TRINUCLEOTIDE REPEAT LENGTH AND PROGRESSION OF ILLNESS IN HUNTINGTONS-DISEASE

The genetic defect causing Huntington's disease (HD) has been identifi ed as an unstable expansion of a trinucleotide (CAG) repeat sequence w ithin the coding region of the IT15 gene on chromosome 4. In 50 patien ts with manifest HD who were evaluated prospectively and uniformly, we examined the relationship between the extent of the DNA expansion and the rate of illness progression. Although the length of CAG repeats s howed a strong inverse correlation with the age at onset of HD, there was no such relationship between the number of CAG repeats and the rat e of clinical decline. These findings suggest that the CAG repeat leng th may influence or trigger the onset of HD, but other genetic, neurob iological, or environmental factors contribute to the progression of i llness and the underlying pace of neuronal degeneration.