TheLikelihood ofBeing Affected withHuntington Disease bya Particular Age,fora Specific CAG Size

Summary Prior studies describing therelationship between CAG size andtheageatonset ofHuntington disease (HD) havefocused onaffected persons. Tofurther define the relationship between CAGrepeat size andageatonset ofHD,wenowhaveanalyzed alarge cohort ofaffected andasymptomatic at-risk persons withCAGexpansion. Thiscohort numbered 1,049 persons, including 321atrisk and728affected individuals withaCAGsize of 29-121repeats. Kaplan-Meier analysis hasprovided curves fordetermining thelikelihood ofonset atagiven age, foreachCAGrepeat length inthe39-50range. Thecurves weresignificantly different (P<.0005), with relatively narrow 95%confidence intervals (95%GI) (±10%). Penetrance ofthemutation forHD also was examined. Although complete penetrance ofHD was observed forCAGsizes of-42,onlyaproportion of those with aCAGrepeat length of36-41showed signs orsymptoms ofHD within anormal life span. These dataprovide information concerning thelikelihood of being affected, byaspecific age, withaparticular CAG size, andthey maybeuseful inpredictive-testi ng programs andforthedesign ofclinical trials forpersons at increased risk forHD.