Genetics of Parkinsonʹs disease

Here we review familial Parkinsonʹs disease from clinical, as well as molecular genetic aspects. To date, two genes responsible for familial Parkinsonʹs disease have been identified: one is the α-synuclein gene located in the long arm of chromosome 4, and the other is the parkin gene located in the long arm of chromosome 6. The mode of inheritance of the former is autosomal dominant and clinical features consist of levodopa-responsive parkinsonism; the age of onset is younger than that of the sporadic cases (in their 40s), and the progression is faster (average disease duration approximately nine years). The latter form is transmitted as an autosomal recessive, and clinical features consist of early onset (in their 20s), levodopa-responsive parkinsonism, and a slow progression of the disease. In addition, the tau gene has been shown to be the disease gene for familial frontotemporal dementia and parkinsonism linked to chromosome 17. There are many other clinical phenotypes of familial Parkinsonʹs disease among which three forms have been mapped to certain chromosome loci: one is in the short arm of chromosome 2, the two other forms are in the different loci of the short arm of chromsome 4. All of them are transmitted as autosomal dominant traits manifesting levodopa responsive parkinsonism. There still exists however, other clinical phenotypes of chromosome loci which are not known. Molecular cloning of these familial Parkinsonʹs disease genes and the elucidation of the functions of the proteins encoded will certainly contribute greatly to the investigation of the etiology and pathogenesis of more common sporadic form of Parkinsonʹs disease.