THE MOLECULAR-GENETICS OF HUNTINGTONS-DISEASE

The past year has witnessed outstanding developments in research on Hu ntington's disease (HD). A gene was identified that contains an expand ed CAG trinucleotide repeat on HD chromosomes. Patterns of expression of this gene and the nature of two transcripts were identified. CAG re peat size ranges between 36 and 121 in affected persons, and it is a h ighly sensitive and specific marker for HD. A correlation between CAG repeat size and the age of onset of HD was demonstrated. Identificatio n of this mutation has facilitated direct approaches to predictive tes ting for HD. The new mutation rate, previously deemed to be exceedingl y rare, is now shown to be responsible for up to 3% of affected person s. Although the mechanism by which CAG repeat length induces neuronal death is not known, there is evidence that the pathogenesis involves a gain of function in the HD gene.