A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants

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, 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 and GEOPD consortium (2012) A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants. Journal of Medical Genetics, 49 11: 721-726. doi:10.1136/jmedgenet-2012-101155

Author 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
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
GEOPD consortium
Total Author Count Override 63
Title A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants
Journal name Journal of Medical Genetics   Check publisher's open access policy
ISSN 0022-2593
Publication date 2012-11
Sub-type Article (original research)
DOI 10.1136/jmedgenet-2012-101155
Volume 49
Issue 11
Start page 721
End page 726
Total pages 6
Place of publication London, United Kingdom
Publisher BMJ
Collection year 2013
Language eng
Formatted 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 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.

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.
Keyword Parkinson
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
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Citation counts: TR Web of Science Citation Count  Cited 27 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 28 times in Scopus Article | Citations
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