title: Genetics of Parkinson's disease--state of the art, 2013.
abstract: In the past 15 years there has been substantial progress in our understanding of the genetics of Parkinson's disease (PD). Highly-penetrant mutations in different genes (SNCA, LRRK2, VPS35, Parkin, PINK1, and DJ-1) are known to cause rare monogenic forms of the disease. Furthermore, different variants with incomplete penetrance in the LRRK2 and the GBA gene are strong risk factors for PD, and are especially prevalent in some populations. Last, common variants of small effect size, modulating the risk for PD, have been identified by genome-wide association studies in more than 20 chromosomal loci. Here, I first outline the evolution of the research strategies to find PD-related genes, and then focus on recent advances in the field of the monogenic forms, including VPS35 mutations in autosomal dominant PD, and DNAJC6 and SYNJ1 mutations in recessive forms of juvenile parkinsonism. Additional genetic determinants of PD likely remain to be identified, as the currently known mutations and variants only explain a minor fraction of the disease burden. There is great expectation that the new DNA sequencing technologies (exome and whole-genome sequencing) will bring us closer to the full resolution of the genetic landscape of PD.
authors.affiliation: Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands. Electronic address: v.bonifati@erasmusmc.nl.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bonifati
mesh_terms: D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D012307:Risk Factors; D033921:Vesicular Transport Proteins / Q000235:genetics; D000099182:Phosphoinositide 5-Phosphatases
chemical_list: D050956:HSP40 Heat-Shock Proteins; D010744:Phosphoric Monoester Hydrolases; D033921:Vesicular Transport Proteins; D000099182:Phosphoinositide 5-Phosphatases; C494652:DNAJC6 protein, human; C419573:VPS35 protein, human
keywords: ATP13A2; DJ-1; DNAJC6; FBXO7; Genetics; LRRK2; PINK1; PLA2G6; Parkin; Parkinson's disease; Parkinsonism; SNCA; SYNJ1; VPS35