THE RELATIONSHIP BETWEEN TRINUCLEOTIDE (CAG) REPEAT LENGTH AND CLINICAL-FEATURES OF HUNTINGTONS-DISEASE

Huntington's disease (HD) is associated with the expansion of a CAG tr inucleotide repeat in a novel gene. We have assessed 360 HD individual s from 259 unrelated families and found a highly significant correlati on (r = 0.70, p = 10(-7) between the age of onset and the repeat lengt h, which accounts for approximately 50% of the variation in the age of onset. Significant associations were also found between repeat length and age of death and onset of other clinical features. Sib pair and p arent-child analysis revealed that the CAG repeat demonstrates only mi ld instability. Affected HD siblings had significant correlations for trinucleotide expansion (r = 0.66, p < 0.001) which was not apparent f or affected parent-child pairs.