TY - JOUR
TI - A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants
AU - Sharma, M.
AU - Ioannidis, J.P.A.
AU - Aasly, J.O.
AU - Annesi, G.
AU - Brice, A.
AU - Bertram, L.
AU - Bozi, M.
AU - Barcikowska, M.
AU - Crosiers, D.
AU - Clarke, C.E.
AU - Facheris, M.F.
AU - Farrer, M.
AU - Garraux, G.
AU - Gispert, S.
AU - Auburger, G.
AU - Vilariño-Güell, C.
AU - Hadjigeorgiou, G.M.
AU - Hicks, A.A.
AU - Hattori, N.
AU - Jeon, B.S.
AU - Jamrozik, Z.
AU - Krygowska-Wajs, A.
AU - Lesage, S.
AU - Lill, C.M.
AU - Lin, J.-J.
AU - Lynch, T.
AU - Lichtner, P.
AU - Lang, A.E.
AU - Libioulle, C.
AU - Murata, M.
AU - Mok, V.
AU - Jasinska-Myga, B.
AU - Mellick, G.D.
AU - Morrison, K.E.
AU - Meitnger, T.
AU - Zimprich, A.
AU - Opala, G.
AU - Pramstaller, P.P.
AU - Pichler, I.
AU - Park, S.S.
AU - Quattrone, A.
AU - Rogaeva, E.
AU - Ross, O.A.
AU - Stefanis, L.
AU - Stockton, J.D.
AU - Satake, W.
AU - Silburn, P.A.
AU - Strom, T.M.
AU - Theuns, J.
AU - Tan, E.K.
AU - Toda, T.
AU - Tomiyama, H.
AU - Uitti, R.J.
AU - Van Broeckhoven, C.
AU - Wirdefeldt, K.
AU - Wszolek, Z.
AU - Xiromerisiou, G.
AU - Yomono, H.S.
AU - Yueh, K.-C.
AU - Zhao, Y.
AU - Gasser, T.
AU - Maraganore, D.
AU - Krüger, R.
JO - JOURNAL OF MEDICAL GENETICS
PY - 2012
VL - 49
TODO - 11
SP - 721-726
PB - 
SN - 0022-2593
TODO - 10.1136/jmedgenet-2012-101155
TODO - protein serine threonine kinase;  unclassified drug;  vacuolar protein sorting 35, adult;  aged;  article;  controlled study;  female;  gene;  gene frequency;  genetic analysis;  genetic risk;  genetic variability;  genotype;  human;  major clinical study;  male;  multicenter study;  Parkinson disease;  pathogenicity;  penetrance;  priority journal;  single nucleotide polymorphism, Female;  Genetic Association Studies;  Genetic Predisposition to Disease;  Humans;  Male;  Mutation;  Parkinson Disease;  Risk Factors;  Vesicular Transport Proteins
TODO - 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 multicenter 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 -