A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants.
BMJ Publishing Group, 2012
Online
academicJournal
Zugriff:
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.
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A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants.
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Autor/in / Beteiligte Person: | 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, Gaëtan ; Gispert, Suzana ; Auburger, Georg ; Vilarino-Guell, 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, Cécile ; 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 ; Kruger, Rejko |
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Veröffentlichung: | BMJ Publishing Group, 2012 |
Medientyp: | academicJournal |
DOI: | 10.1136/jmedgenet-2012-101155 |
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