Genetics of parkinsonism.
Ten years ago, alpha-synuclein mutations were discovered as the first genetic cause of Parkinson's disease (PD). In the following years, linkage mapping and positional cloning studies revealed further highly-penetrant (Mendelian) PD-causing mutations in the parkin, DJ-1, PINK1, LRRK2, and ATP13A2 genes, delineating a highly heterogeneous etiological scenario. Perhaps even more importantly, a low-penetrance LRRK2 mutation (Gly2019Ser) and polymorphic variants in alpha-synuclein and LRRK2 are emerging as relevant genetic determinants for sporadic PD in several populations. Other Mendelian genes remain to be found, but the complete resolution of the genetic architectures of the common PD forms represents the main challenge for the next decade.
Bonifati
Vincenzo
V
Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands. v.bonifati@erasmusmc.nl
D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000473:pathology; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D006180:Proton-Translocating ATPases / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D000099202:PTEN-Induced Putative Kinase
D047908:Intracellular Signaling Peptides and Proteins; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D006180:Proton-Translocating ATPases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C514983:ATP13A2 protein, human; C111567:parkin protein; C495280:LRRK2 protein, human; C105131:PARK7 protein, human