2. Academic Validation
  3. Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes

Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes

  • Nat Genet. 2013 Sep;45(9):1067-72. doi: 10.1038/ng.2728.
Johannes R Lemke 1,  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,  Sarah von Spiczak
Affiliations

Affiliation

  • 1 Division of Human Genetics, University Children's Hospital Inselspital, Bern, Switzerland.
PMID: 23933819 DOI: 10.1038/ng.2728
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.

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