Baylor Fragile X Research Center - Supplement

Baylor College Of Medicine, Houston TX

Investigators

Linked publications, trials & patents

Abstract

[unreadable] DESCRIPTION (provided by applicant): The fragile X syndrome (FXS), a type of inherited mental retardation, is due to the silencing of the FMR1 X-linked gene. In over 98% of cases, the mutation is due to the expansion of an unstable CGG repeat sequence located in the 5' untranslated region (UTR) of the gene. Once expanded to over 200 repeats, the FMR1 gene is hypermethylated and consequently no message is transcribed and no protein (FMRP) produced. Until recently, the unmethylated long CGG repeat track found in premutation carriers (60-200 repeats) was thought to have little phenotype consequence. The original goal of this study was to substantiate reports of an association between premutation male carriers and a late-onset neurodegenerative disorder resulting in action tremors - this has been accomplished through this project and others. This syndrome, now referred to as fragile X-associated tremor/ataxia syndrome (FXTAS), has a variable age at onset and progression. The principal investigator's focus now is to characterize the natural history of the syndrome and to identify risk factors associated with expression and severity. She will delineate the FMR1-related molecular correlates that best predict the risk for FXTAS among premutation males and females. Identification of such risk factors will provide clues for the underlying molecular etiology. In the last two years of the study, the investigator has gained significant experience with this syndrome and the issues related to recruiting participants. The investigator has an established infrastructure and study protocol to identify families with FXS, and to systematically ascertain all individuals in a sibship with a premutation carrier. The investigator's test battery to assess an individual's tremor/ataxia phenotype is unique, as she has instrumentation that objectively quantifies outcome measures. However, she has come upon several roadblocks that she did not anticipate with this study, and has requested a supplement to enhance the value of this study. First, the investigator requests funds to cover travel costs to expand her study population. She finds it necessary to travel to a participant's home to conduct the phenotype assessments due to their limitations. Second, imaging studies are essential to better characterize FXTAS and provide diagnostic criteria to the neurology community. Thirdly, the investigator is in great need of a genetic counselor to provide results and discuss FXTAS with family members. The older men in the families with FXS typically have not come to clinics with their grandsons who have FXS - they do not understand inheritance of this disorder and certainly had no idea that they may be at risk for a neurodegenerative disorder. Thus it is essential to have a genetic counselor associated with the study and one who will identify counseling issues specific to FXTAS and establish guidelines for others in this situation. With these additional funds, the results of this project will be immediately translatable to the medical community. [unreadable] [unreadable]