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Genetic variability of the retromer cargo recognition complex in parkinsonism
Author(s) -
Gustavsson Emil K.,
Guella Ilaria,
Trinh Joanne,
SzuTu Chelsea,
Rajput Alex,
Rajput Ali H.,
Steele John C.,
McKeown Martin,
Jeon Beom S.,
Aasly Jan O.,
Farrer Matthew J.
Publication year - 2015
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.26104
Subject(s) - retromer , parkinsonism , nonsynonymous substitution , genetics , biology , mutation , missense mutation , gene , disease , medicine , pathology , endosome , genome , intracellular
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). Conclusion 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. © 2014 International Parkinson and Movement Disorder Society