TY - JOUR T1 - A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants JF - Journal of Medical Genetics JO - J Med Genet SP - 721 LP - 726 DO - 10.1136/jmedgenet-2012-101155 VL - 49 IS - 11 AU - Manu Sharma AU - John P A Ioannidis AU - Jan O Aasly AU - Grazia Annesi AU - Alexis Brice AU - Lars Bertram AU - Maria Bozi AU - Maria Barcikowska AU - David Crosiers AU - Carl E Clarke AU - Maurizio F Facheris AU - Matthew Farrer AU - Gaetan Garraux AU - Suzana Gispert AU - Georg Auburger AU - Carles Vilariño-Güell AU - Georgios M Hadjigeorgiou AU - Andrew A Hicks AU - Nobutaka Hattori AU - Beom S Jeon AU - Zygmunt Jamrozik AU - Anna Krygowska-Wajs AU - Suzanne Lesage AU - Christina M Lill AU - Juei-Jueng Lin AU - Timothy Lynch AU - Peter Lichtner AU - Anthony E Lang AU - Cecile Libioulle AU - Miho Murata AU - Vincent Mok AU - Barbara Jasinska-Myga AU - George D Mellick AU - Karen E Morrison AU - Thomas Meitnger AU - Alexander Zimprich AU - Grzegorz Opala AU - Peter P Pramstaller AU - Irene Pichler AU - Sung Sup Park AU - Aldo Quattrone AU - Ekaterina Rogaeva AU - Owen A. Ross AU - Leonidas Stefanis AU - Joanne D Stockton AU - Wataru Satake AU - Peter A Silburn AU - Tim M Strom AU - Jessie Theuns AU - Eng- King Tan AU - Tatsushi Toda AU - Hiroyuki Tomiyama AU - Ryan J Uitti AU - Christine Van Broeckhoven AU - Karin Wirdefeldt AU - Zbigniew Wszolek AU - Georgia Xiromerisiou AU - Harumi S Yomono AU - Kuo-Chu Yueh AU - Yi Zhao AU - Thomas Gasser AU - Demetrius Maraganore AU - Rejko Krüger AU - on behalf of GEOPD consortium Y1 - 2012/11/01 UR - http://jmg.bmj.com/content/49/11/721.abstract N2 - Background Two recent studies identified a mutation (p.Asp620Asn) in the vacuolar protein sorting 35 gene as a cause for an autosomal dominant form of Parkinson disease . Although additional missense variants were described, their pathogenic role yet remains inconclusive. Methods and results We performed the largest multi-center study to ascertain the frequency and pathogenicity of the reported vacuolar protein sorting 35 gene variants in more than 15,000 individuals worldwide. p.Asp620Asn was detected in 5 familial and 2 sporadic PD cases and not in healthy controls, p.Leu774Met in 6 cases and 1 control, p.Gly51Ser in 3 cases and 2 controls. Overall analyses did not reveal any significant increased risk for p.Leu774Met and p.Gly51Ser in our cohort. Conclusions Our study apart from identifying the p.Asp620Asn variant in familial cases also identified it in idiopathic Parkinson disease cases, and thus provides genetic evidence for a role of p.Asp620Asn in Parkinson disease in different populations worldwide. ER -