CAG REPEAT SIZE AND CLINICAL PRESENTATION IN HUNTINGTONS-DISEASE

The specific mutation in Huntington's disease (HD) is an expansion of the unstable CAG; trinucleotide repeat in the IT15 gene in chromosome 4p. We examined the relationship between the CAG repeat size and clini cal presentation in 36 patients with suspected diagnosis of HD. Twelve patients had no relatives with documented HD, and five of them failed to show the expanded (>37) CAG; repeats. The remaining 31 patients, i ncluding seven patients with atypical clinical features for HD (three without and four with family history of documented HD), were heterozyg otes for the CAG repeat expansion. There were large CAG repeats (50 co pies) in paternally transmitted HD cases with early onset (age 30 or e arlier). The rate of disease progression was faster in paternally tran smitted cases regard less of the CAG repeat length or age of onset. We conclude that (1) patients lacking the family history of HD frequentl y show no expansion of the CAG repeats, and (2) the sex of the affecte d parent influences both the CAG; repeat size and the phenotypic expre ssion of the HD gene in the offspring.