Parkinson Disease Mutation Database





Parkinson disease

Note! This is a brief overview of the molecular genetics of Parkinson disease. Detailed information for lay persons, caregivers, physicians and researchers can be found on the web sites listed in the Links Section.

Parkinson disease (PD, OMIM entry 168600) is the most common neurodegenerative movement disorder and the second most common neurodegenerative brain disease after Alzheimers disease. In approximately 15% of PD patients a positive family history is reported, implying a genetic involvement in PD development. PD can segregate both as an autosomal dominant trait as well as an autosomal recessive trait in families. In these families, 5 genes are identified for which evidence is consistent that, when mutated, these cause PD. The α-synuclein gene (SNCA) and the leucine-rich repeat kinase 2 gene (LRRK2) were found to be linked to families with autosomal dominant inheritance, where as the parkin gene (PARK2), the PTEN-induced putative kinase 1 gene (PINK1) and the DJ-1 gene (PARK7) were identified by linkage studies in autosomal recessive families. Together, mutations in these genes are responsible for 10 to 15% of PD in general, with PARK2 mutations explaining up to 50% of familial PD cases. It is important to note that mutation frequencies in some of these genes are highly dependent on ethnicity. Although mutations in the known genes are a relatively rare cause of PD, they are important for presymptomatic diagnostics of patients in PD families that segregate these mutations. Also, the identification of these genes and mutations has been extremely important to the recent progress in the understanding of the biology of PD. In cases where the inheritance pattern is unclear and in sporadic cases other genetic factors may affect phenotypic outcome or increase one’s susceptibility to develop PD. These modifier and risk genes – as well as other causal genes - are also involved in PD and need to be identified to fully elucidate the etiology of PD. Ultimately, this will lead to the development of effective therapies for this major disease.

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