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A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants
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 pe...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
BMJ Publishing Group
2012
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488700/ https://www.ncbi.nlm.nih.gov/pubmed/23125461 http://dx.doi.org/10.1136/jmedgenet-2012-101155 |
| _version_ | 1782248661598601216 |
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| author | Sharma, Manu Ioannidis, John P A Aasly, Jan O Annesi, Grazia Brice, Alexis Bertram, Lars Bozi, Maria Barcikowska, Maria Crosiers, David Clarke, Carl E Facheris, Maurizio F Farrer, Matthew Garraux, Gaetan Gispert, Suzana Auburger, Georg Vilariño-Güell, Carles Hadjigeorgiou, Georgios M Hicks, Andrew A Hattori, Nobutaka Jeon, Beom S Jamrozik, Zygmunt Krygowska-Wajs, Anna Lesage, Suzanne Lill, Christina M Lin, Juei-Jueng Lynch, Timothy Lichtner, Peter Lang, Anthony E Libioulle, Cecile Murata, Miho Mok, Vincent Jasinska-Myga, Barbara Mellick, George D Morrison, Karen E Meitnger, Thomas Zimprich, Alexander Opala, Grzegorz Pramstaller, Peter P Pichler, Irene Park, Sung Sup Quattrone, Aldo Rogaeva, Ekaterina Ross, Owen A. Stefanis, Leonidas Stockton, Joanne D Satake, Wataru Silburn, Peter A Strom, Tim M Theuns, Jessie Tan, Eng- King Toda, Tatsushi Tomiyama, Hiroyuki Uitti, Ryan J Van Broeckhoven, Christine Wirdefeldt, Karin Wszolek, Zbigniew Xiromerisiou, Georgia Yomono, Harumi S Yueh, Kuo-Chu Zhao, Yi Gasser, Thomas Maraganore, Demetrius Krüger, Rejko |
| author_facet | Sharma, Manu Ioannidis, John P A Aasly, Jan O Annesi, Grazia Brice, Alexis Bertram, Lars Bozi, Maria Barcikowska, Maria Crosiers, David Clarke, Carl E Facheris, Maurizio F Farrer, Matthew Garraux, Gaetan Gispert, Suzana Auburger, Georg Vilariño-Güell, Carles Hadjigeorgiou, Georgios M Hicks, Andrew A Hattori, Nobutaka Jeon, Beom S Jamrozik, Zygmunt Krygowska-Wajs, Anna Lesage, Suzanne Lill, Christina M Lin, Juei-Jueng Lynch, Timothy Lichtner, Peter Lang, Anthony E Libioulle, Cecile Murata, Miho Mok, Vincent Jasinska-Myga, Barbara Mellick, George D Morrison, Karen E Meitnger, Thomas Zimprich, Alexander Opala, Grzegorz Pramstaller, Peter P Pichler, Irene Park, Sung Sup Quattrone, Aldo Rogaeva, Ekaterina Ross, Owen A. Stefanis, Leonidas Stockton, Joanne D Satake, Wataru Silburn, Peter A Strom, Tim M Theuns, Jessie Tan, Eng- King Toda, Tatsushi Tomiyama, Hiroyuki Uitti, Ryan J Van Broeckhoven, Christine Wirdefeldt, Karin Wszolek, Zbigniew Xiromerisiou, Georgia Yomono, Harumi S Yueh, Kuo-Chu Zhao, Yi Gasser, Thomas Maraganore, Demetrius Krüger, Rejko |
| author_sort | Sharma, Manu |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-3488700 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2012 |
| publisher | BMJ Publishing Group |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-34887002012-11-07 A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants Sharma, Manu Ioannidis, John P A Aasly, Jan O Annesi, Grazia Brice, Alexis Bertram, Lars Bozi, Maria Barcikowska, Maria Crosiers, David Clarke, Carl E Facheris, Maurizio F Farrer, Matthew Garraux, Gaetan Gispert, Suzana Auburger, Georg Vilariño-Güell, Carles Hadjigeorgiou, Georgios M Hicks, Andrew A Hattori, Nobutaka Jeon, Beom S Jamrozik, Zygmunt Krygowska-Wajs, Anna Lesage, Suzanne Lill, Christina M Lin, Juei-Jueng Lynch, Timothy Lichtner, Peter Lang, Anthony E Libioulle, Cecile Murata, Miho Mok, Vincent Jasinska-Myga, Barbara Mellick, George D Morrison, Karen E Meitnger, Thomas Zimprich, Alexander Opala, Grzegorz Pramstaller, Peter P Pichler, Irene Park, Sung Sup Quattrone, Aldo Rogaeva, Ekaterina Ross, Owen A. Stefanis, Leonidas Stockton, Joanne D Satake, Wataru Silburn, Peter A Strom, Tim M Theuns, Jessie Tan, Eng- King Toda, Tatsushi Tomiyama, Hiroyuki Uitti, Ryan J Van Broeckhoven, Christine Wirdefeldt, Karin Wszolek, Zbigniew Xiromerisiou, Georgia Yomono, Harumi S Yueh, Kuo-Chu Zhao, Yi Gasser, Thomas Maraganore, Demetrius Krüger, Rejko J Med Genet Genotype-Phenotype Correlations 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. BMJ Publishing Group 2012-11 /pmc/articles/PMC3488700/ /pubmed/23125461 http://dx.doi.org/10.1136/jmedgenet-2012-101155 Text en 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 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 |
| spellingShingle | Genotype-Phenotype Correlations Sharma, Manu Ioannidis, John P A Aasly, Jan O Annesi, Grazia Brice, Alexis Bertram, Lars Bozi, Maria Barcikowska, Maria Crosiers, David Clarke, Carl E Facheris, Maurizio F Farrer, Matthew Garraux, Gaetan Gispert, Suzana Auburger, Georg Vilariño-Güell, Carles Hadjigeorgiou, Georgios M Hicks, Andrew A Hattori, Nobutaka Jeon, Beom S Jamrozik, Zygmunt Krygowska-Wajs, Anna Lesage, Suzanne Lill, Christina M Lin, Juei-Jueng Lynch, Timothy Lichtner, Peter Lang, Anthony E Libioulle, Cecile Murata, Miho Mok, Vincent Jasinska-Myga, Barbara Mellick, George D Morrison, Karen E Meitnger, Thomas Zimprich, Alexander Opala, Grzegorz Pramstaller, Peter P Pichler, Irene Park, Sung Sup Quattrone, Aldo Rogaeva, Ekaterina Ross, Owen A. Stefanis, Leonidas Stockton, Joanne D Satake, Wataru Silburn, Peter A Strom, Tim M Theuns, Jessie Tan, Eng- King Toda, Tatsushi Tomiyama, Hiroyuki Uitti, Ryan J Van Broeckhoven, Christine Wirdefeldt, Karin Wszolek, Zbigniew Xiromerisiou, Georgia Yomono, Harumi S Yueh, Kuo-Chu Zhao, Yi Gasser, Thomas Maraganore, Demetrius Krüger, Rejko A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants |
| title | A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants |
| title_full | A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants |
| title_fullStr | A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants |
| title_full_unstemmed | A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants |
| title_short | A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants |
| title_sort | multi-centre clinico-genetic analysis of the vps35 gene in parkinson disease indicates reduced penetrance for disease-associated variants |
| topic | Genotype-Phenotype Correlations |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488700/ https://www.ncbi.nlm.nih.gov/pubmed/23125461 http://dx.doi.org/10.1136/jmedgenet-2012-101155 |
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