title: Investigation of GRIN2A in common epilepsy phenotypes.
abstract: Recently, mutations and deletions in the GRIN2A gene have been identified to predispose to benign and severe idiopathic focal epilepsies (IFE), revealing a higher incidence of GRIN2A alterations among the more severe phenotypes. This study aimed to explore the phenotypic boundaries of GRIN2A mutations by investigating patients with the two most common epilepsy syndromes: (i) idiopathic generalized epilepsy (IGE) and (ii) temporal lobe epilepsy (TLE). Whole exome sequencing data of 238 patients with IGE as well as Sanger sequencing of 84 patients with TLE were evaluated for GRIN2A sequence alterations. Two additional independent cohorts comprising 1469 IGE and 330 TLE patients were screened for structural deletions (>40kb) involving GRIN2A. Apart from a presumably benign, non-segregating variant in a patient with juvenile absence epilepsy, neither mutations nor deletions were detected in either cohort. These findings suggest that mutations in GRIN2A preferentially are involved in genetic variance of pediatric IFE and do not contribute significantly to either adult focal epilepsies as TLE or generalized epilepsies.
authors.affiliation: Cologne Center for Genomics, University of Cologne, Cologne, Germany. Electronic address: Dennis.Lal@uni-koeln.de.
authors.forename: Dennis
authors.initials: D
authors.lastname: Lal
authors.affiliation: Division of Human Genetics, University Children's Hospital Inselspital, Bern, Switzerland. Electronic address: s.steinbruecker@gmx.net.
authors.forename: Sandra
authors.initials: S
authors.lastname: Steinbrücker
authors.affiliation: Department of Neurology and Epileptology, Hertie Institute of Clinical Brain Research, University of Tübingen, Tübingen, Germany. Electronic address: julian.schubert@uni-tuebingen.de.
authors.forename: Julian
authors.initials: J
authors.lastname: Schubert
authors.affiliation: Cologne Center for Genomics, University of Cologne, Cologne, Germany. Electronic address: sandert@uni-koeln.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sander
authors.affiliation: Department of Neurology and Epileptology, Hertie Institute of Clinical Brain Research, University of Tübingen, Tübingen, Germany. Electronic address: felicitas.becker@uni-tuebingen.de.
authors.forename: Felicitas
authors.initials: F
authors.lastname: Becker
authors.affiliation: Department of Neurology and Epileptology, Hertie Institute of Clinical Brain Research, University of Tübingen, Tübingen, Germany. Electronic address: yvonne.weber@uni-tuebingen.de.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Weber
authors.affiliation: Department of Neurology and Epileptology, Hertie Institute of Clinical Brain Research, University of Tübingen, Tübingen, Germany. Electronic address: holger.lerche@uni-tuebingen.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Lerche
authors.affiliation: Cologne Center for Genomics, University of Cologne, Cologne, Germany. Electronic address: Holger.Thiele@uni-koeln.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Thiele
authors.affiliation: Luxembourg Centre for Systems Biomedicine, Belval, Luxembourg. Electronic address: roland.krause@uni.lu.
authors.forename: Roland
authors.initials: R
authors.lastname: Krause
authors.affiliation: Folkhälsan Institute of Genetics, Research Program's Unit, Molecular Neurology and Neuroscience Center, University of Helsinki, Helsinki, Finland. Electronic address: anna-elina.lehesjoki@helsinki.fi.
authors.forename: Anna-Elina
authors.initials: AE
authors.lastname: Lehesjoki
authors.affiliation: Cologne Center for Genomics, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. Electronic address: nuernberg@uni-koeln.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge, UK; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland. Electronic address: aarno.palotie@helsinki.fi.
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.affiliation: Department of Neuropediatrics, University Medical Faculty Giessen and Marburg, Giessen, Germany. Electronic address: Bernd.A.Neubauer@paediat.med.uni-giessen.de.
authors.forename: Bernd A
authors.initials: BA
authors.lastname: Neubauer
authors.affiliation: Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel, Germany. Electronic address: Hiltrud.Muhle@uksh.de.
authors.forename: Hiltrud
authors.initials: H
authors.lastname: Muhle
authors.affiliation: Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel, Germany. Electronic address: stephani@pedneuro.uni-kiel.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Stephani
authors.affiliation: Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel, Germany; Children's Hospital of Philadelphia (CHOP), Philadelphia, PA, USA. Electronic address: i.helbig@pedneuro.uni-kiel.de.
authors.forename: Ingo
authors.initials: I
authors.lastname: Helbig
authors.affiliation: Section of Translational Epileptology, Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany. Electronic address: albert_becker@uni-bonn.de.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Becker
authors.affiliation: Section of Translational Epileptology, Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany; Department of Epileptolgoy, University of Bonn Medical Center, Bonn, Germany. Electronic address: susanne.schoch@uni-bonn.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schoch
authors.affiliation: Swiss Epilepsy Center, Zürich, Switzerland. Electronic address: hansen.joerg@bluewin.ch.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hansen
authors.affiliation: Swiss Epilepsy Center, Zürich, Switzerland. Electronic address: Thomas.Dorn@kliniklengg.ch.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dorn
authors.affiliation: Division of Human Genetics, University Children's Hospital Inselspital, Bern, Switzerland. Electronic address: christinhohl@web.de.
authors.forename: Christin
authors.initials: C
authors.lastname: Hohl
authors.affiliation: Division of Human Genetics, University Children's Hospital Inselspital, Bern, Switzerland. Electronic address: n_luescher@yahoo.de.
authors.forename: Nicole
authors.initials: N
authors.lastname: Lüscher
authors.affiliation: Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel, Germany; Northern German Epilepsy Center for Children and Adolescents, Schwentinental-Raisdorf, Germany. Electronic address: s.vonspiczak@pedneuro.uni-kiel.de.
authors.forename: Sarah
authors.initials: S
authors.lastname: von Spiczak
authors.affiliation: Division of Human Genetics, University Children's Hospital Inselspital, Bern, Switzerland; Institute of Human Genetics, University Medical Center Leipzig, Leipzig, Germany. Electronic address: Johannes.Lemke@medizin.uni-leipzig.de.
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Lemke
mesh_terms: D015331:Cohort Studies; D056915:DNA Copy Number Variations; D030541:Databases, Genetic; D004832:Epilepsy, Absence / Q000235:genetics*; D004829:Epilepsy, Generalized / Q000235:genetics*; D004833:Epilepsy, Temporal Lobe / Q000235:genetics*; D060005:Genotyping Techniques; D006801:Humans; D009154:Mutation; D010641:Phenotype; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate
keywords: Copy number variation; GRIN2A; Idiopathic generalized epilepsy; Mutation; Temporal lobe epilepsy