title: Update on genetics of parkinsonism.
abstract: BACKGROUND
  Major progress in genetic studies of Parkinson's disease (PD) and parkinsonism has been achieved in the last two decades.
  
  
  OBJECTIVE
  We provide a brief review of the current status of PARK and non-PARK loci/genes, and discuss two new genes: eIF4G1 and VPS35.
  
  
  METHODS
  The literature on PARK and non-PARK loci/genes was reviewed and some novel information on two new genes is provided.
  
  
  RESULTS
  There are 18 PARK loci. The symptomatic carriers of these genes usually present with parkinsonism, although additional clinical features can be seen during the course of the disease. Carriers of non-PARK loci/genes frequently present with a mixed phenotype that includes parkinsonism and additional clinical features. Carriers of the eIF4G1 and VPS35 genes present with a parkinsonian phenotype. The pathology of eIF4G1 is of the α-synuclein type; the pathology of VPS35 is unknown.
  
  
  CONCLUSIONS
  The current genetic classification of PD/parkinsonism genes is not ideal. The pathological classification based on the accumulation of particular proteins/inclusions is also misleading since there are kindred with a single mutation but pleomorphic pathology. A better classification of neurodegenerative conditions is needed. It is hoped that the genetic studies will lead to better therapies.
authors.affiliation: Department of Neurology, Mayo Clinic Florida, Jacksonville, Fla 32224, USA.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Fujioka
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
mesh_terms: D039603:Eukaryotic Initiation Factor-4G / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000235:genetics*; D033921:Vesicular Transport Proteins / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: C113920:EIF4G1 protein, human; D039603:Eukaryotic Initiation Factor-4G; C419573:VPS35 protein, human; D033921:Vesicular Transport Proteins; D051844:alpha-Synuclein