A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants. Issue 11 (2nd November 2012)

• Record Type: Journal Article
• Authors: Sharma, Manu; Ioannidis, John P A; Aasly, Jan O; Annesi, Grazia; Brice, Alexis; Bertram, Lars; Bozi, Maria; Barcikowska, Maria; Crosiers, David; Clarke, Carl E; Facheris, Maurizio F; Farrer, Matthew; Garraux, Gaetan; Gispert, Suzana; Auburger, Georg; Vilariño-Güell, Carles; Hadjigeorgiou, Georgios M; Hicks, Andrew A; Hattori, Nobutaka; Jeon, Beom S; Jamrozik, Zygmunt; Krygowska-Wajs, Anna; Lesage, Suzanne; Lill, Christina M; Lin, Juei-Jueng; Lynch, Timothy; Lichtner, Peter; Lang, Anthony E; Libioulle, Cecile; Murata, Miho; Mok, Vincent; Jasinska-Myga, Barbara; Mellick, George D; Morrison, Karen E; Meitnger, Thomas; Zimprich, Alexander; Opala, Grzegorz; Pramstaller, Peter P; Pichler, Irene; Park, Sung Sup; Quattrone, Aldo; Rogaeva, Ekaterina; Ross, Owen A.; Stefanis, Leonidas; Stockton, Joanne D; Satake, Wataru; Silburn, Peter A; Strom, Tim M; Theuns, Jessie; Tan, Eng- King; Toda, Tatsushi; Tomiyama, Hiroyuki; Uitti, Ryan J; Van Broeckhoven, Christine; Wirdefeldt, Karin; Wszolek, Zbigniew; Xiromerisiou, Georgia; Yomono, Harumi S; Yueh, Kuo-Chu; Zhao, Yi; Gasser, Thomas; Maraganore, Demetrius; Krüger, Rejko;
• Is Part Of: Journal of medical genetics. Volume 49:Issue 11(2012)
• Page Start: 721
• Page End: 726
• Publication Date: 2012-11-02
• Subjects: Parkinson-s disease -- Genome-wide -- Genetics -- Genetic epidemiology -- Complex traits; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2012-101155
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : 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.