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).
| Leehey, Maureen A; Hagerman, Paul J (2012) Fragile X-associated tremor/ataxia syndrome. Handb Clin Neurol 103:373-86 |
| Hallahan, Brian P; Craig, Michael C; Toal, Fiona et al. (2011) In vivo brain anatomy of adult males with Fragile X syndrome: an MRI study. Neuroimage 54:16-24 |
| Garcia-Arocena, Dolores; Yang, Jane E; Brouwer, Judith R et al. (2010) Fibroblast phenotype in male carriers of FMR1 premutation alleles. Hum Mol Genet 19:299-312 |
| Zhang, L; Coffey, S; Lua, L L et al. (2009) FMR1 premutation in females diagnosed with multiple sclerosis. J Neurol Neurosurg Psychiatry 80:812-4 |
| Soontarapornchai, Kultida; Maselli, Ricardo; Fenton-Farrell, Grace et al. (2008) Abnormal nerve conduction features in fragile X premutation carriers. Arch Neurol 65:495-8 |
| Leehey, M A; Berry-Kravis, E; Goetz, C G et al. (2008) FMR1 CGG repeat length predicts motor dysfunction in premutation carriers. Neurology 70:1397-402 |
| Cornish, K; Turk, J; Hagerman, R (2008) The fragile X continuum: new advances and perspectives. J Intellect Disabil Res 52:469-82 |
| Amiri, Khaled; Hagerman, Randi J; Hagerman, Paul J (2008) Fragile X-associated tremor/ataxia syndrome: an aging face of the fragile X gene. Arch Neurol 65:19-25 |
| Grigsby, Jim; Brega, Angela G; Leehey, Maureen A et al. (2007) Impairment of executive cognitive functioning in males with fragile X-associated tremor/ataxia syndrome. Mov Disord 22:645-50 |
| Bourgeois, James A; Cogswell, Jennifer B; Hessl, David et al. (2007) Cognitive, anxiety and mood disorders in the fragile X-associated tremor/ataxia syndrome. Gen Hosp Psychiatry 29:349-56 |
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