title: Clinical implications of gene discovery in Parkinson's disease and parkinsonism.
abstract: Over the past decade, major progress has been achieved in the identification of genes associated with Parkinson's disease (PD) and parkinsonism. Five genes have now been shown conclusively to play a role in PD susceptibility. Mutations in three of these genes, PRKN, PINK1, and DJ1, are important in early onset, recessively inherited PD, while mutations in LRRK2 and SNCA result in autosomal-dominant PD. LRRK2 has emerged as the most prevalent genetic cause of PD and has been implicated in both familial and sporadic forms of disease. In addition, autosomal-dominant dementia and Parkinsonism has been shown to be caused by mutations in the MAPT and PGRN genes. Molecular tests are now commercially available for several of these genes; however, in some of them, positive results need to be interpreted with caution until penetrance is better understood. In addition, clinical treatment of PD remains largely unaltered by the results of genetic testing.
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, Florida 32224, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Wider
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
mesh_terms: D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D009154:Mutation / Q000235:genetics; D018696:Neuroprotective Agents / Q000627:therapeutic use; D015513:Oncogene Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000235:genetics*; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics; D016875:tau Proteins / Q000235:genetics; D000099202:PTEN-Induced Putative Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D018696:Neuroprotective Agents; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D051844:alpha-Synuclein; D016875:tau Proteins; D000099202:PTEN-Induced Putative Kinase; C054369:MAPT protein, human; C497604:SNCA protein, human; C495280:LRRK2 protein, human; C105131:PARK7 protein, human