Hagerman, Paul — Biological Chemistry

We have recently identified a hitherto undescribed neurological disorder among male carriers of mutations in the fragile X gene. Mutations in this gene (expansions of a CGG repeat) are normally responsible for fragile X syndrome, the leading heritable form of mental retardation. However, carriers of smaller expansions were thought to be spared from any clinical involvement. We have found that some older male carriers develop neurological symptoms that may appear initially to be Parkinson‚s disease, but which may also involve tremulousness (e.g., difficulty with writing or eating), and balance problems (e.g., frequent falling). We are currently trying to determine both the nature and the extent of these problems among the carriers, and within the general population. The current project involves three centers, Chicago, Denver and Davis, and will better define the association between the neurological condition and the fragile X gene. This neurological syndrome may turn out to be one of the more common single-gene causes of dementia and of tremor. Thus, this investigation may have a significant impact on the diagnosis of tremor as well as dementia within the aging population.