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Neurological Phenotype in FMR1 Premutation Carriers


Funded by:  National Institute of Neurological Disorders and Stroke, National Institutes of Health
Project Period: July 2002 - June 2006

The objectives of the study are threefold: (1) to determine the prevalence of fragile X-associated tremor/ataxia syndrome (FXTAS) among male and female carriers of the fragile X premutation; (2) to define those features of the disorder that are associated with the fragile x mental retardation 1 (FMR1) gene, including the progressive nature of the disorder and gender-specific effects; and (3) to examine the relationship between symptom severity and a known molecular abnormality in premutation carriers (i.e., elevated FMR1 mRNA levels).

Two groups of individuals over the age of 50 will participate in the study: (1) men and women who are carriers of the fragile X premutation and (2) healthy men and women who do not have the premutation, but who have family members affected by fragile X. (Approximately 1000 individuals will be enrolled in the study, across three sites.) Each participant will undergo a single two-hour evaluation that includes a videotaped neurologic exam, neuropsychological testing, an assessment of functional ability, and genetic testing. Participants with FXTAS also will undergo a thorough neurological examination conducted by a neurologist specializing in movement disorders.

The study is based at the University of California at Davis, but participants also are being recruited at the University of Colorado Denver in Denver, Colorado, and Rush-Presbyterian-St. Luke's Medical Center in Chicago, Illinois.

Potential Impact of the Research
The knowledge gained as a result of this study will have a significant impact on the diagnosis of tremor and ataxia in the aging population. If all carriers of the fragile X premutation were to develop FXTAS, this newly identified disorder would be one of the most common known causes of tremor and ataxia. An understanding of who among premutation carriers is likely to develop this disorder will serve to direct counseling and guide the development of therapeutic approaches tailored to the treatment of FXTAS.

Project Staff
Principal Investigator of the Study:  Paul J. Hagerman, MD, PhD
Co-Principal Investigator at the University of Colorado Denver:  Maureen A. Leehey, MD
Co-Principal Investigator at Rush-Presbyterian-St. Luke's Medical Center:   Elizabeth Berry-Kravis, MD, PhD

Contact Information
For further information about this study, please contact Paul J. Hagerman by e-mail at