Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes

J R Lemke; D Lal; E M Reinthaler; I Steiner; M Nothnagel; M Alber; K Geider; B Laube; M Schwake; K Finsterwalder; A Franke; M Schilhabel; J A Jähn; H Muhle; R Boor; W Van Paesschen; R Caraballo; N Fejerman; S Weckhuysen; P De Jonghe; J Larsen; R S Møller; H Hjalgrim; L Addis; S Tang; E Hughes; D K Pal; K Veri; U Vaher; T Talvik; P Dimova; R Guerrero López; J M Serratosa; T Linnankivi; A E Lehesjoki; S Ruf; M Wolff; S Buerki; G Wohlrab; J Kroell; A N Datta; B Fiedler; G Kurlemann; G Kluger; A Hahn; D E Haberlandt; C Kutzer; J Sperner; F Becker; Y G Weber; M Feucht; H Steinböck; B Neophythou; G M Ronen; U Gruber-Sedlmayr; J Geldner; Robert J Harvey; P Hoffmann; S Herms; J Altmüller; M R Toliat; H Thiele; P Nürnberg; C Wilhelm; U Stephani; I Helbig; H Lerche; F Zimprich; B A Neubauer; S Biskup; S Von Spiczak

doi:10.1038/ng.2728

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Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes

Journal article

Peer reviewed

Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes

J R Lemke, D Lal, E M Reinthaler, I Steiner, M Nothnagel, M Alber, K Geider, B Laube, M Schwake, K Finsterwalder, …

Nature Genetics, Vol.45(9), pp.1067-1072

2013

DOI: https://doi.org/10.1038/ng.2728

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Abstract

Idiopathic focal epilepsy (IFE) with rolandic spikes is the most common childhood epilepsy, comprising a phenotypic spectrum from rolandic epilepsy (also benign epilepsy with centrotemporal spikes, BECTS) to atypical benign partial epilepsy (ABPE), Landau-Kleffner syndrome (LKS) and epileptic encephalopathy with continuous spike and waves during slow-wave sleep (CSWS). The genetic basis is largely unknown. We detected new heterozygous mutations in GRIN2A in 27 of 359 affected individuals from 2 independent cohorts with IFE (7.5%; P = 4.83 × 10 -18, Fisher's exact test). Mutations occurred significantly more frequently in the more severe phenotypes, with mutation detection rates ranging from 12/245 (4.9%) in individuals with BECTS to 9/51 (17.6%) in individuals with CSWS (P = 0.009, Cochran-Armitage test for trend). In addition, exon-disrupting microdeletions were found in 3 of 286 individuals (1.0%; P = 0.004, Fisher's exact test). These results establish alterations of the gene encoding the NMDA receptor NR2A subunit as a major genetic risk factor for IFE.

Details

Title: Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes
Authors: J R Lemke (Author) - University Children's Hospital Inselspital, Switzerland
D Lal (Author) - University of Cologne, Germany
E M Reinthaler (Author) - Medical University of Vienna, Austria
I Steiner (Author) - CeGaT GmbH, Germany
M Nothnagel (Author) - University of Cologne, Germany
M Alber (Author) - University of Tübingen, Germany
K Geider (Author) - Technical University Darmstadt, Germany
B Laube (Author) - Technical University Darmstadt, Germany
M Schwake (Author) - Bielefeld University, Germany
K Finsterwalder (Author) - Christian-Albrecht University, Germany
A Franke (Author) - Christian-Albrecht University, Germany
M Schilhabel (Author) - Christian-Albrecht University, Germany
J A Jähn (Author) - Christian-Albrecht University, Germany
H Muhle (Author) - Christian-Albrecht University, Germany
R Boor (Author) - Christian-Albrecht University, Germany
W Van Paesschen (Author) - University Hospital Leuven, Belgium
R Caraballo (Author) - Juan P. Garrahan Pediatric Hospital, Argentina
N Fejerman (Author) - Juan P. Garrahan Pediatric Hospital, Argentina
S Weckhuysen (Author) - Neurogenetics Group, Belgium
P De Jonghe (Author) - Neurogenetics Group, Belgium
J Larsen (Author) - Danish Epilepsy Center, Denmark
R S Møller (Author) - Danish Epilepsy Center, Denmark
H Hjalgrim (Author) - Danish Epilepsy Center, Denmark
L Addis (Author) - King's College London
S Tang (Author) - King's College London
E Hughes (Author) - King's College London
D K Pal (Author) - King's College London
K Veri (Author) - University of Tartu, Estonia
U Vaher (Author) - University of Tartu, Estonia
T Talvik (Author) - University of Tartu, Estonia
P Dimova (Author) - St. Naum University Hospital, Bulgaria
R Guerrero López (Author) - CIBERER, Spain
J M Serratosa (Author) - CIBERER, Spain
T Linnankivi (Author) - Helsinki University Central Hospital, Finland
A E Lehesjoki (Author) - University of Helsinki, Finland
S Ruf (Author) - University of Tübingen, Germany
M Wolff (Author) - University of Tübingen, Germany
S Buerki (Author) - University Children's Hospital Inselspital, Switzerland
G Wohlrab (Author) - University Children's Hospital Zurich, Switzerland
J Kroell (Author) - Swiss Epilepsy Center, Switzerland
A N Datta (Author) - University Children's Hospital Basel, Switzerland
B Fiedler (Author) - University Medical Center Münster, Germany
G Kurlemann (Author) - University Medical Center Münster, Germany
G Kluger (Author) - Epilepsy Center for Children and Adolescents, Germany
A Hahn (Author) - University Medical Center Giessen and Marburg, Germany
D E Haberlandt (Author) - University Children's Hospital Innsbruck, Austria
C Kutzer (Author) - Kinderzentrum St. Martin, Germany
J Sperner (Author) - Neuropediatric Medical Practice, Germany
F Becker (Author) - University of Tübingen, Germany
Y G Weber (Author) - University of Tübingen, Germany
M Feucht (Author) - Medical University of Vienna, Austria
H Steinböck (Author) - Pediatric Medical Practice, Austria
B Neophythou (Author) - Medical University of Vienna, Austria
G M Ronen (Author) - McMaster University, Canada
U Gruber-Sedlmayr (Author) - Medical University of Graz, Austria
J Geldner (Author) - Hospital Socio-Medical Center, Austria
Robert J Harvey (Author) - University College London, United Kingdom
P Hoffmann (Author) - University of Bonn, Germany
S Herms (Author) - University of Bonn, Germany
J Altmüller (Author) - University of Cologne, Germany
M R Toliat (Author) - University of Cologne, Germany
H Thiele (Author) - University of Cologne, Germany
P Nürnberg (Author) - University of Cologne, Germany
C Wilhelm (Author) - CeGaT GmbH, Germany
U Stephani (Author) - Christian-Albrecht University, Germany
I Helbig (Author) - Christian-Albrecht University, Germany
H Lerche (Author) - University of Tübingen, Germany
F Zimprich (Author) - Medical University of Vienna, Austria
B A Neubauer (Author) - University Medical Center Giessen and Marburg, Germany
S Biskup (Author) - University of Tübingen, Germany
S Von Spiczak (Author) - Christian-Albrecht University, Germany
Publication details: Nature Genetics, Vol.45(9), pp.1067-1072
Publisher: Nature Publishing Group
Date published: 2013
DOI: 10.1038/ng.2728
ISSN: 1061-4036
Organisation Unit: School of Health; School of Health and Sport Sciences - Legacy; Thompson Institute; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99451028502621
Output Type: Journal article

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