Authors

Dalia Kasperaviciute, NIHR University College London Hospitals
Claudia B Catarino, NIHR University College London Hospitals
Mar Matarin, NIHR University College London Hospitals
Costin Leu, NIHR University College London Hospitals
Jan Novy, NIHR University College London Hospitals
Anna Tostevin, NIHR University College London Hospitals
Bárbara Leal, University of Porto
Ellen V S Hessel, University Medical Centre Utrecht
Kerstin Hallmann, University of Bonn
Michael S Hildebrand, University of Melbourne
Hans-Henrik M Dahl, University of Melbourne
Mina Ryten, UCL Institute of Neurology, London,
Daniah Trabzuni, UCL Institute of Neurology, London,
Adaikalavan Ramasamy, UCL Institute of Neurology, London,
Saud Alhusaini, Royal College of Surgeons in Ireland
Colin P Doherty, St James’ Hospital, Dublin
Thomas Dorn, Swiss Epilepsy Centre
Jörg Hansen, Swiss Epilepsy Centre
Günter Krämer, Swiss Epilepsy Centre
Bernhard J Steinhoff, Kork Epilepsy Centre
Dominik Zumsteg, , University Hospital Zurich
Susan Duncan, Edinburgh and South East Scotland Epilepsy Service
Reetta K Kälviäinen, Kuopio Epilepsy Centre, Kuopio University Hospital
Kai J Eriksson, Paediatric Neurology Unit, Tampere University Hospital and Paediatric Research Centre
Anne-Mari Kantanen, Kuopio Epilepsy Centre, Kuopio University Hospital
Massimo Pandolfo, Hoˆpital Erasme, Universite´ Libre de Bruxelles
Ursula Gruber-Sedlmayr, Medical University of Graz, 8036 Graz, Austria
Kurt Schlachter, Department of Paediatrics, LKH Bregenz, 6900 Bregenz, Austria
Eva M Reinthaler, Medical University of Vienna
Elisabeth Stogmann, Medical University of Vienna
Fritz Zimprich, Medical University of Vienna
Emilie Théâtre, University of Lie`ge, 4000 Lie`ge, Belgium
Colin Smith, University of Edinburgh, Wilkie Building, Edinburgh
Terence J O'Brien, Royal Melbourne Hospital, University of Melbourne
K Meng Tan, Royal Melbourne Hospital, University of Melbourne
Slave Petrovski, Royal Melbourne Hospital, University of Melbourne
Angela Robbiano, University of Genoa
Roberta Paravidino, University of Genoa
Federico Zara, University of Genoa
Pasquale Striano, University of Genoa
Michael R Sperling, Thomas Jefferson UniversityFollow
Russell J Buono, Cooper Medical School of Rowan University
Hakon Hakonarson, The Children’s Hospital of Philadelphia
João Chaves, Hospital Santo António / Centro Hospitalar do Porto, 4099-001 Porto, Portugal
Paulo P Costa, Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA), 4049-019 Porto, Portugal
Berta M Silva, Immunogenetics Laboratory, University of Porto, 4050-313 Porto, Portugal
António M da Silva, Hospital Santo António / Centro Hospitalar do Porto, 4099-001 Porto, Portugal
Pierre N E de Graan, Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Centre Utrecht, 3584 CG Utrecht, The Netherlands
Bobby P C Koeleman, Department of Medical Genetics, University Medical Centre Utrecht, 3584 CG Utrecht, The Netherlands
Albert Becker, Department of Neuropathology, University of Bonn, 53105 Bonn, Germany
Susanne Schoch, Department of Neuropathology, University of Bonn, 53105 Bonn, Germany
Marec von Lehe, Department of Neurosurgery, University of Bochum, 44892 Bochum, Germany
Philipp S Reif, Epilepsy-Centre Hessen, Department of Neurology, University Hospitals and Philipps-University Marburg, 35043 Marburg, Germany
Felix Rosenow, Epilepsy-Centre Hessen, Department of Neurology, University Hospitals and Philipps-University Marburg, 35043 Marburg, Germany
Felicitas Becker, Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany
Yvonne Weber, Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany
Holger Lerche, Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany
Karl Rössler, Department of Neurosurgery, University Hospital Erlangen, 91054 Erlangen, Germany
Michael Buchfelder, Department of Neurosurgery, University Hospital Erlangen, 91054 Erlangen, Germany
Hajo M Hamer, Department of Neurology, Epilepsy Centre, University Hospital Erlangen, 91054 Erlangen, Germany
Katja Kobow, Department of Neuropathology, University Hospital Erlangen, 91054 Erlangen, Germany
Roland Coras, Department of Neuropathology, University Hospital Erlangen, 91054 Erlangen, Germany
Ingmar Blumcke, Department of Neuropathology, University Hospital Erlangen, 91054 Erlangen, Germany
Ingrid E Scheffer, Department of Paediatrics, University of Melbourne, Royal Children’s Hospital, Melbourne VIC 3052, Australia
Samuel F Berkovic, Epilepsy Research Centre, Austin Health, University of Melbourne, Melbourne VIC 3084, Australia
Michael E. Weale, Department of Medical and Molecular Genetics, King’s College London, Guy's Hospital, London, SE1 9RT, UK
UK Brain Expression Consortium, Department of Molecular Neuroscience, UCL Institute of Neurology, London, WC1N 3BG, UK
Norman Delanty, Molecular and Cellular Therapeutics Department, Royal College of Surgeons in Ireland, Dublin 2, Ireland
Chantal Depondt, Department of Neurology, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium
Gianpiero L Cavalleri, Molecular and Cellular Therapeutics Department, Royal College of Surgeons in Ireland, Dublin 2, Ireland
Wolfram S Kunz, Department of Epileptology, University of Bonn, 53105 Bonn, Germany
Sanjay M Sisodiya, NIHR University College London Hospitals

Document Type

Article

Publication Date

10-1-2013

Comments

This article has been peer reviewed. It was published in Brain.

Volume 136, Issue 10, October 2013, Pages 3140-3150.

The published version is available at DOI:10.1093/brain/awt233 . Copyright © Oxford

Abstract

Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10(-9), odds ratio (A) = 1.42, 95% confidence interval: 1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizures.

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