DENTATORUBRAL AND PALLIDOLUYSIAN ATROPHY EXPANSION OF AN UNSTABLE CAGTRINUCLEOTIDE ON CHROMOSOME-12P

Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal domin ant neurodegenerative disorder characterized by combined systemic dege neration of the dentatofugal and pallidofugal pathways. We investigate d a candidate gene and found that DRPLA patients had an expanded CAG t rinucleotide repeat in a gene on the short arm of chromosome 12. The r epeat size varied from 7-23 in normal individuals. In patients one all ele was expanded to between 49-75 repeats or occasionally even more. E xpansion was usually associated with paternal transmission and only oc casionally with maternal transmission. Repeat size showed a close corr elation with age of onset of symptoms and disease severity. We conclud e that DRPLA is the seventh genetic disorder known to be associated wi th expansion of an unstable trinucleotide repeat.