TRINUCLEOTIDE REPEAT LENGTH AND CLINICAL PROGRESSION IN HUNTINGTONS-DISEASE

We examined the relationship between length of the trinucleotide (CAG) repeat at IT-15 and clinical progression of Huntington's disease in 4 6 mildly to moderately affected patients over a 2-year interval. Patie nts were divided into those with short mutations (37 to 46 repeats; n = 25) and those with long mutations (greater than or equal to 47 repea ts; n = 21). Patients with long repeat lengths had earlier age at onse t and were younger and less functionally impaired than those with shor t repeats at the initial visit, but the groups did not differ in sever ity of neurologic or cognitive impairment. However, the long-repeat gr oup displayed significantly greater decline in both neurologic and cog nitive functioning over the 2-year follow-up period. The length of the CAG repeat correlated highly with age at onset (r = -0.72, p < 0.001) and was a strong predictor of decline in both neurologic and cognitiv e function. The mechanism of gene action, and the means by which longe r expansions result in a more malignant disease process, remain to be elucidated.