diagnosis of tremor/ataxia within the aging population. In excess of 1 in 2,000 individuals may develop this disorder during their lifetime, which would make it one of the most common (known) single-gene cause of tremor/ataxia. An understanding of who among premutation carriers is likely to develop this disorder would serve both to direct counseling and to guide the development of preemptive therapies. To define the association between the neurological phenotype and the FMR1 gene, A multi-center study is proposed that will involve robust ascertainment of premutation carriers (55-200 CGG repeats) over the age of 50 years, and of both genders. Controls will be matched for age and gender, and will be drawn from the fragile X families. All subjects and controls will undergo a videotaped analysis of neurological function utilizing standard measures. Three experienced movement disorder specialists will evaluate the videotapes in a blinded fashion for the frequency an characteristics of the phenotype. Affected individuals will undergo a more thorough, direct neurological examination. The project will also include an analysis of association of the phenotype with a newly described molecular abnormality of the premutation range (elevated FMR1 mRNA).
Effective start/end date7/1/026/30/06


  • National Institutes of Health: $283,920.00
  • National Institutes of Health: $286,175.00
  • National Institutes of Health: $309,981.00
  • National Institutes of Health: $281,664.00


  • Medicine(all)
  • Neuroscience(all)


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