THE LIKELIHOOD OF BEING AFFECTED WITH HUNTINGTON-DISEASE BY A PARTICULAR AGE, FOR A SPECIFIC CAG SIZE

Prior studies describing the relationship between CAG size and the age at onset of Huntington disease (HD) have focused on affected persons. To further define the relationship between CAG repeat size and age at onset of HD, we now have analyzed a large cohort of affected and asym ptomatic at-risk persons with CAG expansion. This cohort numbered 1,04 9 persons, including 321 at-risk and 728 affected individuals with a C AG size of 29-121 repeats. Kaplan-Meier analysis has provided curves f or determining the likelihood of onset at a given age, for each CAG re peat length in the 39-50 range. The curves were significantly differen t (P < .0005), with relatively narrow 95% confidence intervals (95% CI ) (+/-10%). Penetrance of the mutation for HD also was examined. Altho ugh complete penetrance of HD was observed for CAG sizes of greater th an or equal to 42, only a proportion of those with a CAG repeat length of 36-41 showed signs or symptoms of HD within a normal life span. Th ese data provide information concerning the likelihood of being affect ed, by a specific age, with a particular CAG size, and they may be use ful in predictive-testing programs and for the design of clinical tria ls for persons at increased risk for HD.