• Johannes R Lemke, Dennis Lal, Eva M Reinthaler, Isabelle Steiner, Michael Nothnagel, Michael Alber, Kirsten Geider, Bodo Laube, Michael Schwake, Katrin Finsterwalder, Andre Franke, Markus Schilhabel, Johanna A Jähn, Hiltrud Muhle, Rainer Boor, Wim Van Paesschen, Roberto Caraballo, Natalio Fejerman, Sarah Weckhuysen, Peter De Jonghe, Jan Larsen, Rikke S Møller, Helle Hjalgrim, Laura Addis, Shan Tang, Elaine Hughes, Deb K Pal, Kadi Veri, Ulvi Vaher, Tiina Talvik, Petia Dimova, Rosa Guerrero López, José M Serratosa, Tarja Linnankivi, Anna-Elina Lehesjoki, Susanne Ruf, Markus Wolff, Sarah Buerki, Gabriele Wohlrab, Judith Kroell, Alexandre N Datta, Barbara Fiedler, Gerhard Kurlemann, Gerhard Kluger, Andreas Hahn, D Edda Haberlandt, Christina Kutzer, Jürgen Sperner, Felicitas Becker, Yvonne G Weber, Martha Feucht, Hannelore Steinböck, Birgit Neophythou, Gabriel M Ronen, Ursula Gruber-Sedlmayr, Julia Geldner, Robert J Harvey, Per Hoffmann, Stefan Herms, Janine Altmüller, Mohammad R Toliat, Holger Thiele, Peter Nürnberg, Christian Wilhelm, Ulrich Stephani, Ingo Helbig, Holger Lerche, Fritz Zimprich, Bernd A Neubauer, Saskia Biskup, and Sarah von Spiczak.
• Division of Human Genetics, University Children's Hospital Inselspital, Bern, Switzerland.
• Nat. Genet. 2013 Sep 1; 45 (9): 1067-72.

AbstractIdiopathic 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.

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