GENETICS OF PARKINSONS-DISEASE

A genetic contribution to the etiology of Parkinson's disease (PD) is now well established, based on the demonstration of a familial aggrega tion of the disease as demonstrated by several case-control and twin s tudies, and on the description of large multigenerational families, in whom PD is inherited in a Mendelian fashion. In a few families with a utosomal dominant inheritance and typical Lewy-body pathology, a gene locus has been mapped to the long arm of chromosome 4, and mutations h ave been identified in the gene for alpha-synuclein. A gene causing au tosomal recessive parkinsonism of juvenile onset has been mapped to ch romosome 6, and the causative gene has been identified and named Parki n. This form of parkinsonism differs pathologically from the sporadic disease, as no Lewy bodies are found in the substantia nigra. A third locus, again in families with dominant inheritance, typical Lewy-body pathology and late onset, has been mapped to chromosome 2p13. At prese nt,. there is no evidence that any of these genes for familial Parkins onian syndromes have a direct role in the etiology of the common spora dic form of PD. However, the elucidation of the molecular sequence of events leading to nigral degeneration in these inherited cases is like ly to shed light on the molecular pathogenesis of this common neurodeg enerative disorder.