Localization of the Gene for Rapidly Progressive Autosomal Dominant Parkinsonism and Dementia with Pallido-Ponto-Nigral Degeneration to Chromosome 17q21

Abstract

Rapidly progressive autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration (PPND) is a neurodegenerative disorder which begins later in life (>30 years of age) and is characterized by rapidly progressive parkinsonism, dystonia, dementia, perservative vocalizations and pyramidal tract dysfunction. The disease is observed in a large American family that includes almost 300 members in nine generations with 34 affected individuals. In this kindred evidence for linkage to chromosome 17q21 was obtained with a maximum lod score of 9.08 for the D17S958 locus. Multilocus analysis positions the disease gene in an ∼10 cM region between D17S250 and D17S943. Notably, the disease locus for a clinically distinct familial neurodegenerative disease named ‘disinhibition-dementia-parkinsonism-amyotrophy complex’ (DDPAC) was recently mapped to the same region of chromosome 17, suggesting that PPND and DDPAC may possibly originate from mutations in the same gene.