Cell Reports (Jan 2012)
Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions
- Hsien-Yang Lee,
- Yong Huang,
- Nadine Bruneau,
- Patrice Roll,
- Elisha D.O. Roberson,
- Mark Hermann,
- Emily Quinn,
- James Maas,
- Robert Edwards,
- Tetsuo Ashizawa,
- Betul Baykan,
- Kailash Bhatia,
- Susan Bressman,
- Michiko K. Bruno,
- Ewout R. Brunt,
- Roberto Caraballo,
- Bernard Echenne,
- Natalio Fejerman,
- Steve Frucht,
- Christina A. Gurnett,
- Edouard Hirsch,
- Henry Houlden,
- Joseph Jankovic,
- Wei-Ling Lee,
- David R. Lynch,
- Shehla Mohammed,
- Ulrich Müller,
- Mark P. Nespeca,
- David Renner,
- Jacques Rochette,
- Gabrielle Rudolf,
- Shinji Saiki,
- Bing-Wen Soong,
- Kathryn J. Swoboda,
- Sam Tucker,
- Nicholas Wood,
- Michael Hanna,
- Anne M. Bowcock,
- Pierre Szepetowski,
- Ying-Hui Fu,
- Louis J. Ptáček
Affiliations
- Hsien-Yang Lee
- Department of Neurology, UCSF, San Francisco, CA 94158, USA
- Yong Huang
- Department of Neurology, UCSF, San Francisco, CA 94158, USA
- Nadine Bruneau
- Institut de Neurobiologie de la Méditerranée, INMED. Inserm U901. Université de la Méditerranée, 13273 Marseille, Cedex 9, France
- Patrice Roll
- INSERM UMR_S910, Université de la Méditerranée, 13385 Marseille, Cedex 05, France
- Elisha D.O. Roberson
- Division of Human Genetics, Department of Genetics, Washington University School of Medicine, Saint Louis, MO 63110, USA
- Mark Hermann
- Department of Neurology, UCSF, San Francisco, CA 94158, USA
- Emily Quinn
- Department of Neurology, UCSF, San Francisco, CA 94158, USA
- James Maas
- Department of Neurology, UCSF, San Francisco, CA 94158, USA
- Robert Edwards
- Department of Neurology, UCSF, San Francisco, CA 94158, USA
- Tetsuo Ashizawa
- Department of Neurology, University of Florida, Gainesville, FL 32611, USA
- Betul Baykan
- Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Millet Cad 34390, Istanbul, Turkey
- Kailash Bhatia
- Institute of Neurology, University College London, WC1N 3BG London, UK
- Susan Bressman
- Department of Neurology, Beth Israel Medical Center, New York, NY 10003, USA
- Michiko K. Bruno
- Department of Neurology, UCSF, San Francisco, CA 94158, USA
- Ewout R. Brunt
- Department of Neurology, University Medical Centre Groningen, University of Groningen, Groningen, 9713 GZ, The Netherlands
- Roberto Caraballo
- Department of Neurology, Juan P. Garrahan Pediatric Hospital, Combate de los Pozos 1881. CP 1245 Buenos Aires, Argentina
- Bernard Echenne
- Service de Neuropédiatrie, Hôpital Gui de Chauliac, 34295 Montpellier, France
- Natalio Fejerman
- Department of Neurology, Juan P. Garrahan Pediatric Hospital, Combate de los Pozos 1881. CP 1245 Buenos Aires, Argentina
- Steve Frucht
- Movement Disorders Center, Mount Sinai Medical Center, New York, NY 10029, USA
- Christina A. Gurnett
- Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA
- Edouard Hirsch
- Service de Neurologie. Hôpitaux Universitaires de Strasbourg, 67091 Strasbourg, France
- Henry Houlden
- Institute of Neurology, University College London, WC1N 3BG London, UK
- Joseph Jankovic
- Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
- Wei-Ling Lee
- National Neuroscience Institute, 308433 Singapore, Singapore
- David R. Lynch
- Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
- Shehla Mohammed
- Clinical Genetics, Guy's Hospital, SE1 9RT London, UK
- Ulrich Müller
- Institut für Humangenetik, Justus-Liebig-Universität, Giessen, Germany, D-35392
- Mark P. Nespeca
- Pediatric Neurology Division, Rady Children's Hospital San Diego, UCSD Department of Neuroscience, San Diego, CA 92123, USA
- David Renner
- Department of Neurology, University of Utah, Salt Lake City, UT 84132, USA
- Jacques Rochette
- Service de Génétique-INSERM UMR 925, Université de Picardie Jules Verne, Amiens 80036, France
- Gabrielle Rudolf
- Service de Neurologie. Hôpitaux Universitaires de Strasbourg, 67091 Strasbourg, France
- Shinji Saiki
- Department of Neurology, Kanazawa Medical University, Ishikawa 920-0293, Japan
- Bing-Wen Soong
- Department of Neurology, National Yang-Ming University School of Medicine, Taipei 11221, Taiwan
- Kathryn J. Swoboda
- Department of Neurology, University of Utah, Salt Lake City, UT 84132, USA
- Sam Tucker
- Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
- Nicholas Wood
- Institute of Neurology, University College London, WC1N 3BG London, UK
- Michael Hanna
- Institute of Neurology, University College London, WC1N 3BG London, UK
- Anne M. Bowcock
- Division of Human Genetics, Department of Genetics, Washington University School of Medicine, Saint Louis, MO 63110, USA
- Pierre Szepetowski
- Institut de Neurobiologie de la Méditerranée, INMED. Inserm U901. Université de la Méditerranée, 13273 Marseille, Cedex 9, France
- Ying-Hui Fu
- Department of Neurology, UCSF, San Francisco, CA 94158, USA
- Louis J. Ptáček
- Department of Neurology, UCSF, San Francisco, CA 94158, USA
- DOI
- https://doi.org/10.1016/j.celrep.2011.11.001
- Journal volume & issue
-
Vol. 1,
no. 1
pp. 2 – 12
Abstract
Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25) of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.
