title: Genetic variability of the retromer cargo recognition complex in parkinsonism.
abstract: BACKGROUND
  A pathogenic mutation (VPS35 p.D620N) within the retromer complex has been shown to segregate with late-onset Parkinson's disease (PD). Several studies have subsequently detected the mutation in patients with PD and not in controls.
  
  
  METHODS
  Mutation screening of the coding regions of the retromer cargo recognition complex genes (VPS26A/B, VPS29, and VPS35) was carried out in patients with PD (n = 396), atypical parkinsonism (n = 229), and in 368 controls.
  
  
  RESULTS
  Overall, we identified five rare nonsynonymous mutations in VPS26A and one in VPS35; none were observed in VPS26B or VPS29. Three VPS26A variants (p.K93E, p.M112V, and p.K297X), identified in patients with atypical parkinsonism, were not observed in controls from this study (n = 368) or from publically available data sets (n = 4,426).
  
  
  CONCLUSIONS
  Our results support the hypothesis that rare variants in the retromer complex genes may be involved in the development of parkinsonism, although further studies are warranted before any solid conclusions can be drawn.
authors.affiliation: Djavad Mowafaghian Centre for Brain Health, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada; Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway; Department of Neurology, St. Olav's Hospital, Trondheim, Norway.
authors.forename: Emil K
authors.initials: EK
authors.lastname: Gustavsson
authors.forename: Ilaria
authors.initials: I
authors.lastname: Guella
authors.forename: Joanne
authors.initials: J
authors.lastname: Trinh
authors.forename: Chelsea
authors.initials: C
authors.lastname: Szu-Tu
authors.forename: Alex
authors.initials: A
authors.lastname: Rajput
authors.forename: Ali H
authors.initials: AH
authors.lastname: Rajput
authors.forename: John C
authors.initials: JC
authors.lastname: Steele
authors.forename: Martin
authors.initials: M
authors.lastname: McKeown
authors.forename: Beom S
authors.initials: BS
authors.lastname: Jeon
authors.forename: Jan O
authors.initials: JO
authors.lastname: Aasly
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000235:genetics*; D033921:Vesicular Transport Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D033921:Vesicular Transport Proteins
keywords: NGS; VPS26 VPS29 VPS35; mutation screening; parkinsonism; retromer complex