SOMATIC EXPANSION OF THE (CAG)(N) REPEAT IN HUNTINGTON DISEASE BRAINS

The mutation causing Huntington disease (HD) has been identified as an expansion of a polymorphic (CAG)(n) repeat in the 5' part of the hunt ingtin gene. The specific neuropathology of HD, viz. selective neurona l loss in the caudate nucleus and putamen, cannot be explained by the widespread expression of the gene. Since somatic expansion is observed in affected tissue in myotonic dystrophy, we have studied the length of the (CAG)(n) repeat in various regions of the brain. Although we ha ve not found clear differences when comparing severely and mildly affe cted regions, we have observed a minor increase in repeat length upon comparison of affected brain samples with cerebellum or peripheral blo od. Hence, although further somatic amplification seems to occur in af fected areas of the brain, the differences between affected and unaffe cted regions are too small to make this mechanism an obvious candidate for the cause of differential neuronal degeneration in HD.