Genetics of Parkinson's disease.

A genetic contribution to the etiology of Parkinson's disease (PD) is now well established, based on the demonstration of a familial aggregation of the disease as demonstrated by several case control and twin studies, and on the description of large multigenerational families, in whom PD is inherited in a Mendelian fashion. In a few families with autosomal dominant inheritance and typical Lewy-body pathology, a gene locus has been mapped to the long arm of chromosome 4, and mutations have been identified in the gene for alpha-synuclein. A gene causing autosomal recessive parkinsonism of juvenile onset has been mapped to chromosome 6, and the causative gene has been identified and named Parkin. 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 2pl3. At present, there is no evidence that any of these genes for familial Parkinsonian syndromes have a direct role in the etiology of the common sporadic form of PD. However, the elucidation of the molecular sequence of events leading to nigral degeneration in these inherited cases is likely to shed light on the molecular pathogenesis of this common neurodegenerative disorder.