You are here

  • Home
  • Archive
  • Volume 49, Issue 11
  • A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants

Article Text

Article menu

This article has a correction. Please see:

Genotype-phenotype correlations
Short report
A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants
  1. Manu Sharma1CA,
  2. John P A Ioannidis2,
  3. Jan O Aasly3,
  4. Grazia Annesi4,
  5. Alexis Brice5,6,7,
  6. Lars Bertram8,
  7. Maria Bozi9,10,11,
  8. Maria Barcikowska12,
  9. David Crosiers13,14,15,
  10. Carl E Clarke16,
  11. Maurizio F Facheris17,
  12. Matthew Farrer18,
  13. Gaetan Garraux19,
  14. Suzana Gispert20,
  15. Georg Auburger19,
  16. Carles Vilariño-Güell18,
  17. Georgios M Hadjigeorgiou21,
  18. Andrew A Hicks17,
  19. Nobutaka Hattori22,
  20. Beom S Jeon23,
  21. Zygmunt Jamrozik24,
  22. Anna Krygowska-Wajs25,
  23. Suzanne Lesage5,6,7,
  24. Christina M Lill9,26,
  25. Juei-Jueng Lin27,
  26. Timothy Lynch28,
  27. Peter Lichtner29,
  28. Anthony E Lang30,
  29. Cecile Libioulle18,
  30. Miho Murata31,
  31. Vincent Mok32,
  32. Barbara Jasinska-Myga33,
  33. George D Mellick34,
  34. Karen E Morrison17,35,
  35. Thomas Meitnger36,37,
  36. Alexander Zimprich38,
  37. Grzegorz Opala36,
  38. Peter P Pramstaller19,
  39. Irene Pichler19,
  40. Sung Sup Park26,
  41. Aldo Quattrone4,
  42. Ekaterina Rogaeva39,
  43. Owen A. Ross40,
  44. Leonidas Stefanis11,41,
  45. Joanne D Stockton35,
  46. Wataru Satake42,
  47. Peter A Silburn43,
  48. Tim M Strom37,39,
  49. Jessie Theuns14,15,
  50. Eng- King Tan44,
  51. Tatsushi Toda42,
  52. Hiroyuki Tomiyama22,
  53. Ryan J Uitti45,
  54. Christine Van Broeckhoven14,15,
  55. Karin Wirdefeldt46,
  56. Zbigniew Wszolek45,
  57. Georgia Xiromerisiou21,
  58. Harumi S Yomono47,
  59. Kuo-Chu Yueh27,
  60. Yi Zhao,
  61. Thomas Gasser1,
  62. Demetrius Maraganore48,
  63. Rejko Krüger1,
  64. on behalf of GEOPD consortium
  1. 1Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen
  2. 2Stanford Prevention Research Center, Department of Medicine and Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA
  3. 3Department of Neurology, St Olavs Hospital and NTNU Trondheim, Trondheim, Norway
  4. 4Institute of Neurology, Department of Medical Sciences , University Magna Graecia, Catanzaro; Neuroimaging Research Unit, National Research Council, Catanzaro, Italy
  5. 5INSERM, UMR_S975, Université Pierre et Marie Curie-Paris, CNRS, UMR 7225, AP-HP, Pitié-Salpêtriére Hospital
  6. 6Cnrs, UMR 7225, Paris, France
  7. 7AP-HP, Hôpital Pitié-Salpêtiére, Department of Genetics and Cytogenetics, Paris, France
  8. 8Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  9. 9General Hospital of Syros, Syros, Greece
  10. 10‘Hygeia’ Hospital, Clinic of Neurodegenerative Disorders, Athens, Greece
  11. 112nd Neurology Clinic, University of Athens, ‘Attikon’ Hospital, Athens, Greece
  12. 12Department of Neurodegenerative Disorders, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
  13. 13Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
  14. 14Institute Born-Bunge, University of Antwerp, Antwerp, Belgium
  15. 15Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.
  16. 16School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, City Hospital, Birmingham, UK
  17. 17Centre for Biomedicine, European Academy Bozen/Bolzano, Itlay, Affiliated institute of the University of Lübeck, Lübeck, German
  18. 18Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
  19. 19Human Genetic Centre, University Hospital of Liége, Liége, Belgium and Department of Neurology, General Central Hospital, Bolzano, Itlay
  20. 20Department of Neurology, Goethe University Frankfurt am Main, Frankfurt, Germany
  21. 21Department of Neurology, University of Thessaly and Institute of Biomedical Research and Technology, CERETETH, Larissa, Greece
  22. 22Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
  23. 23Department of Neurology, Seoul National University Hospital, Seoul, Korea
  24. 24Department of Neurology, Medical University of Warsaw, Warsaw, Poland
  25. 25Department of Neurology, Jagiellonian University, Krakow, Poland
  26. 26Department of Neurology, Johannes Gutenberg University, Mainz, Germany
  27. 27Department of Neurology, Chushang Show-Chwan Hospital, Nantou and Chung-Shan Medical University Hospital, Taichung, Taiwan
  28. 28The Dublin Neurological Institute at the Mater Misericordiae University Hospital, and Conway Institute, University College Dublin, Dublin, Ireland
  29. 29Helmholtz Zentrum München, German Research Centre for Environmental Health (Gmbh), Neuherberg, Germany
  30. 30Movement Disorders Centre, and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Canada
  31. 31Department of Neurology, National Center Hospital of Neurology and Psychiatry, Tokyo, Japan
  32. 32Department of Medicine and Therapeutics, Prince of Wales Hospital,The Chinese University of Hong Kong, Shatin, Hong Kong
  33. 33Department of Neurology, Medical University of Silesia, Katowice, Poland
  34. 34Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Australia
  35. 35Neurosciences Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
  36. 36German Research Center for Environmental Health, Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany
  37. 37Institute of Human Genetics, Technische Universität München, Munich, Germany
  38. 38Department of Neurology, Medizinische Universität Wien, Vienna, Austria
  39. 39Tanz Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Toronto, Canada
  40. 40Department of Neuroscience, Mayo Clinic, Jacksonville, Florida
  41. 41Divisions of Basic Neurosciences & Cell Biology, Biomedical Research Foundation of Academy of Athens, Athens, Greece
  42. 42Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan
  43. 43University of Queensland Centre for Clinical Research, Herston, Australia
  44. 44Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore
  45. 45Department of Neurology, Mayo Clinic Jacksonville, USA
  46. 46Epidemiology and Biostatistics and Department of Clinical Neuroscience, Karolinska Institutet
  47. 47Department of Neurology, National Hospital Organization Tokyo Hospital, Tokyo, Japan
  48. 48Department of Neurology, NorthShore University HealthSystem, Chicago, USA
  1. Correspondence to 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; manu.sharma{at}uni-tuebingen.de

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.

  • Parkinson-s disease
  • Genome-wide
  • Genetics
  • Genetic epidemiology
  • Complex traits

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

https://doi.org/10.1136/jmedgenet-2012-101155

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Supplementary materials

    • Supplementary Data

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

      Files in this Data Supplement:

    Linked Articles

    • Correction
      Correction
      BMJ Publishing Group Ltd
      Journal of Medical Genetics 2013; 50 202-202 Published Online First: 13 Feb 2013. doi: 10.1136/jmedgenet-2012-101155corr1