Trinucleotide repeats: Mechanisms and pathophysiology

Within the closing decade of the twentieth century, 14 neurological disorde rs were shown to result from the expansion of unstable trinucleotide repeat s, establishing this once unique mutational mechanism as the basis of an ex panding class of diseases. Trinucleotide repeat diseases can be categorized into two subclasses based on the location of the trinucleotide repeats: di seases involving noncoding repeats (untranslated sequences) and diseases in volving repeats within coding sequences (exonic). The large body of knowled ge accumulating in this fast moving field has provided exciting clues and i nspired many unresolved questions about the pathogenesis of diseases caused by expanded trinucleotide repeats. This review summarizes the current unde rstanding of the molecular pathology of each of these diseases, starting wi th a clinical picture followed by a focused description of the disease gene s, the proteins involved, and the studies that have lent insight into their pathophysiology.