TRINUCLEOTIDE REPEAT LENGTH INSTABILITY AND AGE-OF-ONSET IN HUNTINGTONS-DISEASE

The initial observation of an expanded and unstable trinucleotide repe at in the Huntington's disease gene has now been confirmed and extende d in 150 independent Huntington's disease families. HD chromosomes con tained 37-86 repeat units, whereas normal chromosomes displayed 11-34 repeats. The HD repeat length was inversely correlated with the age of onset of the disorder. The HD repeat was unstable in more than 80% of meiotic transmissions showing both increases and decreases in size wi th the largest increases occurring in paternal transmissions. The targ eting of spermatogenesis as a particular source of repeat instability is reflected in the repeat distribution of HD sperm DNA. The analysis of the length and instability of individual repeats in members of thes e families has profound implications for presymptomatic diagnosis.