Summary
Today, a genetic contribution to the etiology of Parkinson’s disease (PD) is generally accepted, based on the demonstration of a familial aggregation of the disease, as demonstrated by several case-control and twin-studies. However, most cases ofPD appear to be sporadic, and in the majority of those with a positive family history, no clear mendelian mode of inheritance can be established. Therefore, a polygenic mode of inheritance or a multifactorial etiology is likely in these cases.
On the other hand, a number of families have been identified, in whom parkinsonism is inherited as an apparently monogenic mendelian trait with high penetrance. In several of these families, the disease genes have been mapped and mutations have been identified in some of them. The first gene locus has been mapped to the long arm of chromosome 4 in a small number of families with autosomal-dominant inheritance and typical Lewy-body pathology (PARK 1), and mutations have been identified in the gene for α-synuclein in these kindreds. Two other loci in families with dominant inheritance have been mapped, to chromosome 2p13 (PARK 3) and to chromosome 4p, respectively. A gene causing autosomal recessive parkinsonism of juvenile onset has been mapped to chromosome 6 (PARK 2), and the causative gene has been identified and named parkin.
Each of these genetically defined familial disorders share clinical characteristics that fulfill the criteria accepted for idiopathic Parkinson’s disease but, as in sporadic PD, also show a variability of clinical expressions, both within and between families. At present, there is no direct 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 also on the molecular pathogenesis of the common sporadic form of this disorder.
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Gasser, T. (2000). Autosomal-dominantly inherited forms of Parkinson’s disease. In: Mizuno, Y., Calne, D.B., Horowski, R., Poewe, W., Riederer, P., Youdim, M.B.H. (eds) Advances in Research on Neurodegeneration. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6284-2_3
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