Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes Academic Article uri icon

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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.

authors

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

publication date

  • September 2013