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16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy

Reinthaler, Eva M. ; Lal, Dennis ; Lebon, Sebastien ; Hildebrand, Michael S. ; Dahl, Hans-Henrik M. ; Regan, Brigid M. ; Feucht, Martha ; Steinböck, Hannelore ; Neophytou, Birgit ; Ronen, Gabriel M. ; Roche, Laurian ; Gruber-Sedlmayr, Ursula ; Geldner, Julia ; Haberlandt, Edda ; Hoffmann, Per ; Herms, Stefan ; Gieger, Christian ; Waldenberger, Melanie ; Franke, Andre ; Wittig, Michael ; Schoch, Susanne ; Becker, Albert J. ; Hahn, Andreas ; Männik, Katrin ; Toliat, Mohammad R. ; Winterer, Georg ; Lerche, Holger ; Nürnberg, Peter ; Mefford, Heather ; Scheffer, Ingrid E. ; Berkovic, Samuel F. ; Beckmann, Jacques S. ; Sander, Thomas ; Jacquemont, Sebastien ; Reymond, Alexandre ; Zimprich, Fritz ; Neubauer, Bernd A. ; Reinthaler, Eva M. ; Zimprich, Fritz ; Feucht, Martha ; Steinböck, Hannelore ; Neophytou, Birgit ; Geldner, Julia ; Gruber-Sedlmayr, Ursula ; Haberlandt, Edda ; Ronen, Gabriel M. ; Roche, Laurian ; Lal, Dennis ; Nürnberg, Peter ; Sander, Thomas ; Lerche, Holger ; Neubauer, Bernd ; Mörzinger, Martina ; Suls, Arvid ; Weckhuysen, Sarah ; Claes, Lieve ; Deprez, Liesbet ; Smets, Katrien ; Van Dyck, Tine ; Deconinck, Tine ; De Jonghe, Peter ; Møller, Rikke S. ; Klitten, Laura L. ; Hjalgrim, Helle ; Campus, Kiel ; Helbig, Ingo ; Muhle, Hiltrud ; Ostertag, Philipp ; von Spiczak, Sarah ; Stephani, Ulrich ; Trucks, Holger ; Elger, Christian E. ; Kleefuß-Lie, Ailing A. ; Kunz, Wolfram S. ; Surges, Rainer ; Gaus, Verena ; Janz, Dieter ; Schmitz, Bettina ; Rosenow, Felix ; Klein, Karl Martin ; Reif, Philipp S. ; Oertel, Wolfgang H. ; Hamer, Hajo M. ; Becker, Felicitas ; Weber, Yvonne ; Koeleman, Bobby P.C. ; de Kovel, Carolien ; Lindhout, Dick ; Ameil, Agnès ; Andrieux, Joris ; Bouquillon, Sonia ; Boute, Odile ; de Flandre, Jeanne ; Cuisset, Jean Marie ; Cuvellier, Jean-Christophe ; Salengro, Roger ; David, Albert ; de Vries, Bert ; Delrue, Marie-Ange ; Doco-Fenzy, Martine ; Fernandez, Bridget A. ; Heron, Delphine ; Keren, Boris ; Lebel, Robert ; Leheup, Bruno ; Lewis, Suzanne ; Mencarelli, Maria Antonietta ; Mignot, Cyril ; Minet, Jean-Claude ; Moerman, Alexandre ; Morice-Picard, Fanny ; Mucciolo, Mafalda ; Ounap, Katrin ; Pasquier, Laurent ; Petit, Florence ; Ragona, Francesca ; Rajcan-Separovic, Evica ; Renieri, Alessandra ; Rieubland, Claudine ; Sanlaville, Damien ; Sarrazin, Elisabeth ; Shen, Yiping ; van Haelst, Mieke ; Silfhout, Anneke Vulto-van

In: Human Molecular Genetics, 2014, vol. 23, no. 22, p. 6069-6080

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    Titre
    • 16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy
    Auteur
    • Reinthaler, Eva M.. Department of Neurology
    • Lal, Dennis. Cologne Center for Genomics
    • Lebon, Sebastien. Unit of Pediatric Neurology and Neurorehabilitation, Department of Pediatrics
    • Hildebrand, Michael S.. Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Australia
    • Dahl, Hans-Henrik M.. Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Australia
    • Regan, Brigid M.. Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Australia
    • Feucht, Martha. Department of Pediatrics, Medical University of Vienna, Vienna, Austria
    • Steinböck, Hannelore. Private Practice for Pediatrics, Vienna, Austria
    • Neophytou, Birgit. Department of Neuropediatrics, St. Anna Children's Hospital, Vienna, Austria
    • Ronen, Gabriel M.. Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
    • Roche, Laurian. Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
    • Gruber-Sedlmayr, Ursula. Department of Pediatrics, Medical University of Graz, Graz, Austria
    • Geldner, Julia. Department of Pediatrics, Hospital SMZ Süd Kaiser-Franz-Josef Spital, Vienna, Austria
    • Haberlandt, Edda. Department of Pediatrics, Medical University of Innsbruck, Innsbruck, Austria
    • Hoffmann, Per. Institute of Human Genetics, University of Bonn, Bonn, Germany
    • Herms, Stefan. Institute of Human Genetics, University of Bonn, Bonn, Germany
    • Gieger, Christian. Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Institute of Genetic Epidemiology, Neuherberg, Germany
    • Waldenberger, Melanie. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
    • Franke, Andre. Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
    • Wittig, Michael. Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
    • Schoch, Susanne. Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany
    • Becker, Albert J.. Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany
    • Hahn, Andreas. Department of Neuropediatrics, University Medical Faculty Giessen and Marburg, Giessen, Germany
    • Männik, Katrin. Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
    • Toliat, Mohammad R.. Cologne Center for Genomics
    • Winterer, Georg. Experimental and Clinical Research Center (ECRC) Charité, University Medicine Berlin, Berlin, Germany
    • Lerche, Holger. Department of Neurology and Epileptology, Hertie Institute of Clinical Brain Research, University of Tübingen, Tübingen, Germany
    • Nürnberg, Peter. Cologne Center for Genomics
    • Mefford, Heather. Division of Genetic Medicine, University of Washington, Seattle, Washington, USA
    • Scheffer, Ingrid E.. Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Australia
    • Berkovic, Samuel F.. Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Australia
    • Beckmann, Jacques S.. Service of Medical Genetics, Lausanne University Hospital, Lausanne, Switzerland
    • Sander, Thomas. Cologne Center for Genomics
    • Jacquemont, Sebastien. Service of Medical Genetics, Lausanne University Hospital, Lausanne, Switzerland
    • Reymond, Alexandre. Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
    • Zimprich, Fritz. Department of Neurology
    • Neubauer, Bernd A.. Department of Neuropediatrics, University Medical Faculty Giessen and Marburg, Giessen, Germany
    • Reinthaler, Eva M.
    • Zimprich, Fritz
    • Feucht, Martha
    • Steinböck, Hannelore
    • Neophytou, Birgit
    • Geldner, Julia
    • Gruber-Sedlmayr, Ursula
    • Haberlandt, Edda
    • Ronen, Gabriel M.
    • Roche, Laurian
    • Lal, Dennis
    • Nürnberg, Peter
    • Sander, Thomas
    • Lerche, Holger
    • Neubauer, Bernd
    • Mörzinger, Martina
    • Suls, Arvid
    • Weckhuysen, Sarah
    • Claes, Lieve
    • Deprez, Liesbet
    • Smets, Katrien
    • Van Dyck, Tine
    • Deconinck, Tine
    • De Jonghe, Peter
    • Møller, Rikke S.
    • Klitten, Laura L.
    • Hjalgrim, Helle
    • Campus, Kiel
    • Helbig, Ingo
    • Muhle, Hiltrud
    • Ostertag, Philipp
    • von Spiczak, Sarah
    • Stephani, Ulrich
    • Trucks, Holger
    • Elger, Christian E.
    • Kleefuß-Lie, Ailing A.
    • Kunz, Wolfram S.
    • Surges, Rainer
    • Gaus, Verena
    • Janz, Dieter
    • Schmitz, Bettina
    • Rosenow, Felix
    • Klein, Karl Martin
    • Reif, Philipp S.
    • Oertel, Wolfgang H.
    • Hamer, Hajo M.
    • Becker, Felicitas
    • Weber, Yvonne
    • Koeleman, Bobby P.C.
    • de Kovel, Carolien
    • Lindhout, Dick
    • Ameil, Agnès
    • Andrieux, Joris
    • Bouquillon, Sonia
    • Boute, Odile
    • de Flandre, Jeanne
    • Cuisset, Jean Marie
    • Cuvellier, Jean-Christophe
    • Salengro, Roger
    • David, Albert
    • de Vries, Bert
    • Delrue, Marie-Ange
    • Doco-Fenzy, Martine
    • Fernandez, Bridget A.
    • Heron, Delphine
    • Keren, Boris
    • Lebel, Robert
    • Leheup, Bruno
    • Lewis, Suzanne
    • Mencarelli, Maria Antonietta
    • Mignot, Cyril
    • Minet, Jean-Claude
    • Moerman, Alexandre
    • Morice-Picard, Fanny
    • Mucciolo, Mafalda
    • Ounap, Katrin
    • Pasquier, Laurent
    • Petit, Florence
    • Ragona, Francesca
    • Rajcan-Separovic, Evica
    • Renieri, Alessandra
    • Rieubland, Claudine
    • Sanlaville, Damien
    • Sarrazin, Elisabeth
    • Shen, Yiping
    • van Haelst, Mieke
    • Silfhout, Anneke Vulto-van
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • Human Molecular Genetics, 2014, vol. 23, no. 22, p. 6069-6080. Oxford University Press
    Autre version électronique
    Classification
    • Santé
    Identifiant OAI-PMH
    • oai:doc.rero.ch:291490
    Summary
    Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 × 10−6, odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10−4). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical RE