A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants
Identifieur interne : 001339 ( Main/Corpus ); précédent : 001338; suivant : 001340A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants
Auteurs : Manu Sharma ; John P A. Ioannidis ; Jan O. Aasly ; Grazia Annesi ; Alexis Brice ; Lars Bertram ; Maria Bozi ; Maria Barcikowska ; David Crosiers ; Carl E. Clarke ; Maurizio F. Facheris ; Matthew Farrer ; Gaetan Garraux ; Suzana Gispert ; Georg Auburger ; Carles Vilari O-Güell ; Georgios M. Hadjigeorgiou ; Andrew A. Hicks ; Nobutaka Hattori ; Beom S. Jeon ; Zygmunt Jamrozik ; Anna Krygowska-Wajs ; Suzanne Lesage ; Christina M. Lill ; Juei-Jueng Lin ; Timothy Lynch ; Peter Lichtner ; Anthony E. Lang ; Cecile Libioulle ; Miho Murata ; Vincent Mok ; Barbara Jasinska-Myga ; George D. Mellick ; Karen E. Morrison ; Thomas Meitnger ; Alexander Zimprich ; Grzegorz Opala ; Peter P. Pramstaller ; Irene Pichler ; Sung Sup Park ; Aldo Quattrone ; Ekaterina Rogaeva ; Owen A. Ross ; Leonidas Stefanis ; Joanne D. Stockton ; Wataru Satake ; Peter A. Silburn ; Tim M. Strom ; Jessie Theuns ; Eng- King Tan ; Tatsushi Toda ; Hiroyuki Tomiyama ; Ryan J. Uitti ; Christine Van Broeckhoven ; Karin Wirdefeldt ; Zbigniew Wszolek ; Georgia Xiromerisiou ; Harumi S. Yomono ; Kuo-Chu Yueh ; Yi Zhao ; Thomas Gasser ; Demetrius Maraganore ; Rejko KrügerSource :
- Journal of Medical Genetics [ 0022-2593 ] ; 2012-11.
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.
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DOI: 10.1136/jmedgenet-2012-101155
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants</title><author><name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</name><affiliation><mods:affiliation>Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen</mods:affiliation></affiliation></author><author><name sortKey="Ioannidis, John P A" sort="Ioannidis, John P A" uniqKey="Ioannidis J" first="John P A" last="Ioannidis">John P A. Ioannidis</name><affiliation><mods:affiliation>Stanford Prevention Research Center, Department of Medicine and Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA</mods:affiliation></affiliation></author><author><name sortKey="Aasly, Jan O" sort="Aasly, Jan O" uniqKey="Aasly J" first="Jan O" last="Aasly">Jan O. Aasly</name><affiliation><mods:affiliation>Department of Neurology, St Olavs Hospital and NTNU Trondheim, Trondheim, Norway</mods:affiliation></affiliation></author><author><name sortKey="Annesi, Grazia" sort="Annesi, Grazia" uniqKey="Annesi G" first="Grazia" last="Annesi">Grazia Annesi</name><affiliation><mods:affiliation>Institute of Neurology, Department of Medical Sciences , University Magna Graecia, Catanzaro; Neuroimaging Research Unit, National Research Council, Catanzaro, Italy</mods:affiliation></affiliation></author><author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name><affiliation><mods:affiliation>INSERM, UMR_S975, Université Pierre et Marie Curie-Paris, CNRS, UMR 7225, AP-HP, Pitié-Salpêtriére Hospital</mods:affiliation></affiliation><affiliation><mods:affiliation>Cnrs, UMR 7225, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>AP-HP, Hôpital Pitié-Salpêtiére, Department of Genetics and Cytogenetics, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Bertram, Lars" sort="Bertram, Lars" uniqKey="Bertram L" first="Lars" last="Bertram">Lars Bertram</name><affiliation><mods:affiliation>Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.</mods:affiliation></affiliation></author><author><name sortKey="Bozi, Maria" sort="Bozi, Maria" uniqKey="Bozi M" first="Maria" last="Bozi">Maria Bozi</name><affiliation><mods:affiliation>General Hospital of Syros, Syros, Greece</mods:affiliation></affiliation><affiliation><mods:affiliation>2nd Neurology Clinic, University of Athens, ‘Attikon’ Hospital, Athens, Greece</mods:affiliation></affiliation></author><author><name sortKey="Barcikowska, Maria" sort="Barcikowska, Maria" uniqKey="Barcikowska M" first="Maria" last="Barcikowska">Maria Barcikowska</name><affiliation><mods:affiliation>Department of Neurodegenerative Disorders, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland</mods:affiliation></affiliation></author><author><name sortKey="Crosiers, David" sort="Crosiers, David" uniqKey="Crosiers D" first="David" last="Crosiers">David Crosiers</name><affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.</mods:affiliation></affiliation></author><author><name sortKey="Clarke, Carl E" sort="Clarke, Carl E" uniqKey="Clarke C" first="Carl E" last="Clarke">Carl E. Clarke</name><affiliation><mods:affiliation>School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, City Hospital, Birmingham, UK</mods:affiliation></affiliation></author><author><name sortKey="Facheris, Maurizio F" sort="Facheris, Maurizio F" uniqKey="Facheris M" first="Maurizio F" last="Facheris">Maurizio F. Facheris</name><affiliation><mods:affiliation>Centre for Biomedicine, European Academy Bozen/Bolzano, Itlay, Affiliated institute of the University of Lübeck, Lübeck, German</mods:affiliation></affiliation></author><author><name sortKey="Farrer, Matthew" sort="Farrer, Matthew" uniqKey="Farrer M" first="Matthew" last="Farrer">Matthew Farrer</name><affiliation><mods:affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</mods:affiliation></affiliation></author><author><name sortKey="Garraux, Gaetan" sort="Garraux, Gaetan" uniqKey="Garraux G" first="Gaetan" last="Garraux">Gaetan Garraux</name><affiliation><mods:affiliation>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</mods:affiliation></affiliation></author><author><name sortKey="Gispert, Suzana" sort="Gispert, Suzana" uniqKey="Gispert S" first="Suzana" last="Gispert">Suzana Gispert</name><affiliation><mods:affiliation>Department of Neurology, Goethe University Frankfurt am Main, Frankfurt, Germany</mods:affiliation></affiliation></author><author><name sortKey="Auburger, Georg" sort="Auburger, Georg" uniqKey="Auburger G" first="Georg" last="Auburger">Georg Auburger</name><affiliation><mods:affiliation>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</mods:affiliation></affiliation></author><author><name sortKey="Vilari O Guell, Carles" sort="Vilari O Guell, Carles" uniqKey="Vilari O Guell C" first="Carles" last="Vilari O-Güell">Carles Vilari O-Güell</name><affiliation><mods:affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</mods:affiliation></affiliation></author><author><name sortKey="Hadjigeorgiou, Georgios M" sort="Hadjigeorgiou, Georgios M" uniqKey="Hadjigeorgiou G" first="Georgios M" last="Hadjigeorgiou">Georgios M. Hadjigeorgiou</name><affiliation><mods:affiliation>Department of Neurology, University of Thessaly and Institute of Biomedical Research and Technology, CERETETH, Larissa, Greece</mods:affiliation></affiliation></author><author><name sortKey="Hicks, Andrew A" sort="Hicks, Andrew A" uniqKey="Hicks A" first="Andrew A" last="Hicks">Andrew A. Hicks</name><affiliation><mods:affiliation>Centre for Biomedicine, European Academy Bozen/Bolzano, Itlay, Affiliated institute of the University of Lübeck, Lübeck, German</mods:affiliation></affiliation></author><author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Jeon, Beom S" sort="Jeon, Beom S" uniqKey="Jeon B" first="Beom S" last="Jeon">Beom S. Jeon</name><affiliation><mods:affiliation>Department of Neurology, Seoul National University Hospital, Seoul, Korea</mods:affiliation></affiliation></author><author><name sortKey="Jamrozik, Zygmunt" sort="Jamrozik, Zygmunt" uniqKey="Jamrozik Z" first="Zygmunt" last="Jamrozik">Zygmunt Jamrozik</name><affiliation><mods:affiliation>Department of Neurology, Medical University of Warsaw, Warsaw, Poland</mods:affiliation></affiliation></author><author><name sortKey="Krygowska Wajs, Anna" sort="Krygowska Wajs, Anna" uniqKey="Krygowska Wajs A" first="Anna" last="Krygowska-Wajs">Anna Krygowska-Wajs</name><affiliation><mods:affiliation>Department of Neurology, Jagiellonian University, Krakow, Poland</mods:affiliation></affiliation></author><author><name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name><affiliation><mods:affiliation>INSERM, UMR_S975, Université Pierre et Marie Curie-Paris, CNRS, UMR 7225, AP-HP, Pitié-Salpêtriére Hospital</mods:affiliation></affiliation><affiliation><mods:affiliation>Cnrs, UMR 7225, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>AP-HP, Hôpital Pitié-Salpêtiére, Department of Genetics and Cytogenetics, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Lill, Christina M" sort="Lill, Christina M" uniqKey="Lill C" first="Christina M" last="Lill">Christina M. Lill</name><affiliation><mods:affiliation>General Hospital of Syros, Syros, Greece</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Johannes Gutenberg University, Mainz, Germany</mods:affiliation></affiliation></author><author><name sortKey="Lin, Juei Jueng" sort="Lin, Juei Jueng" uniqKey="Lin J" first="Juei-Jueng" last="Lin">Juei-Jueng Lin</name><affiliation><mods:affiliation>Department of Neurology, Chushang Show-Chwan Hospital, Nantou and Chung-Shan Medical University Hospital, Taichung, Taiwan</mods:affiliation></affiliation></author><author><name sortKey="Lynch, Timothy" sort="Lynch, Timothy" uniqKey="Lynch T" first="Timothy" last="Lynch">Timothy Lynch</name><affiliation><mods:affiliation>The Dublin Neurological Institute at the Mater Misericordiae University Hospital, and Conway Institute, University College Dublin, Dublin, Ireland</mods:affiliation></affiliation></author><author><name sortKey="Lichtner, Peter" sort="Lichtner, Peter" uniqKey="Lichtner P" first="Peter" last="Lichtner">Peter Lichtner</name><affiliation><mods:affiliation>Helmholtz Zentrum München, German Research Centre for Environmental Health (Gmbh), Neuherberg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E" last="Lang">Anthony E. Lang</name><affiliation><mods:affiliation>Movement Disorders Centre, and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Canada</mods:affiliation></affiliation></author><author><name sortKey="Libioulle, Cecile" sort="Libioulle, Cecile" uniqKey="Libioulle C" first="Cecile" last="Libioulle">Cecile Libioulle</name><affiliation><mods:affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</mods:affiliation></affiliation></author><author><name sortKey="Murata, Miho" sort="Murata, Miho" uniqKey="Murata M" first="Miho" last="Murata">Miho Murata</name><affiliation><mods:affiliation>Department of Neurology, National Center Hospital of Neurology and Psychiatry, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Mok, Vincent" sort="Mok, Vincent" uniqKey="Mok V" first="Vincent" last="Mok">Vincent Mok</name><affiliation><mods:affiliation>Department of Medicine and Therapeutics, Prince of Wales Hospital,The Chinese University of Hong Kong, Shatin, Hong Kong</mods:affiliation></affiliation></author><author><name sortKey="Jasinska Myga, Barbara" sort="Jasinska Myga, Barbara" uniqKey="Jasinska Myga B" first="Barbara" last="Jasinska-Myga">Barbara Jasinska-Myga</name><affiliation><mods:affiliation>Department of Neurology, Medical University of Silesia, Katowice, Poland</mods:affiliation></affiliation></author><author><name sortKey="Mellick, George D" sort="Mellick, George D" uniqKey="Mellick G" first="George D" last="Mellick">George D. Mellick</name><affiliation><mods:affiliation>Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Australia</mods:affiliation></affiliation></author><author><name sortKey="Morrison, Karen E" sort="Morrison, Karen E" uniqKey="Morrison K" first="Karen E" last="Morrison">Karen E. Morrison</name><affiliation><mods:affiliation>Centre for Biomedicine, European Academy Bozen/Bolzano, Itlay, Affiliated institute of the University of Lübeck, Lübeck, German</mods:affiliation></affiliation><affiliation><mods:affiliation>Neurosciences Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK</mods:affiliation></affiliation></author><author><name sortKey="Meitnger, Thomas" sort="Meitnger, Thomas" uniqKey="Meitnger T" first="Thomas" last="Meitnger">Thomas Meitnger</name><affiliation><mods:affiliation>German Research Center for Environmental Health, Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Institute of Human Genetics, Technische Universität München, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Zimprich, Alexander" sort="Zimprich, Alexander" uniqKey="Zimprich A" first="Alexander" last="Zimprich">Alexander Zimprich</name><affiliation><mods:affiliation>Department of Neurology, Medizinische Universität Wien, Vienna, Austria</mods:affiliation></affiliation></author><author><name sortKey="Opala, Grzegorz" sort="Opala, Grzegorz" uniqKey="Opala G" first="Grzegorz" last="Opala">Grzegorz Opala</name><affiliation><mods:affiliation>German Research Center for Environmental Health, Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Pramstaller, Peter P" sort="Pramstaller, Peter P" uniqKey="Pramstaller P" first="Peter P" last="Pramstaller">Peter P. Pramstaller</name><affiliation><mods:affiliation>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</mods:affiliation></affiliation></author><author><name sortKey="Pichler, Irene" sort="Pichler, Irene" uniqKey="Pichler I" first="Irene" last="Pichler">Irene Pichler</name><affiliation><mods:affiliation>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</mods:affiliation></affiliation></author><author><name sortKey="Park, Sung Sup" sort="Park, Sung Sup" uniqKey="Park S" first="Sung Sup" last="Park">Sung Sup Park</name><affiliation><mods:affiliation>Department of Neurology, Johannes Gutenberg University, Mainz, Germany</mods:affiliation></affiliation></author><author><name sortKey="Quattrone, Aldo" sort="Quattrone, Aldo" uniqKey="Quattrone A" first="Aldo" last="Quattrone">Aldo Quattrone</name><affiliation><mods:affiliation>Institute of Neurology, Department of Medical Sciences , University Magna Graecia, Catanzaro; Neuroimaging Research Unit, National Research Council, Catanzaro, Italy</mods:affiliation></affiliation></author><author><name sortKey="Rogaeva, Ekaterina" sort="Rogaeva, Ekaterina" uniqKey="Rogaeva E" first="Ekaterina" last="Rogaeva">Ekaterina Rogaeva</name><affiliation><mods:affiliation>Tanz Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Toronto, Canada</mods:affiliation></affiliation></author><author><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A." last="Ross">Owen A. Ross</name><affiliation><mods:affiliation>Department of Neuroscience, Mayo Clinic, Jacksonville, Florida</mods:affiliation></affiliation></author><author><name sortKey="Stefanis, Leonidas" sort="Stefanis, Leonidas" uniqKey="Stefanis L" first="Leonidas" last="Stefanis">Leonidas Stefanis</name><affiliation><mods:affiliation>2nd Neurology Clinic, University of Athens, ‘Attikon’ Hospital, Athens, Greece</mods:affiliation></affiliation><affiliation><mods:affiliation>Divisions of Basic Neurosciences & Cell Biology, Biomedical Research Foundation of Academy of Athens, Athens, Greece</mods:affiliation></affiliation></author><author><name sortKey="Stockton, Joanne D" sort="Stockton, Joanne D" uniqKey="Stockton J" first="Joanne D" last="Stockton">Joanne D. Stockton</name><affiliation><mods:affiliation>Neurosciences Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK</mods:affiliation></affiliation></author><author><name sortKey="Satake, Wataru" sort="Satake, Wataru" uniqKey="Satake W" first="Wataru" last="Satake">Wataru Satake</name><affiliation><mods:affiliation>Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan</mods:affiliation></affiliation></author><author><name sortKey="Silburn, Peter A" sort="Silburn, Peter A" uniqKey="Silburn P" first="Peter A" last="Silburn">Peter A. Silburn</name><affiliation><mods:affiliation>University of Queensland Centre for Clinical Research, Herston, Australia</mods:affiliation></affiliation></author><author><name sortKey="Strom, Tim M" sort="Strom, Tim M" uniqKey="Strom T" first="Tim M" last="Strom">Tim M. Strom</name><affiliation><mods:affiliation>Institute of Human Genetics, Technische Universität München, Munich, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Tanz Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Toronto, Canada</mods:affiliation></affiliation></author><author><name sortKey="Theuns, Jessie" sort="Theuns, Jessie" uniqKey="Theuns J" first="Jessie" last="Theuns">Jessie Theuns</name><affiliation><mods:affiliation>Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.</mods:affiliation></affiliation></author><author><name sortKey="Tan, Eng King" sort="Tan, Eng King" uniqKey="Tan E" first="Eng- King" last="Tan">Eng- King Tan</name><affiliation><mods:affiliation>Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Toda, Tatsushi" sort="Toda, Tatsushi" uniqKey="Toda T" first="Tatsushi" last="Toda">Tatsushi Toda</name><affiliation><mods:affiliation>Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan</mods:affiliation></affiliation></author><author><name sortKey="Tomiyama, Hiroyuki" sort="Tomiyama, Hiroyuki" uniqKey="Tomiyama H" first="Hiroyuki" last="Tomiyama">Hiroyuki Tomiyama</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Uitti, Ryan J" sort="Uitti, Ryan J" uniqKey="Uitti R" first="Ryan J" last="Uitti">Ryan J. Uitti</name><affiliation><mods:affiliation>Department of Neurology, Mayo Clinic Jacksonville, USA</mods:affiliation></affiliation></author><author><name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name><affiliation><mods:affiliation>Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.</mods:affiliation></affiliation></author><author><name sortKey="Wirdefeldt, Karin" sort="Wirdefeldt, Karin" uniqKey="Wirdefeldt K" first="Karin" last="Wirdefeldt">Karin Wirdefeldt</name><affiliation><mods:affiliation>Epidemiology and Biostatistics and Department of Clinical Neuroscience, Karolinska Institutet</mods:affiliation></affiliation></author><author><name sortKey="Wszolek, Zbigniew" sort="Wszolek, Zbigniew" uniqKey="Wszolek Z" first="Zbigniew" last="Wszolek">Zbigniew Wszolek</name><affiliation><mods:affiliation>Department of Neurology, Mayo Clinic Jacksonville, USA</mods:affiliation></affiliation></author><author><name sortKey="Xiromerisiou, Georgia" sort="Xiromerisiou, Georgia" uniqKey="Xiromerisiou G" first="Georgia" last="Xiromerisiou">Georgia Xiromerisiou</name><affiliation><mods:affiliation>Department of Neurology, University of Thessaly and Institute of Biomedical Research and Technology, CERETETH, Larissa, Greece</mods:affiliation></affiliation></author><author><name sortKey="Yomono, Harumi S" sort="Yomono, Harumi S" uniqKey="Yomono H" first="Harumi S" last="Yomono">Harumi S. Yomono</name><affiliation><mods:affiliation>Department of Neurology, National Hospital Organization Tokyo Hospital, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Yueh, Kuo Chu" sort="Yueh, Kuo Chu" uniqKey="Yueh K" first="Kuo-Chu" last="Yueh">Kuo-Chu Yueh</name><affiliation><mods:affiliation>Department of Neurology, Chushang Show-Chwan Hospital, Nantou and Chung-Shan Medical University Hospital, Taichung, Taiwan</mods:affiliation></affiliation></author><author><name sortKey="Zhao, Yi" sort="Zhao, Yi" uniqKey="Zhao Y" first="Yi" last="Zhao">Yi Zhao</name></author><author><name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name><affiliation><mods:affiliation>Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen</mods:affiliation></affiliation></author><author><name sortKey="Maraganore, Demetrius" sort="Maraganore, Demetrius" uniqKey="Maraganore D" first="Demetrius" last="Maraganore">Demetrius Maraganore</name><affiliation><mods:affiliation>Department of Neurology, NorthShore University HealthSystem, Chicago, USA</mods:affiliation></affiliation></author><author><name sortKey="Kruger, Rejko" sort="Kruger, Rejko" uniqKey="Kruger R" first="Rejko" last="Krüger">Rejko Krüger</name><affiliation><mods:affiliation>Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:1E80C3110D21541A237742CD339DD00EB1BB056D</idno><date when="2012" year="2012">2012</date><idno type="doi">10.1136/jmedgenet-2012-101155</idno><idno type="url">https://api.istex.fr/document/1E80C3110D21541A237742CD339DD00EB1BB056D/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001339</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants</title><author><name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</name><affiliation><mods:affiliation>Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen</mods:affiliation></affiliation></author><author><name sortKey="Ioannidis, John P A" sort="Ioannidis, John P A" uniqKey="Ioannidis J" first="John P A" last="Ioannidis">John P A. Ioannidis</name><affiliation><mods:affiliation>Stanford Prevention Research Center, Department of Medicine and Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA</mods:affiliation></affiliation></author><author><name sortKey="Aasly, Jan O" sort="Aasly, Jan O" uniqKey="Aasly J" first="Jan O" last="Aasly">Jan O. Aasly</name><affiliation><mods:affiliation>Department of Neurology, St Olavs Hospital and NTNU Trondheim, Trondheim, Norway</mods:affiliation></affiliation></author><author><name sortKey="Annesi, Grazia" sort="Annesi, Grazia" uniqKey="Annesi G" first="Grazia" last="Annesi">Grazia Annesi</name><affiliation><mods:affiliation>Institute of Neurology, Department of Medical Sciences , University Magna Graecia, Catanzaro; Neuroimaging Research Unit, National Research Council, Catanzaro, Italy</mods:affiliation></affiliation></author><author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name><affiliation><mods:affiliation>INSERM, UMR_S975, Université Pierre et Marie Curie-Paris, CNRS, UMR 7225, AP-HP, Pitié-Salpêtriére Hospital</mods:affiliation></affiliation><affiliation><mods:affiliation>Cnrs, UMR 7225, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>AP-HP, Hôpital Pitié-Salpêtiére, Department of Genetics and Cytogenetics, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Bertram, Lars" sort="Bertram, Lars" uniqKey="Bertram L" first="Lars" last="Bertram">Lars Bertram</name><affiliation><mods:affiliation>Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.</mods:affiliation></affiliation></author><author><name sortKey="Bozi, Maria" sort="Bozi, Maria" uniqKey="Bozi M" first="Maria" last="Bozi">Maria Bozi</name><affiliation><mods:affiliation>General Hospital of Syros, Syros, Greece</mods:affiliation></affiliation><affiliation><mods:affiliation>2nd Neurology Clinic, University of Athens, ‘Attikon’ Hospital, Athens, Greece</mods:affiliation></affiliation></author><author><name sortKey="Barcikowska, Maria" sort="Barcikowska, Maria" uniqKey="Barcikowska M" first="Maria" last="Barcikowska">Maria Barcikowska</name><affiliation><mods:affiliation>Department of Neurodegenerative Disorders, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland</mods:affiliation></affiliation></author><author><name sortKey="Crosiers, David" sort="Crosiers, David" uniqKey="Crosiers D" first="David" last="Crosiers">David Crosiers</name><affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.</mods:affiliation></affiliation></author><author><name sortKey="Clarke, Carl E" sort="Clarke, Carl E" uniqKey="Clarke C" first="Carl E" last="Clarke">Carl E. Clarke</name><affiliation><mods:affiliation>School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, City Hospital, Birmingham, UK</mods:affiliation></affiliation></author><author><name sortKey="Facheris, Maurizio F" sort="Facheris, Maurizio F" uniqKey="Facheris M" first="Maurizio F" last="Facheris">Maurizio F. Facheris</name><affiliation><mods:affiliation>Centre for Biomedicine, European Academy Bozen/Bolzano, Itlay, Affiliated institute of the University of Lübeck, Lübeck, German</mods:affiliation></affiliation></author><author><name sortKey="Farrer, Matthew" sort="Farrer, Matthew" uniqKey="Farrer M" first="Matthew" last="Farrer">Matthew Farrer</name><affiliation><mods:affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</mods:affiliation></affiliation></author><author><name sortKey="Garraux, Gaetan" sort="Garraux, Gaetan" uniqKey="Garraux G" first="Gaetan" last="Garraux">Gaetan Garraux</name><affiliation><mods:affiliation>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</mods:affiliation></affiliation></author><author><name sortKey="Gispert, Suzana" sort="Gispert, Suzana" uniqKey="Gispert S" first="Suzana" last="Gispert">Suzana Gispert</name><affiliation><mods:affiliation>Department of Neurology, Goethe University Frankfurt am Main, Frankfurt, Germany</mods:affiliation></affiliation></author><author><name sortKey="Auburger, Georg" sort="Auburger, Georg" uniqKey="Auburger G" first="Georg" last="Auburger">Georg Auburger</name><affiliation><mods:affiliation>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</mods:affiliation></affiliation></author><author><name sortKey="Vilari O Guell, Carles" sort="Vilari O Guell, Carles" uniqKey="Vilari O Guell C" first="Carles" last="Vilari O-Güell">Carles Vilari O-Güell</name><affiliation><mods:affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</mods:affiliation></affiliation></author><author><name sortKey="Hadjigeorgiou, Georgios M" sort="Hadjigeorgiou, Georgios M" uniqKey="Hadjigeorgiou G" first="Georgios M" last="Hadjigeorgiou">Georgios M. Hadjigeorgiou</name><affiliation><mods:affiliation>Department of Neurology, University of Thessaly and Institute of Biomedical Research and Technology, CERETETH, Larissa, Greece</mods:affiliation></affiliation></author><author><name sortKey="Hicks, Andrew A" sort="Hicks, Andrew A" uniqKey="Hicks A" first="Andrew A" last="Hicks">Andrew A. Hicks</name><affiliation><mods:affiliation>Centre for Biomedicine, European Academy Bozen/Bolzano, Itlay, Affiliated institute of the University of Lübeck, Lübeck, German</mods:affiliation></affiliation></author><author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Jeon, Beom S" sort="Jeon, Beom S" uniqKey="Jeon B" first="Beom S" last="Jeon">Beom S. Jeon</name><affiliation><mods:affiliation>Department of Neurology, Seoul National University Hospital, Seoul, Korea</mods:affiliation></affiliation></author><author><name sortKey="Jamrozik, Zygmunt" sort="Jamrozik, Zygmunt" uniqKey="Jamrozik Z" first="Zygmunt" last="Jamrozik">Zygmunt Jamrozik</name><affiliation><mods:affiliation>Department of Neurology, Medical University of Warsaw, Warsaw, Poland</mods:affiliation></affiliation></author><author><name sortKey="Krygowska Wajs, Anna" sort="Krygowska Wajs, Anna" uniqKey="Krygowska Wajs A" first="Anna" last="Krygowska-Wajs">Anna Krygowska-Wajs</name><affiliation><mods:affiliation>Department of Neurology, Jagiellonian University, Krakow, Poland</mods:affiliation></affiliation></author><author><name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name><affiliation><mods:affiliation>INSERM, UMR_S975, Université Pierre et Marie Curie-Paris, CNRS, UMR 7225, AP-HP, Pitié-Salpêtriére Hospital</mods:affiliation></affiliation><affiliation><mods:affiliation>Cnrs, UMR 7225, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>AP-HP, Hôpital Pitié-Salpêtiére, Department of Genetics and Cytogenetics, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Lill, Christina M" sort="Lill, Christina M" uniqKey="Lill C" first="Christina M" last="Lill">Christina M. Lill</name><affiliation><mods:affiliation>General Hospital of Syros, Syros, Greece</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Johannes Gutenberg University, Mainz, Germany</mods:affiliation></affiliation></author><author><name sortKey="Lin, Juei Jueng" sort="Lin, Juei Jueng" uniqKey="Lin J" first="Juei-Jueng" last="Lin">Juei-Jueng Lin</name><affiliation><mods:affiliation>Department of Neurology, Chushang Show-Chwan Hospital, Nantou and Chung-Shan Medical University Hospital, Taichung, Taiwan</mods:affiliation></affiliation></author><author><name sortKey="Lynch, Timothy" sort="Lynch, Timothy" uniqKey="Lynch T" first="Timothy" last="Lynch">Timothy Lynch</name><affiliation><mods:affiliation>The Dublin Neurological Institute at the Mater Misericordiae University Hospital, and Conway Institute, University College Dublin, Dublin, Ireland</mods:affiliation></affiliation></author><author><name sortKey="Lichtner, Peter" sort="Lichtner, Peter" uniqKey="Lichtner P" first="Peter" last="Lichtner">Peter Lichtner</name><affiliation><mods:affiliation>Helmholtz Zentrum München, German Research Centre for Environmental Health (Gmbh), Neuherberg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E" last="Lang">Anthony E. Lang</name><affiliation><mods:affiliation>Movement Disorders Centre, and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Canada</mods:affiliation></affiliation></author><author><name sortKey="Libioulle, Cecile" sort="Libioulle, Cecile" uniqKey="Libioulle C" first="Cecile" last="Libioulle">Cecile Libioulle</name><affiliation><mods:affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</mods:affiliation></affiliation></author><author><name sortKey="Murata, Miho" sort="Murata, Miho" uniqKey="Murata M" first="Miho" last="Murata">Miho Murata</name><affiliation><mods:affiliation>Department of Neurology, National Center Hospital of Neurology and Psychiatry, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Mok, Vincent" sort="Mok, Vincent" uniqKey="Mok V" first="Vincent" last="Mok">Vincent Mok</name><affiliation><mods:affiliation>Department of Medicine and Therapeutics, Prince of Wales Hospital,The Chinese University of Hong Kong, Shatin, Hong Kong</mods:affiliation></affiliation></author><author><name sortKey="Jasinska Myga, Barbara" sort="Jasinska Myga, Barbara" uniqKey="Jasinska Myga B" first="Barbara" last="Jasinska-Myga">Barbara Jasinska-Myga</name><affiliation><mods:affiliation>Department of Neurology, Medical University of Silesia, Katowice, Poland</mods:affiliation></affiliation></author><author><name sortKey="Mellick, George D" sort="Mellick, George D" uniqKey="Mellick G" first="George D" last="Mellick">George D. Mellick</name><affiliation><mods:affiliation>Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Australia</mods:affiliation></affiliation></author><author><name sortKey="Morrison, Karen E" sort="Morrison, Karen E" uniqKey="Morrison K" first="Karen E" last="Morrison">Karen E. Morrison</name><affiliation><mods:affiliation>Centre for Biomedicine, European Academy Bozen/Bolzano, Itlay, Affiliated institute of the University of Lübeck, Lübeck, German</mods:affiliation></affiliation><affiliation><mods:affiliation>Neurosciences Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK</mods:affiliation></affiliation></author><author><name sortKey="Meitnger, Thomas" sort="Meitnger, Thomas" uniqKey="Meitnger T" first="Thomas" last="Meitnger">Thomas Meitnger</name><affiliation><mods:affiliation>German Research Center for Environmental Health, Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Institute of Human Genetics, Technische Universität München, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Zimprich, Alexander" sort="Zimprich, Alexander" uniqKey="Zimprich A" first="Alexander" last="Zimprich">Alexander Zimprich</name><affiliation><mods:affiliation>Department of Neurology, Medizinische Universität Wien, Vienna, Austria</mods:affiliation></affiliation></author><author><name sortKey="Opala, Grzegorz" sort="Opala, Grzegorz" uniqKey="Opala G" first="Grzegorz" last="Opala">Grzegorz Opala</name><affiliation><mods:affiliation>German Research Center for Environmental Health, Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Pramstaller, Peter P" sort="Pramstaller, Peter P" uniqKey="Pramstaller P" first="Peter P" last="Pramstaller">Peter P. Pramstaller</name><affiliation><mods:affiliation>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</mods:affiliation></affiliation></author><author><name sortKey="Pichler, Irene" sort="Pichler, Irene" uniqKey="Pichler I" first="Irene" last="Pichler">Irene Pichler</name><affiliation><mods:affiliation>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</mods:affiliation></affiliation></author><author><name sortKey="Park, Sung Sup" sort="Park, Sung Sup" uniqKey="Park S" first="Sung Sup" last="Park">Sung Sup Park</name><affiliation><mods:affiliation>Department of Neurology, Johannes Gutenberg University, Mainz, Germany</mods:affiliation></affiliation></author><author><name sortKey="Quattrone, Aldo" sort="Quattrone, Aldo" uniqKey="Quattrone A" first="Aldo" last="Quattrone">Aldo Quattrone</name><affiliation><mods:affiliation>Institute of Neurology, Department of Medical Sciences , University Magna Graecia, Catanzaro; Neuroimaging Research Unit, National Research Council, Catanzaro, Italy</mods:affiliation></affiliation></author><author><name sortKey="Rogaeva, Ekaterina" sort="Rogaeva, Ekaterina" uniqKey="Rogaeva E" first="Ekaterina" last="Rogaeva">Ekaterina Rogaeva</name><affiliation><mods:affiliation>Tanz Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Toronto, Canada</mods:affiliation></affiliation></author><author><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A." last="Ross">Owen A. Ross</name><affiliation><mods:affiliation>Department of Neuroscience, Mayo Clinic, Jacksonville, Florida</mods:affiliation></affiliation></author><author><name sortKey="Stefanis, Leonidas" sort="Stefanis, Leonidas" uniqKey="Stefanis L" first="Leonidas" last="Stefanis">Leonidas Stefanis</name><affiliation><mods:affiliation>2nd Neurology Clinic, University of Athens, ‘Attikon’ Hospital, Athens, Greece</mods:affiliation></affiliation><affiliation><mods:affiliation>Divisions of Basic Neurosciences & Cell Biology, Biomedical Research Foundation of Academy of Athens, Athens, Greece</mods:affiliation></affiliation></author><author><name sortKey="Stockton, Joanne D" sort="Stockton, Joanne D" uniqKey="Stockton J" first="Joanne D" last="Stockton">Joanne D. Stockton</name><affiliation><mods:affiliation>Neurosciences Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK</mods:affiliation></affiliation></author><author><name sortKey="Satake, Wataru" sort="Satake, Wataru" uniqKey="Satake W" first="Wataru" last="Satake">Wataru Satake</name><affiliation><mods:affiliation>Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan</mods:affiliation></affiliation></author><author><name sortKey="Silburn, Peter A" sort="Silburn, Peter A" uniqKey="Silburn P" first="Peter A" last="Silburn">Peter A. Silburn</name><affiliation><mods:affiliation>University of Queensland Centre for Clinical Research, Herston, Australia</mods:affiliation></affiliation></author><author><name sortKey="Strom, Tim M" sort="Strom, Tim M" uniqKey="Strom T" first="Tim M" last="Strom">Tim M. Strom</name><affiliation><mods:affiliation>Institute of Human Genetics, Technische Universität München, Munich, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Tanz Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Toronto, Canada</mods:affiliation></affiliation></author><author><name sortKey="Theuns, Jessie" sort="Theuns, Jessie" uniqKey="Theuns J" first="Jessie" last="Theuns">Jessie Theuns</name><affiliation><mods:affiliation>Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.</mods:affiliation></affiliation></author><author><name sortKey="Tan, Eng King" sort="Tan, Eng King" uniqKey="Tan E" first="Eng- King" last="Tan">Eng- King Tan</name><affiliation><mods:affiliation>Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Toda, Tatsushi" sort="Toda, Tatsushi" uniqKey="Toda T" first="Tatsushi" last="Toda">Tatsushi Toda</name><affiliation><mods:affiliation>Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan</mods:affiliation></affiliation></author><author><name sortKey="Tomiyama, Hiroyuki" sort="Tomiyama, Hiroyuki" uniqKey="Tomiyama H" first="Hiroyuki" last="Tomiyama">Hiroyuki Tomiyama</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Uitti, Ryan J" sort="Uitti, Ryan J" uniqKey="Uitti R" first="Ryan J" last="Uitti">Ryan J. Uitti</name><affiliation><mods:affiliation>Department of Neurology, Mayo Clinic Jacksonville, USA</mods:affiliation></affiliation></author><author><name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name><affiliation><mods:affiliation>Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.</mods:affiliation></affiliation></author><author><name sortKey="Wirdefeldt, Karin" sort="Wirdefeldt, Karin" uniqKey="Wirdefeldt K" first="Karin" last="Wirdefeldt">Karin Wirdefeldt</name><affiliation><mods:affiliation>Epidemiology and Biostatistics and Department of Clinical Neuroscience, Karolinska Institutet</mods:affiliation></affiliation></author><author><name sortKey="Wszolek, Zbigniew" sort="Wszolek, Zbigniew" uniqKey="Wszolek Z" first="Zbigniew" last="Wszolek">Zbigniew Wszolek</name><affiliation><mods:affiliation>Department of Neurology, Mayo Clinic Jacksonville, USA</mods:affiliation></affiliation></author><author><name sortKey="Xiromerisiou, Georgia" sort="Xiromerisiou, Georgia" uniqKey="Xiromerisiou G" first="Georgia" last="Xiromerisiou">Georgia Xiromerisiou</name><affiliation><mods:affiliation>Department of Neurology, University of Thessaly and Institute of Biomedical Research and Technology, CERETETH, Larissa, Greece</mods:affiliation></affiliation></author><author><name sortKey="Yomono, Harumi S" sort="Yomono, Harumi S" uniqKey="Yomono H" first="Harumi S" last="Yomono">Harumi S. Yomono</name><affiliation><mods:affiliation>Department of Neurology, National Hospital Organization Tokyo Hospital, Tokyo, Japan</mods:affiliation></affiliation></author><author><name sortKey="Yueh, Kuo Chu" sort="Yueh, Kuo Chu" uniqKey="Yueh K" first="Kuo-Chu" last="Yueh">Kuo-Chu Yueh</name><affiliation><mods:affiliation>Department of Neurology, Chushang Show-Chwan Hospital, Nantou and Chung-Shan Medical University Hospital, Taichung, Taiwan</mods:affiliation></affiliation></author><author><name sortKey="Zhao, Yi" sort="Zhao, Yi" uniqKey="Zhao Y" first="Yi" last="Zhao">Yi Zhao</name></author><author><name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name><affiliation><mods:affiliation>Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen</mods:affiliation></affiliation></author><author><name sortKey="Maraganore, Demetrius" sort="Maraganore, Demetrius" uniqKey="Maraganore D" first="Demetrius" last="Maraganore">Demetrius Maraganore</name><affiliation><mods:affiliation>Department of Neurology, NorthShore University HealthSystem, Chicago, USA</mods:affiliation></affiliation></author><author><name sortKey="Kruger, Rejko" sort="Kruger, Rejko" uniqKey="Kruger R" first="Rejko" last="Krüger">Rejko Krüger</name><affiliation><mods:affiliation>Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Medical Genetics</title><title level="j" type="abbrev">J Med Genet</title><idno type="ISSN">0022-2593</idno><idno type="eISSN">1468-6244</idno><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2012-11">2012-11</date><biblScope unit="volume">49</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="721">721</biblScope></imprint><idno type="ISSN">0022-2593</idno></series><idno type="istex">1E80C3110D21541A237742CD339DD00EB1BB056D</idno><idno type="DOI">10.1136/jmedgenet-2012-101155</idno><idno type="href">jmedgenet-49-721.pdf</idno><idno type="ArticleID">jmedgenet-2012-101155</idno><idno type="local">jmedgenet;49/11/721</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-2593</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="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.</div></front></TEI><istex><corpusName>bmj</corpusName><author><json:item><name>Manu Sharma</name><affiliations><json:string>Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen</json:string></affiliations></json:item><json:item><name>John P A Ioannidis</name><affiliations><json:string>Stanford Prevention Research Center, Department of Medicine and Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA</json:string></affiliations></json:item><json:item><name>Jan O Aasly</name><affiliations><json:string>Department of Neurology, St Olavs Hospital and NTNU Trondheim, Trondheim, Norway</json:string></affiliations></json:item><json:item><name>Grazia Annesi</name><affiliations><json:string>Institute of Neurology, Department of Medical Sciences , University Magna Graecia, Catanzaro; Neuroimaging Research Unit, National Research Council, Catanzaro, Italy</json:string></affiliations></json:item><json:item><name>Alexis Brice</name><affiliations><json:string>INSERM, UMR_S975, Université Pierre et Marie Curie-Paris, CNRS, UMR 7225, AP-HP, Pitié-Salpêtriére Hospital</json:string><json:string>Cnrs, UMR 7225, Paris, France</json:string><json:string>AP-HP, Hôpital Pitié-Salpêtiére, Department of Genetics and Cytogenetics, Paris, France</json:string></affiliations></json:item><json:item><name>Lars Bertram</name><affiliations><json:string>Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.</json:string></affiliations></json:item><json:item><name>Maria Bozi</name><affiliations><json:string>General Hospital of Syros, Syros, Greece</json:string><json:string>2nd Neurology Clinic, University of Athens, ‘Attikon’ Hospital, Athens, Greece</json:string></affiliations></json:item><json:item><name>Maria Barcikowska</name><affiliations><json:string>Department of Neurodegenerative Disorders, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland</json:string></affiliations></json:item><json:item><name>David Crosiers</name><affiliations><json:string>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium</json:string><json:string>Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</json:string><json:string>Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.</json:string></affiliations></json:item><json:item><name>Carl E Clarke</name><affiliations><json:string>School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, City Hospital, Birmingham, UK</json:string></affiliations></json:item><json:item><name>Maurizio F Facheris</name><affiliations><json:string>Centre for Biomedicine, European Academy Bozen/Bolzano, Itlay, Affiliated institute of the University of Lübeck, Lübeck, German</json:string></affiliations></json:item><json:item><name>Matthew Farrer</name><affiliations><json:string>Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</json:string></affiliations></json:item><json:item><name>Gaetan Garraux</name><affiliations><json:string>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</json:string></affiliations></json:item><json:item><name>Suzana Gispert</name><affiliations><json:string>Department of Neurology, Goethe University Frankfurt am Main, Frankfurt, Germany</json:string></affiliations></json:item><json:item><name>Georg Auburger</name><affiliations><json:string>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</json:string></affiliations></json:item><json:item><name>Carles Vilariño-Güell</name><affiliations><json:string>Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</json:string></affiliations></json:item><json:item><name>Georgios M Hadjigeorgiou</name><affiliations><json:string>Department of Neurology, University of Thessaly and Institute of Biomedical Research and Technology, CERETETH, Larissa, Greece</json:string></affiliations></json:item><json:item><name>Andrew A Hicks</name><affiliations><json:string>Centre for Biomedicine, European Academy Bozen/Bolzano, Itlay, Affiliated institute of the University of Lübeck, Lübeck, German</json:string></affiliations></json:item><json:item><name>Nobutaka Hattori</name><affiliations><json:string>Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan</json:string></affiliations></json:item><json:item><name>Beom S Jeon</name><affiliations><json:string>Department of Neurology, Seoul National University Hospital, Seoul, Korea</json:string></affiliations></json:item><json:item><name>Zygmunt Jamrozik</name><affiliations><json:string>Department of Neurology, Medical University of Warsaw, Warsaw, Poland</json:string></affiliations></json:item><json:item><name>Anna Krygowska-Wajs</name><affiliations><json:string>Department of Neurology, Jagiellonian University, Krakow, Poland</json:string></affiliations></json:item><json:item><name>Suzanne Lesage</name><affiliations><json:string>INSERM, UMR_S975, Université Pierre et Marie Curie-Paris, CNRS, UMR 7225, AP-HP, Pitié-Salpêtriére Hospital</json:string><json:string>Cnrs, UMR 7225, Paris, France</json:string><json:string>AP-HP, Hôpital Pitié-Salpêtiére, Department of Genetics and Cytogenetics, Paris, France</json:string></affiliations></json:item><json:item><name>Christina M Lill</name><affiliations><json:string>General Hospital of Syros, Syros, Greece</json:string><json:string>Department of Neurology, Johannes Gutenberg University, Mainz, Germany</json:string></affiliations></json:item><json:item><name>Juei-Jueng Lin</name><affiliations><json:string>Department of Neurology, Chushang Show-Chwan Hospital, Nantou and Chung-Shan Medical University Hospital, Taichung, Taiwan</json:string></affiliations></json:item><json:item><name>Timothy Lynch</name><affiliations><json:string>The Dublin Neurological Institute at the Mater Misericordiae University Hospital, and Conway Institute, University College Dublin, Dublin, Ireland</json:string></affiliations></json:item><json:item><name>Peter Lichtner</name><affiliations><json:string>Helmholtz Zentrum München, German Research Centre for Environmental Health (Gmbh), Neuherberg, Germany</json:string></affiliations></json:item><json:item><name>Anthony E Lang</name><affiliations><json:string>Movement Disorders Centre, and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Canada</json:string></affiliations></json:item><json:item><name>Cecile Libioulle</name><affiliations><json:string>Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</json:string></affiliations></json:item><json:item><name>Miho Murata</name><affiliations><json:string>Department of Neurology, National Center Hospital of Neurology and Psychiatry, Tokyo, Japan</json:string></affiliations></json:item><json:item><name>Vincent Mok</name><affiliations><json:string>Department of Medicine and Therapeutics, Prince of Wales Hospital,The Chinese University of Hong Kong, Shatin, Hong Kong</json:string></affiliations></json:item><json:item><name>Barbara Jasinska-Myga</name><affiliations><json:string>Department of Neurology, Medical University of Silesia, Katowice, Poland</json:string></affiliations></json:item><json:item><name>George D Mellick</name><affiliations><json:string>Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Australia</json:string></affiliations></json:item><json:item><name>Karen E Morrison</name><affiliations><json:string>Centre for Biomedicine, European Academy Bozen/Bolzano, Itlay, Affiliated institute of the University of Lübeck, Lübeck, German</json:string><json:string>Neurosciences Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK</json:string></affiliations></json:item><json:item><name>Thomas Meitnger</name><affiliations><json:string>German Research Center for Environmental Health, Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany</json:string><json:string>Institute of Human Genetics, Technische Universität München, Munich, Germany</json:string></affiliations></json:item><json:item><name>Alexander Zimprich</name><affiliations><json:string>Department of Neurology, Medizinische Universität Wien, Vienna, Austria</json:string></affiliations></json:item><json:item><name>Grzegorz Opala</name><affiliations><json:string>German Research Center for Environmental Health, Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany</json:string></affiliations></json:item><json:item><name>Peter P Pramstaller</name><affiliations><json:string>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</json:string></affiliations></json:item><json:item><name>Irene Pichler</name><affiliations><json:string>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</json:string></affiliations></json:item><json:item><name>Sung Sup Park</name><affiliations><json:string>Department of Neurology, Johannes Gutenberg University, Mainz, Germany</json:string></affiliations></json:item><json:item><name>Aldo Quattrone</name><affiliations><json:string>Institute of Neurology, Department of Medical Sciences , University Magna Graecia, Catanzaro; Neuroimaging Research Unit, National Research Council, Catanzaro, Italy</json:string></affiliations></json:item><json:item><name>Ekaterina Rogaeva</name><affiliations><json:string>Tanz Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Toronto, Canada</json:string></affiliations></json:item><json:item><name>Owen A. Ross</name><affiliations><json:string>Department of Neuroscience, Mayo Clinic, Jacksonville, Florida</json:string></affiliations></json:item><json:item><name>Leonidas Stefanis</name><affiliations><json:string>2nd Neurology Clinic, University of Athens, ‘Attikon’ Hospital, Athens, Greece</json:string><json:string>Divisions of Basic Neurosciences & Cell Biology, Biomedical Research Foundation of Academy of Athens, Athens, Greece</json:string></affiliations></json:item><json:item><name>Joanne D Stockton</name><affiliations><json:string>Neurosciences Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK</json:string></affiliations></json:item><json:item><name>Wataru Satake</name><affiliations><json:string>Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan</json:string></affiliations></json:item><json:item><name>Peter A Silburn</name><affiliations><json:string>University of Queensland Centre for Clinical Research, Herston, Australia</json:string></affiliations></json:item><json:item><name>Tim M Strom</name><affiliations><json:string>Institute of Human Genetics, Technische Universität München, Munich, Germany</json:string><json:string>Tanz Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Toronto, Canada</json:string></affiliations></json:item><json:item><name>Jessie Theuns</name><affiliations><json:string>Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</json:string><json:string>Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.</json:string></affiliations></json:item><json:item><name>Eng- King Tan</name><affiliations><json:string>Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore</json:string></affiliations></json:item><json:item><name>Tatsushi Toda</name><affiliations><json:string>Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan</json:string></affiliations></json:item><json:item><name>Hiroyuki Tomiyama</name><affiliations><json:string>Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan</json:string></affiliations></json:item><json:item><name>Ryan J Uitti</name><affiliations><json:string>Department of Neurology, Mayo Clinic Jacksonville, USA</json:string></affiliations></json:item><json:item><name>Christine Van Broeckhoven</name><affiliations><json:string>Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</json:string><json:string>Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.</json:string></affiliations></json:item><json:item><name>Karin Wirdefeldt</name><affiliations><json:string>Epidemiology and Biostatistics and Department of Clinical Neuroscience, Karolinska Institutet</json:string></affiliations></json:item><json:item><name>Zbigniew Wszolek</name><affiliations><json:string>Department of Neurology, Mayo Clinic Jacksonville, USA</json:string></affiliations></json:item><json:item><name>Georgia Xiromerisiou</name><affiliations><json:string>Department of Neurology, University of Thessaly and Institute of Biomedical Research and Technology, CERETETH, Larissa, Greece</json:string></affiliations></json:item><json:item><name>Harumi S Yomono</name><affiliations><json:string>Department of Neurology, National Hospital Organization Tokyo Hospital, Tokyo, Japan</json:string></affiliations></json:item><json:item><name>Kuo-Chu Yueh</name><affiliations><json:string>Department of Neurology, Chushang Show-Chwan Hospital, Nantou and Chung-Shan Medical University Hospital, Taichung, Taiwan</json:string></affiliations></json:item><json:item><name>Yi Zhao</name></json:item><json:item><name>Thomas Gasser</name><affiliations><json:string>Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen</json:string></affiliations></json:item><json:item><name>Demetrius Maraganore</name><affiliations><json:string>Department of Neurology, NorthShore University HealthSystem, Chicago, USA</json:string></affiliations></json:item><json:item><name>Rejko Krüger</name><affiliations><json:string>Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Genotype-phenotype correlations</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Open access</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson-s disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Genome-wide</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Genetics</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Genetic epidemiology</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Complex traits</value></json:item></subject><language><json:string>eng</json:string></language><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.</abstract><qualityIndicators><score>6.71</score><pdfVersion>1.3</pdfVersion><pdfPageSize>595.276 x 793.701 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>7</keywordCount><abstractCharCount>1022</abstractCharCount><pdfWordCount>4886</pdfWordCount><pdfCharCount>36557</pdfCharCount><pdfPageCount>6</pdfPageCount><abstractWordCount>152</abstractWordCount></qualityIndicators><title>A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants</title><corporate><json:item><name>on behalf of GEOPD consortium</name></json:item></corporate><genre><json:string>research-article</json:string></genre><host><volume>49</volume><pages><first>721</first></pages><issn><json:string>0022-2593</json:string></issn><issue>11</issue><genre></genre><language><json:string>unknown</json:string></language><eissn><json:string>1468-6244</json:string></eissn><title>Journal of Medical Genetics</title></host><publicationDate>2012</publicationDate><copyrightDate>2012</copyrightDate><doi><json:string>10.1136/jmedgenet-2012-101155</json:string></doi><id>1E80C3110D21541A237742CD339DD00EB1BB056D</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/1E80C3110D21541A237742CD339DD00EB1BB056D/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/1E80C3110D21541A237742CD339DD00EB1BB056D/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/1E80C3110D21541A237742CD339DD00EB1BB056D/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>BMJ Publishing Group Ltd</publisher><availability><p>BMJ</p></availability><date>2012</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants</title><author><orgName>on behalf of GEOPD consortium</orgName></author><author><persName><forename type="first">Manu</forename><surname>Sharma</surname></persName><affiliation>Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen</affiliation></author><author><persName><forename type="first">John P A</forename><surname>Ioannidis</surname></persName><affiliation>Stanford Prevention Research Center, Department of Medicine and Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA</affiliation></author><author><persName><forename type="first">Jan O</forename><surname>Aasly</surname></persName><affiliation>Department of Neurology, St Olavs Hospital and NTNU Trondheim, Trondheim, Norway</affiliation></author><author><persName><forename type="first">Grazia</forename><surname>Annesi</surname></persName><affiliation>Institute of Neurology, Department of Medical Sciences , University Magna Graecia, Catanzaro; Neuroimaging Research Unit, National Research Council, Catanzaro, Italy</affiliation></author><author><persName><forename type="first">Alexis</forename><surname>Brice</surname></persName><affiliation>INSERM, UMR_S975, Université Pierre et Marie Curie-Paris, CNRS, UMR 7225, AP-HP, Pitié-Salpêtriére Hospital</affiliation><affiliation>Cnrs, UMR 7225, Paris, France</affiliation><affiliation>AP-HP, Hôpital Pitié-Salpêtiére, Department of Genetics and Cytogenetics, Paris, France</affiliation></author><author><persName><forename type="first">Lars</forename><surname>Bertram</surname></persName><affiliation>Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.</affiliation></author><author><persName><forename type="first">Maria</forename><surname>Bozi</surname></persName><affiliation>General Hospital of Syros, Syros, Greece</affiliation><affiliation>2nd Neurology Clinic, University of Athens, ‘Attikon’ Hospital, Athens, Greece</affiliation></author><author><persName><forename type="first">Maria</forename><surname>Barcikowska</surname></persName><affiliation>Department of Neurodegenerative Disorders, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland</affiliation></author><author><persName><forename type="first">David</forename><surname>Crosiers</surname></persName><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium</affiliation><affiliation>Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</affiliation><affiliation>Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.</affiliation></author><author><persName><forename type="first">Carl E</forename><surname>Clarke</surname></persName><affiliation>School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, City Hospital, Birmingham, UK</affiliation></author><author><persName><forename type="first">Maurizio F</forename><surname>Facheris</surname></persName><affiliation>Centre for Biomedicine, European Academy Bozen/Bolzano, Itlay, Affiliated institute of the University of Lübeck, Lübeck, German</affiliation></author><author><persName><forename type="first">Matthew</forename><surname>Farrer</surname></persName><affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</affiliation></author><author><persName><forename type="first">Gaetan</forename><surname>Garraux</surname></persName><affiliation>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</affiliation></author><author><persName><forename type="first">Suzana</forename><surname>Gispert</surname></persName><affiliation>Department of Neurology, Goethe University Frankfurt am Main, Frankfurt, Germany</affiliation></author><author><persName><forename type="first">Georg</forename><surname>Auburger</surname></persName><affiliation>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</affiliation></author><author><persName><forename type="first">Carles</forename><surname>Vilariño-Güell</surname></persName><affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</affiliation></author><author><persName><forename type="first">Georgios M</forename><surname>Hadjigeorgiou</surname></persName><affiliation>Department of Neurology, University of Thessaly and Institute of Biomedical Research and Technology, CERETETH, Larissa, Greece</affiliation></author><author><persName><forename type="first">Andrew A</forename><surname>Hicks</surname></persName><affiliation>Centre for Biomedicine, European Academy Bozen/Bolzano, Itlay, Affiliated institute of the University of Lübeck, Lübeck, German</affiliation></author><author><persName><forename type="first">Nobutaka</forename><surname>Hattori</surname></persName><affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan</affiliation></author><author><persName><forename type="first">Beom S</forename><surname>Jeon</surname></persName><affiliation>Department of Neurology, Seoul National University Hospital, Seoul, Korea</affiliation></author><author><persName><forename type="first">Zygmunt</forename><surname>Jamrozik</surname></persName><affiliation>Department of Neurology, Medical University of Warsaw, Warsaw, Poland</affiliation></author><author><persName><forename type="first">Anna</forename><surname>Krygowska-Wajs</surname></persName><affiliation>Department of Neurology, Jagiellonian University, Krakow, Poland</affiliation></author><author><persName><forename type="first">Suzanne</forename><surname>Lesage</surname></persName><affiliation>INSERM, UMR_S975, Université Pierre et Marie Curie-Paris, CNRS, UMR 7225, AP-HP, Pitié-Salpêtriére Hospital</affiliation><affiliation>Cnrs, UMR 7225, Paris, France</affiliation><affiliation>AP-HP, Hôpital Pitié-Salpêtiére, Department of Genetics and Cytogenetics, Paris, France</affiliation></author><author><persName><forename type="first">Christina M</forename><surname>Lill</surname></persName><affiliation>General Hospital of Syros, Syros, Greece</affiliation><affiliation>Department of Neurology, Johannes Gutenberg University, Mainz, Germany</affiliation></author><author><persName><forename type="first">Juei-Jueng</forename><surname>Lin</surname></persName><affiliation>Department of Neurology, Chushang Show-Chwan Hospital, Nantou and Chung-Shan Medical University Hospital, Taichung, Taiwan</affiliation></author><author><persName><forename type="first">Timothy</forename><surname>Lynch</surname></persName><affiliation>The Dublin Neurological Institute at the Mater Misericordiae University Hospital, and Conway Institute, University College Dublin, Dublin, Ireland</affiliation></author><author><persName><forename type="first">Peter</forename><surname>Lichtner</surname></persName><affiliation>Helmholtz Zentrum München, German Research Centre for Environmental Health (Gmbh), Neuherberg, Germany</affiliation></author><author><persName><forename type="first">Anthony E</forename><surname>Lang</surname></persName><affiliation>Movement Disorders Centre, and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Canada</affiliation></author><author><persName><forename type="first">Cecile</forename><surname>Libioulle</surname></persName><affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</affiliation></author><author><persName><forename type="first">Miho</forename><surname>Murata</surname></persName><affiliation>Department of Neurology, National Center Hospital of Neurology and Psychiatry, Tokyo, Japan</affiliation></author><author><persName><forename type="first">Vincent</forename><surname>Mok</surname></persName><affiliation>Department of Medicine and Therapeutics, Prince of Wales Hospital,The Chinese University of Hong Kong, Shatin, Hong Kong</affiliation></author><author><persName><forename type="first">Barbara</forename><surname>Jasinska-Myga</surname></persName><affiliation>Department of Neurology, Medical University of Silesia, Katowice, Poland</affiliation></author><author><persName><forename type="first">George D</forename><surname>Mellick</surname></persName><affiliation>Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Australia</affiliation></author><author><persName><forename type="first">Karen E</forename><surname>Morrison</surname></persName><affiliation>Centre for Biomedicine, European Academy Bozen/Bolzano, Itlay, Affiliated institute of the University of Lübeck, Lübeck, German</affiliation><affiliation>Neurosciences Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK</affiliation></author><author><persName><forename type="first">Thomas</forename><surname>Meitnger</surname></persName><affiliation>German Research Center for Environmental Health, Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany</affiliation><affiliation>Institute of Human Genetics, Technische Universität München, Munich, Germany</affiliation></author><author><persName><forename type="first">Alexander</forename><surname>Zimprich</surname></persName><affiliation>Department of Neurology, Medizinische Universität Wien, Vienna, Austria</affiliation></author><author><persName><forename type="first">Grzegorz</forename><surname>Opala</surname></persName><affiliation>German Research Center for Environmental Health, Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany</affiliation></author><author><persName><forename type="first">Peter P</forename><surname>Pramstaller</surname></persName><affiliation>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</affiliation></author><author><persName><forename type="first">Irene</forename><surname>Pichler</surname></persName><affiliation>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</affiliation></author><author><persName><forename type="first">Sung Sup</forename><surname>Park</surname></persName><affiliation>Department of Neurology, Johannes Gutenberg University, Mainz, Germany</affiliation></author><author><persName><forename type="first">Aldo</forename><surname>Quattrone</surname></persName><affiliation>Institute of Neurology, Department of Medical Sciences , University Magna Graecia, Catanzaro; Neuroimaging Research Unit, National Research Council, Catanzaro, Italy</affiliation></author><author><persName><forename type="first">Ekaterina</forename><surname>Rogaeva</surname></persName><affiliation>Tanz Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Toronto, Canada</affiliation></author><author><persName><forename type="first">Owen A.</forename><surname>Ross</surname></persName><affiliation>Department of Neuroscience, Mayo Clinic, Jacksonville, Florida</affiliation></author><author><persName><forename type="first">Leonidas</forename><surname>Stefanis</surname></persName><affiliation>2nd Neurology Clinic, University of Athens, ‘Attikon’ Hospital, Athens, Greece</affiliation><affiliation>Divisions of Basic Neurosciences & Cell Biology, Biomedical Research Foundation of Academy of Athens, Athens, Greece</affiliation></author><author><persName><forename type="first">Joanne D</forename><surname>Stockton</surname></persName><affiliation>Neurosciences Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK</affiliation></author><author><persName><forename type="first">Wataru</forename><surname>Satake</surname></persName><affiliation>Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan</affiliation></author><author><persName><forename type="first">Peter A</forename><surname>Silburn</surname></persName><affiliation>University of Queensland Centre for Clinical Research, Herston, Australia</affiliation></author><author><persName><forename type="first">Tim M</forename><surname>Strom</surname></persName><affiliation>Institute of Human Genetics, Technische Universität München, Munich, Germany</affiliation><affiliation>Tanz Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Toronto, Canada</affiliation></author><author><persName><forename type="first">Jessie</forename><surname>Theuns</surname></persName><affiliation>Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</affiliation><affiliation>Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.</affiliation></author><author><persName><forename type="first">Eng- King</forename><surname>Tan</surname></persName><affiliation>Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore</affiliation></author><author><persName><forename type="first">Tatsushi</forename><surname>Toda</surname></persName><affiliation>Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan</affiliation></author><author><persName><forename type="first">Hiroyuki</forename><surname>Tomiyama</surname></persName><affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan</affiliation></author><author><persName><forename type="first">Ryan J</forename><surname>Uitti</surname></persName><affiliation>Department of Neurology, Mayo Clinic Jacksonville, USA</affiliation></author><author><persName><forename type="first">Christine</forename><surname>Van Broeckhoven</surname></persName><affiliation>Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</affiliation><affiliation>Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.</affiliation></author><author><persName><forename type="first">Karin</forename><surname>Wirdefeldt</surname></persName><affiliation>Epidemiology and Biostatistics and Department of Clinical Neuroscience, Karolinska Institutet</affiliation></author><author><persName><forename type="first">Zbigniew</forename><surname>Wszolek</surname></persName><affiliation>Department of Neurology, Mayo Clinic Jacksonville, USA</affiliation></author><author><persName><forename type="first">Georgia</forename><surname>Xiromerisiou</surname></persName><affiliation>Department of Neurology, University of Thessaly and Institute of Biomedical Research and Technology, CERETETH, Larissa, Greece</affiliation></author><author><persName><forename type="first">Harumi S</forename><surname>Yomono</surname></persName><affiliation>Department of Neurology, National Hospital Organization Tokyo Hospital, Tokyo, Japan</affiliation></author><author><persName><forename type="first">Kuo-Chu</forename><surname>Yueh</surname></persName><affiliation>Department of Neurology, Chushang Show-Chwan Hospital, Nantou and Chung-Shan Medical University Hospital, Taichung, Taiwan</affiliation></author><author><persName><forename type="first">Yi</forename><surname>Zhao</surname></persName></author><author><persName><forename type="first">Thomas</forename><surname>Gasser</surname></persName><affiliation>Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen</affiliation></author><author><persName><forename type="first">Demetrius</forename><surname>Maraganore</surname></persName><affiliation>Department of Neurology, NorthShore University HealthSystem, Chicago, USA</affiliation></author><author><persName><forename type="first">Rejko</forename><surname>Krüger</surname></persName><affiliation>Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen</affiliation></author></analytic><monogr><title level="j">Journal of Medical Genetics</title><title level="j" type="abbrev">J Med Genet</title><idno type="pISSN">0022-2593</idno><idno type="eISSN">1468-6244</idno><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2012-11"></date><biblScope unit="volume">49</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="721">721</biblScope></imprint></monogr><idno type="istex">1E80C3110D21541A237742CD339DD00EB1BB056D</idno><idno type="DOI">10.1136/jmedgenet-2012-101155</idno><idno type="href">jmedgenet-49-721.pdf</idno><idno type="ArticleID">jmedgenet-2012-101155</idno><idno type="local">jmedgenet;49/11/721</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2012</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>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.</p></abstract><textClass><keywords scheme="keyword"><list><head>hwp-journal-coll</head><item><term>Open access</term></item></list></keywords></textClass><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>Parkinson-s disease</term></item><item><term>Genome-wide</term></item><item><term>Genetics</term></item><item><term>Genetic epidemiology</term></item><item><term>Complex traits</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2012-11">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/1E80C3110D21541A237742CD339DD00EB1BB056D/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus bmj" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="no"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Archiving and Interchange DTD v2.3 20070202//EN" URI="archivearticle.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="hwp">jmedgenet</journal-id><journal-id journal-id-type="nlm-ta">J Med Genet</journal-id><journal-id journal-id-type="publisher-id">jmg</journal-id><journal-title>Journal of Medical Genetics</journal-title><abbrev-journal-title abbrev-type="publisher">J Med Genet</abbrev-journal-title><abbrev-journal-title>J Med Genet</abbrev-journal-title><issn pub-type="ppub">0022-2593</issn><issn pub-type="epub">1468-6244</issn><publisher><publisher-name>BMJ Publishing Group Ltd</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">jmedgenet-2012-101155</article-id><article-id pub-id-type="doi">10.1136/jmedgenet-2012-101155</article-id><article-id pub-id-type="other">jmedgenet;49/11/721</article-id><article-id pub-id-type="other">jmedgenet;jmedgenet-2012-101155</article-id><article-id pub-id-type="other">721</article-id><article-id pub-id-type="other">jmedgenet-2012-101155</article-id><article-categories><subj-group subj-group-type="heading"><subject>Genotype-phenotype correlations</subject></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>Open access</subject></subj-group><series-title>Short report</series-title></article-categories><title-group><article-title>A multi-centre clinico-genetic 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rid="af42">42</xref></contrib><contrib contrib-type="author"><name><surname>Silburn</surname><given-names>Peter A</given-names></name><xref ref-type="aff" rid="af43">43</xref></contrib><contrib contrib-type="author"><name><surname>Strom</surname><given-names>Tim M</given-names></name><xref ref-type="aff" rid="af37">37</xref><xref ref-type="aff" rid="af39">39</xref></contrib><contrib contrib-type="author"><name><surname>Theuns</surname><given-names>Jessie</given-names></name><xref ref-type="aff" rid="af14">14</xref><xref ref-type="aff" rid="af15">15</xref></contrib><contrib contrib-type="author"><name><surname>Tan</surname><given-names>Eng- King</given-names></name><xref ref-type="aff" rid="af44">44</xref></contrib><contrib contrib-type="author"><name><surname>Toda</surname><given-names>Tatsushi</given-names></name><xref ref-type="aff" rid="af42">42</xref></contrib><contrib contrib-type="author"><name><surname>Tomiyama</surname><given-names>Hiroyuki</given-names></name><xref ref-type="aff" rid="af22">22</xref></contrib><contrib contrib-type="author"><name><surname>Uitti</surname><given-names>Ryan J</given-names></name><xref ref-type="aff" rid="af45">45</xref></contrib><contrib contrib-type="author"><name><surname>Van Broeckhoven</surname><given-names>Christine</given-names></name><xref ref-type="aff" rid="af14">14</xref><xref ref-type="aff" rid="af15">15</xref></contrib><contrib contrib-type="author"><name><surname>Wirdefeldt</surname><given-names>Karin</given-names></name><xref ref-type="aff" rid="af46">46</xref></contrib><contrib contrib-type="author"><name><surname>Wszolek</surname><given-names>Zbigniew</given-names></name><xref ref-type="aff" rid="af45">45</xref></contrib><contrib contrib-type="author"><name><surname>Xiromerisiou</surname><given-names>Georgia</given-names></name><xref ref-type="aff" rid="af21">21</xref></contrib><contrib contrib-type="author"><name><surname>Yomono</surname><given-names>Harumi S</given-names></name><xref ref-type="aff" rid="af47">47</xref></contrib><contrib contrib-type="author"><name><surname>Yueh</surname><given-names>Kuo-Chu</given-names></name><xref ref-type="aff" rid="af27">27</xref></contrib><contrib contrib-type="author"><name><surname>Zhao</surname><given-names>Yi</given-names></name></contrib><contrib contrib-type="author"><name><surname>Gasser</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Maraganore</surname><given-names>Demetrius</given-names></name><xref ref-type="aff" rid="af48">48</xref></contrib><contrib contrib-type="author"><name><surname>Krüger</surname><given-names>Rejko</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><collab>on behalf of GEOPD consortium</collab></contrib></contrib-group><aff id="af1"><label>1</label>Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen</aff><aff id="af2"><label>2</label>Stanford Prevention Research Center, Department of Medicine and Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA</aff><aff id="af3"><label>3</label>Department of Neurology, St Olavs Hospital and NTNU Trondheim, Trondheim, Norway</aff><aff id="af4"><label>4</label>Institute of Neurology, Department of Medical Sciences , University Magna Graecia, Catanzaro; Neuroimaging Research Unit, National Research Council, Catanzaro, Italy</aff><aff id="af5"><label>5</label>INSERM, UMR_S975, Université Pierre et Marie Curie-Paris, CNRS, UMR 7225, AP-HP, Pitié-Salpêtriére Hospital</aff><aff id="af6"><label>6</label>Cnrs, UMR 7225, Paris, France</aff><aff id="af7"><label>7</label>AP-HP, Hôpital Pitié-Salpêtiére, Department of Genetics and Cytogenetics, Paris, France</aff><aff id="af8"><label>8</label>Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.</aff><aff id="af9"><label>9</label>General Hospital of Syros, Syros, Greece</aff><aff id="af10"><label>10</label>‘Hygeia’ Hospital, Clinic of Neurodegenerative Disorders, Athens, Greece</aff><aff id="af11"><label>11</label>2nd Neurology Clinic, University of Athens, ‘Attikon’ Hospital, Athens, Greece</aff><aff id="af12"><label>12</label>Department of Neurodegenerative Disorders, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland</aff><aff id="af13"><label>13</label>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium</aff><aff id="af14"><label>14</label>Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</aff><aff id="af15"><label>15</label>Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.</aff><aff id="af16"><label>16</label>School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, City Hospital, Birmingham, UK</aff><aff id="af17"><label>17</label>Centre for Biomedicine, European Academy Bozen/Bolzano, Itlay, Affiliated institute of the University of Lübeck, Lübeck, German</aff><aff id="af18"><label>18</label>Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</aff><aff id="af19"><label>19</label>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</aff><aff id="af20"><label>20</label>Department of Neurology, Goethe University Frankfurt am Main, Frankfurt, Germany</aff><aff id="af21"><label>21</label>Department of Neurology, University of Thessaly and Institute of Biomedical Research and Technology, CERETETH, Larissa, Greece</aff><aff id="af22"><label>22</label>Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan</aff><aff id="af23"><label>23</label>Department of Neurology, Seoul National University Hospital, Seoul, Korea</aff><aff id="af24"><label>24</label>Department of Neurology, Medical University of Warsaw, Warsaw, Poland</aff><aff id="af25"><label>25</label>Department of Neurology, Jagiellonian University, Krakow, Poland</aff><aff id="af26"><label>26</label>Department of Neurology, Johannes Gutenberg University, Mainz, Germany</aff><aff id="af27"><label>27</label>Department of Neurology, Chushang Show-Chwan Hospital, Nantou and Chung-Shan Medical University Hospital, Taichung, Taiwan</aff><aff id="af28"><label>28</label>The Dublin Neurological Institute at the Mater Misericordiae University Hospital, and Conway Institute, University College Dublin, Dublin, Ireland</aff><aff id="af29"><label>29</label>Helmholtz Zentrum München, German Research Centre for Environmental Health (Gmbh), Neuherberg, Germany</aff><aff id="af30"><label>30</label>Movement Disorders Centre, and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Canada</aff><aff id="af31"><label>31</label>Department of Neurology, National Center Hospital of Neurology and Psychiatry, Tokyo, Japan</aff><aff id="af32"><label>32</label>Department of Medicine and Therapeutics, Prince of Wales Hospital,The Chinese University of Hong Kong, Shatin, Hong Kong</aff><aff id="af33"><label>33</label>Department of Neurology, Medical University of Silesia, Katowice, Poland</aff><aff id="af34"><label>34</label>Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Australia</aff><aff id="af35"><label>35</label>Neurosciences Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK</aff><aff id="af36"><label>36</label>German Research Center for Environmental Health, Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany</aff><aff id="af37"><label>37</label>Institute of Human Genetics, Technische Universität München, Munich, Germany</aff><aff id="af38"><label>38</label>Department of Neurology, Medizinische Universität Wien, Vienna, Austria</aff><aff id="af39"><label>39</label>Tanz Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Toronto, Canada</aff><aff id="af40"><label>40</label>Department of Neuroscience, Mayo Clinic, Jacksonville, Florida</aff><aff id="af41"><label>41</label>Divisions of Basic Neurosciences & Cell Biology, Biomedical Research Foundation of Academy of Athens, Athens, Greece</aff><aff id="af42"><label>42</label>Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan</aff><aff id="af43"><label>43</label>University of Queensland Centre for Clinical Research, Herston, Australia</aff><aff id="af44"><label>44</label>Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore</aff><aff id="af45"><label>45</label>Department of Neurology, Mayo Clinic Jacksonville, USA</aff><aff id="af46"><label>46</label>Epidemiology and Biostatistics and Department of Clinical Neuroscience, Karolinska Institutet</aff><aff id="af47"><label>47</label>Department of Neurology, National Hospital Organization Tokyo Hospital, Tokyo, Japan</aff><aff id="af48"><label>48</label>Department of Neurology, NorthShore University HealthSystem, Chicago, USA</aff><author-notes><corresp><label>Correspondence to</label> Dr Manu Sharma, Department. of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen, Hoppe-Seyler-Str. 3, Tübingen 72076, Germany; <email>manu.sharma@uni-tuebingen.de</email></corresp></author-notes><pub-date pub-type="ppub"><month>11</month><year>2012</year></pub-date><volume>49</volume><volume-id pub-id-type="other">49</volume-id><volume-id pub-id-type="other">49</volume-id><issue>11</issue><issue-id pub-id-type="other">jmedgenet;49/11</issue-id><issue-id pub-id-type="other">11</issue-id><issue-id pub-id-type="other">49/11</issue-id><fpage>721</fpage><history><date date-type="received"><day>6</day><month>7</month><year>2012</year></date><date date-type="rev-recd"><day>5</day><month>9</month><year>2012</year></date><date date-type="accepted"><day>7</day><month>9</month><year>2012</year></date></history><permissions><copyright-statement>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</copyright-statement><copyright-year>2012</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</ext-link> and <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/legalcode">http://creativecommons.org/licenses/by-nc/3.0/legalcode</ext-link></p></license></permissions><self-uri content-type="pdf" xlink:role="full-text" xlink:href="jmedgenet-49-721.pdf"></self-uri><abstract><sec><title>Background</title><p>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.</p></sec><sec><title>Methods and results</title><p>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.</p></sec><sec><title>Conclusions</title><p>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.</p></sec></abstract><kwd-group><kwd>Parkinson-s disease</kwd><kwd>Genome-wide</kwd><kwd>Genetics</kwd><kwd>Genetic epidemiology</kwd><kwd>Complex traits</kwd></kwd-group></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><partName>Short report</partName><title>A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><partName>Short report</partName><title>A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants</title></titleInfo><name type="corporate"><namePart>on behalf of GEOPD consortium</namePart></name><name type="personal"><namePart type="given">Manu</namePart><namePart type="family">Sharma</namePart><affiliation>Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John P A</namePart><namePart type="family">Ioannidis</namePart><affiliation>Stanford Prevention Research Center, Department of Medicine and Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jan O</namePart><namePart type="family">Aasly</namePart><affiliation>Department of Neurology, St Olavs Hospital and NTNU Trondheim, Trondheim, Norway</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Grazia</namePart><namePart type="family">Annesi</namePart><affiliation>Institute of Neurology, Department of Medical Sciences , University Magna Graecia, Catanzaro; Neuroimaging Research Unit, National Research Council, Catanzaro, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alexis</namePart><namePart type="family">Brice</namePart><affiliation>INSERM, UMR_S975, Université Pierre et Marie Curie-Paris, CNRS, UMR 7225, AP-HP, Pitié-Salpêtriére Hospital</affiliation><affiliation>Cnrs, UMR 7225, Paris, France</affiliation><affiliation>AP-HP, Hôpital Pitié-Salpêtiére, Department of Genetics and Cytogenetics, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lars</namePart><namePart type="family">Bertram</namePart><affiliation>Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Maria</namePart><namePart type="family">Bozi</namePart><affiliation>General Hospital of Syros, Syros, Greece</affiliation><affiliation>2nd Neurology Clinic, University of Athens, ‘Attikon’ Hospital, Athens, Greece</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Maria</namePart><namePart type="family">Barcikowska</namePart><affiliation>Department of Neurodegenerative Disorders, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">David</namePart><namePart type="family">Crosiers</namePart><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium</affiliation><affiliation>Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</affiliation><affiliation>Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Carl E</namePart><namePart type="family">Clarke</namePart><affiliation>School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, City Hospital, Birmingham, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Maurizio F</namePart><namePart type="family">Facheris</namePart><affiliation>Centre for Biomedicine, European Academy Bozen/Bolzano, Itlay, Affiliated institute of the University of Lübeck, Lübeck, German</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Matthew</namePart><namePart type="family">Farrer</namePart><affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gaetan</namePart><namePart type="family">Garraux</namePart><affiliation>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Suzana</namePart><namePart type="family">Gispert</namePart><affiliation>Department of Neurology, Goethe University Frankfurt am Main, Frankfurt, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Georg</namePart><namePart type="family">Auburger</namePart><affiliation>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Carles</namePart><namePart type="family">Vilariño-Güell</namePart><affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Georgios M</namePart><namePart type="family">Hadjigeorgiou</namePart><affiliation>Department of Neurology, University of Thessaly and Institute of Biomedical Research and Technology, CERETETH, Larissa, Greece</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Andrew A</namePart><namePart type="family">Hicks</namePart><affiliation>Centre for Biomedicine, European Academy Bozen/Bolzano, Itlay, Affiliated institute of the University of Lübeck, Lübeck, German</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nobutaka</namePart><namePart type="family">Hattori</namePart><affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Beom S</namePart><namePart type="family">Jeon</namePart><affiliation>Department of Neurology, Seoul National University Hospital, Seoul, Korea</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Zygmunt</namePart><namePart type="family">Jamrozik</namePart><affiliation>Department of Neurology, Medical University of Warsaw, Warsaw, Poland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anna</namePart><namePart type="family">Krygowska-Wajs</namePart><affiliation>Department of Neurology, Jagiellonian University, Krakow, Poland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Suzanne</namePart><namePart type="family">Lesage</namePart><affiliation>INSERM, UMR_S975, Université Pierre et Marie Curie-Paris, CNRS, UMR 7225, AP-HP, Pitié-Salpêtriére Hospital</affiliation><affiliation>Cnrs, UMR 7225, Paris, France</affiliation><affiliation>AP-HP, Hôpital Pitié-Salpêtiére, Department of Genetics and Cytogenetics, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christina M</namePart><namePart type="family">Lill</namePart><affiliation>General Hospital of Syros, Syros, Greece</affiliation><affiliation>Department of Neurology, Johannes Gutenberg University, Mainz, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Juei-Jueng</namePart><namePart type="family">Lin</namePart><affiliation>Department of Neurology, Chushang Show-Chwan Hospital, Nantou and Chung-Shan Medical University Hospital, Taichung, Taiwan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Timothy</namePart><namePart type="family">Lynch</namePart><affiliation>The Dublin Neurological Institute at the Mater Misericordiae University Hospital, and Conway Institute, University College Dublin, Dublin, Ireland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter</namePart><namePart type="family">Lichtner</namePart><affiliation>Helmholtz Zentrum München, German Research Centre for Environmental Health (Gmbh), Neuherberg, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anthony E</namePart><namePart type="family">Lang</namePart><affiliation>Movement Disorders Centre, and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Cecile</namePart><namePart type="family">Libioulle</namePart><affiliation>Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Miho</namePart><namePart type="family">Murata</namePart><affiliation>Department of Neurology, National Center Hospital of Neurology and Psychiatry, Tokyo, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vincent</namePart><namePart type="family">Mok</namePart><affiliation>Department of Medicine and Therapeutics, Prince of Wales Hospital,The Chinese University of Hong Kong, Shatin, Hong Kong</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Barbara</namePart><namePart type="family">Jasinska-Myga</namePart><affiliation>Department of Neurology, Medical University of Silesia, Katowice, Poland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">George D</namePart><namePart type="family">Mellick</namePart><affiliation>Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Karen E</namePart><namePart type="family">Morrison</namePart><affiliation>Centre for Biomedicine, European Academy Bozen/Bolzano, Itlay, Affiliated institute of the University of Lübeck, Lübeck, German</affiliation><affiliation>Neurosciences Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thomas</namePart><namePart type="family">Meitnger</namePart><affiliation>German Research Center for Environmental Health, Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany</affiliation><affiliation>Institute of Human Genetics, Technische Universität München, Munich, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alexander</namePart><namePart type="family">Zimprich</namePart><affiliation>Department of Neurology, Medizinische Universität Wien, Vienna, Austria</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Grzegorz</namePart><namePart type="family">Opala</namePart><affiliation>German Research Center for Environmental Health, Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter P</namePart><namePart type="family">Pramstaller</namePart><affiliation>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Irene</namePart><namePart type="family">Pichler</namePart><affiliation>Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sung Sup</namePart><namePart type="family">Park</namePart><affiliation>Department of Neurology, Johannes Gutenberg University, Mainz, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Aldo</namePart><namePart type="family">Quattrone</namePart><affiliation>Institute of Neurology, Department of Medical Sciences , University Magna Graecia, Catanzaro; Neuroimaging Research Unit, National Research Council, Catanzaro, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ekaterina</namePart><namePart type="family">Rogaeva</namePart><affiliation>Tanz Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Toronto, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Owen A.</namePart><namePart type="family">Ross</namePart><affiliation>Department of Neuroscience, Mayo Clinic, Jacksonville, Florida</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Leonidas</namePart><namePart type="family">Stefanis</namePart><affiliation>2nd Neurology Clinic, University of Athens, ‘Attikon’ Hospital, Athens, Greece</affiliation><affiliation>Divisions of Basic Neurosciences & Cell Biology, Biomedical Research Foundation of Academy of Athens, Athens, Greece</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Joanne D</namePart><namePart type="family">Stockton</namePart><affiliation>Neurosciences Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Wataru</namePart><namePart type="family">Satake</namePart><affiliation>Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter A</namePart><namePart type="family">Silburn</namePart><affiliation>University of Queensland Centre for Clinical Research, Herston, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Tim M</namePart><namePart type="family">Strom</namePart><affiliation>Institute of Human Genetics, Technische Universität München, Munich, Germany</affiliation><affiliation>Tanz Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Toronto, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jessie</namePart><namePart type="family">Theuns</namePart><affiliation>Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</affiliation><affiliation>Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eng- King</namePart><namePart type="family">Tan</namePart><affiliation>Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Tatsushi</namePart><namePart type="family">Toda</namePart><affiliation>Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hiroyuki</namePart><namePart type="family">Tomiyama</namePart><affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ryan J</namePart><namePart type="family">Uitti</namePart><affiliation>Department of Neurology, Mayo Clinic Jacksonville, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christine</namePart><namePart type="family">Van Broeckhoven</namePart><affiliation>Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</affiliation><affiliation>Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Karin</namePart><namePart type="family">Wirdefeldt</namePart><affiliation>Epidemiology and Biostatistics and Department of Clinical Neuroscience, Karolinska Institutet</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Zbigniew</namePart><namePart type="family">Wszolek</namePart><affiliation>Department of Neurology, Mayo Clinic Jacksonville, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Georgia</namePart><namePart type="family">Xiromerisiou</namePart><affiliation>Department of Neurology, University of Thessaly and Institute of Biomedical Research and Technology, CERETETH, Larissa, Greece</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Harumi S</namePart><namePart type="family">Yomono</namePart><affiliation>Department of Neurology, National Hospital Organization Tokyo Hospital, Tokyo, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kuo-Chu</namePart><namePart type="family">Yueh</namePart><affiliation>Department of Neurology, Chushang Show-Chwan Hospital, Nantou and Chung-Shan Medical University Hospital, Taichung, Taiwan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yi</namePart><namePart type="family">Zhao</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thomas</namePart><namePart type="family">Gasser</namePart><affiliation>Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Demetrius</namePart><namePart type="family">Maraganore</namePart><affiliation>Department of Neurology, NorthShore University HealthSystem, Chicago, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rejko</namePart><namePart type="family">Krüger</namePart><affiliation>Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><subject><genre>hwp-journal-coll</genre><topic>Open access</topic></subject><originInfo><publisher>BMJ Publishing Group Ltd</publisher><dateIssued encoding="w3cdtf">2012-11</dateIssued><copyrightDate encoding="w3cdtf">2012</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><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.</abstract><subject><genre>Keywords</genre><topic>Parkinson-s disease</topic><topic>Genome-wide</topic><topic>Genetics</topic><topic>Genetic epidemiology</topic><topic>Complex traits</topic></subject><relatedItem type="host"><titleInfo><title>Journal of Medical Genetics</title></titleInfo><titleInfo type="abbreviated"><title>J Med Genet</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0022-2593</identifier><identifier type="eISSN">1468-6244</identifier><identifier type="PublisherID">jmg</identifier><identifier type="PublisherID-hwp">jmedgenet</identifier><identifier type="PublisherID-nlm-ta">J Med Genet</identifier><part><date>2012</date><detail type="volume"><caption>vol.</caption><number>49</number></detail><detail type="issue"><caption>no.</caption><number>11</number></detail><extent unit="pages"><start>721</start></extent></part></relatedItem><identifier type="istex">1E80C3110D21541A237742CD339DD00EB1BB056D</identifier><identifier type="DOI">10.1136/jmedgenet-2012-101155</identifier><identifier type="href">jmedgenet-49-721.pdf</identifier><identifier type="ArticleID">jmedgenet-2012-101155</identifier><identifier type="local">jmedgenet;49/11/721</identifier><accessCondition type="use and reproduction" contentType="open-access">This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/3.0/ and http://creativecommons.org/licenses/by-nc/3.0/legalcode</accessCondition><recordInfo><recordContentSource>BMJ</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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