Causal relation between alpha-synuclein gene duplication and familial Parkinson's disease.

The alpha-synuclein gene (SNCA) has been implicated in autosomal dominant forms of Parkinson's disease. We screened 119 individuals from families with this rare form of the disease for SNCA duplications by semiquantitative multiplex PCR. Two patients had duplications, which were confirmed by analysis of intragenic and flanking microsatellite markers. The phenotype in both patients was indistinguishable from idiopathic Parkinson's disease and no atypical features were present, by contrast with reports of families with triplication of the same gene. These results indicate that SNCA is more frequently associated with familial Parkinson's disease than previously thought, and that there is a clear dosage effect according to the number of supernumerary copies of this gene.