Genetic aspect of Parkinson's disease.

Introduction. - What is the role of genetic factors in the pathophysiology of idiopathic Parkinson's disease, one of the most frequent neurodegenerati ve disorders? In the past two years, identification of two genes and locali zation of a third one have supported the hypothesis that genetics factors a re involved in idiopathic Parkinson's disease. We present arguments that su pport such hypothesis, and describe recent advances in genetic studies of i diopathic Parkinson's disease. Current knowledge and key points. - The first gene identified on chromosome 4 encodes alpha-synuclein, It causes a rare form of autosomal dominant Par kinson's disease. A locus on the short arm of chromosome 2 was recently ide ntified in families with autosomal dominant Parkinson's disease. More recen tly, the gene encoding Parkin (located on chromosome 6) has been described. It already appears to be an important locus for juvenile parkinsonism with autosomal recessive transmission. Conclusion. - We now have to understand how mutations in these genes lead t o selective degeneration of dopaminergic neurons, and to determine whether or not they participate in the genetic susceptibility of idiopathic Parkins on's disease. (C) 1999 Elsevier, Paris.