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Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes.

Lemke, Johannes R. and Lal, Dennis and Reinthaler, Eva M. and Steiner, Isabelle and Nothnagel, Michael and Alber, Michael and Geider, Kirsten and Laube, Bodo and Schwake, Michael and Finsterwalder, Katrin and Franke, Andre and Schilhabel, Markus and Jähn, Johanna A. and Muhle, Hiltrud and Boor, Rainer and Van Paesschen, Wim and Caraballo, Roberto and Fejerman, Natalio and Weckhuysen, Sarah and De Jonghe, Peter and Larsen, Jan and Møller, Rikke S. and Hjalgrim, Helle and Addis, Laura and Tang, Shan and Hughes, Elaine and Pal, Deb K. and Veri, Kadi and Vaher, Ulvi and Talvik, Tiina and Dimova, Petia and Guerrero López, Rosa and Serratosa, José M. and Linnankivi, Tarja and Lehesjoki, Anna-Elina and Ruf, Susanne and Wolff, Markus and Buerki, Sarah and Wohlrab, Gabriele and Kroell, Judith and Datta, Alexandre N. and Fiedler, Barbara and Kurlemann, Gerhard and Kluger, Gerhard and Hahn, Andreas and Haberlandt, D. Edda and Kutzer, Christina and Sperner, Jürgen and Becker, Felicitas and Weber, Yvonne G. and Feucht, Martha and Steinböck, Hannelore and Neophythou, Birgit and Ronen, Gabriel M. and Gruber-Sedlmayr, Ursula and Geldner, Julia and Harvey, Robert J. and Hoffmann, Per and Herms, Stefan and Altmüller, Janine and Toliat, Mohammad R. and Thiele, Holger and Nürnberg, Peter and Wilhelm, Christian and Stephani, Ulrich and Helbig, Ingo and Lerche, Holger and Zimprich, Fritz and Neubauer, Bernd A. and Biskup, Saskia and von Spiczak, Sarah (2013):
Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes.
In: Nature genetics, pp. 1067-72, 45, (9), ISSN 1546-1718,
[Article]

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.

Item Type: Article
Erschienen: 2013
Creators: Lemke, Johannes R. and Lal, Dennis and Reinthaler, Eva M. and Steiner, Isabelle and Nothnagel, Michael and Alber, Michael and Geider, Kirsten and Laube, Bodo and Schwake, Michael and Finsterwalder, Katrin and Franke, Andre and Schilhabel, Markus and Jähn, Johanna A. and Muhle, Hiltrud and Boor, Rainer and Van Paesschen, Wim and Caraballo, Roberto and Fejerman, Natalio and Weckhuysen, Sarah and De Jonghe, Peter and Larsen, Jan and Møller, Rikke S. and Hjalgrim, Helle and Addis, Laura and Tang, Shan and Hughes, Elaine and Pal, Deb K. and Veri, Kadi and Vaher, Ulvi and Talvik, Tiina and Dimova, Petia and Guerrero López, Rosa and Serratosa, José M. and Linnankivi, Tarja and Lehesjoki, Anna-Elina and Ruf, Susanne and Wolff, Markus and Buerki, Sarah and Wohlrab, Gabriele and Kroell, Judith and Datta, Alexandre N. and Fiedler, Barbara and Kurlemann, Gerhard and Kluger, Gerhard and Hahn, Andreas and Haberlandt, D. Edda and Kutzer, Christina and Sperner, Jürgen and Becker, Felicitas and Weber, Yvonne G. and Feucht, Martha and Steinböck, Hannelore and Neophythou, Birgit and Ronen, Gabriel M. and Gruber-Sedlmayr, Ursula and Geldner, Julia and Harvey, Robert J. and Hoffmann, Per and Herms, Stefan and Altmüller, Janine and Toliat, Mohammad R. and Thiele, Holger and Nürnberg, Peter and Wilhelm, Christian and Stephani, Ulrich and Helbig, Ingo and Lerche, Holger and Zimprich, Fritz and Neubauer, Bernd A. and Biskup, Saskia and von Spiczak, Sarah
Title: Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes.
Language: English
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.

Journal or Publication Title: Nature genetics
Volume: 45
Number: 9
Divisions: 10 Department of Biology
10 Department of Biology > Neurophysiology and Neurosensory Systems
Date Deposited: 22 Jan 2015 08:53
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