Trinucleotide repeatlength andprogression of illness inHuntington's disease

Thegenetic defect causing Huntington's disease (HD)hasbeenidentified asan unstableexpansionof a trinucleotide (CAG)repeat sequence within thecoding region oftheIT15geneonchromosome4. In50patients withmanifest HD whowere evaluated prospectively anduniformly, we examined therelationship betweentheextentoftheDNA expansion andtherateof illness progression. Althoughthelength ofCAG repeats showeda stronginverse correlation withtheageatonsetofHD, there wasnosuchrelationship between the numberofCAG repeats andtherateof clinical decline. Thesefindings suggest thattheCAG repeat length mayinfluence ortrigger theonsetofHD,butothergenetic,neurobiological, or environmental factors contribute totheprogression of illness andtheunderlying paceofneuronal degeneration.