A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants
View/ Open
Author(s)
Sharma, Manu
Ioannidis, John PA
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
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, 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
Krueger, Rejko
Griffith University Author(s)
Year published
2012
Metadata
Show full item recordAbstract
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 ...
View more >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
View less >
View more >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
View less >
Journal Title
Journal of Medical Genetics
Volume
49
Copyright Statement
© The Author(s) 2012. The attached file is reproduced here in accordance with the copyright policy of the publisher. For information about this journal please refer to the journal’s website or contact the authors.
Subject
Biological sciences
Biomedical and clinical sciences
Neurology and neuromuscular diseases