Genetic etiology of Parkinson disease associated with mutations in the **SNCA, PARK2, PINK1, PARK7,** and **LRRK2** genes: a mutation update
Van Broeckhoven, Christine
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
New York, N.Y.
Human mutation. - New York, N.Y.
, p. 763-780
University of Antwerp
To date, molecular genetic analyses have identified over 500 distinct DNA variants in five disease genes associated with familial Parkinson disease; a-synuclein (SNCA), parkin (PARK2), PTEN-induced putative kinase 1 (PINK1), DJ-1 (PARK7), and Leucinerich repeat kinase 2 (LRRK2). These genetic variants include 82% simple mutations and 18% copy number variations. Some mutation subtypes are likely underestimated because only few studies reported extensive mutation analyses of all five genes, by both exonic sequencing and dosage analyses. Here we present an update of all mutations published to date in the literature, systematically organized in a novel mutation database (http://www.molgen.ua.ac.be/PDmutDB). In addition, we address the biological relevance of putative pathogenic mutations. This review emphasizes the need for comprehensive genetic screening of Parkinson patients followed by an insightful study of the functional relevance of observed genetic variants. Moreover, while capturing existing data from the literature it became apparent that several of the five Parkinson genes were also contributing to the genetic etiology of other Lewy Body Diseases and Parkinson-plus syndromes, indicating that mutation screening is recommendable in these patient groups.