Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes

Item Type:	Article
Title:	Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes
Creators Name:	Lemke, J.R. and Lal, D. and Reinthaler, E.M. and Steiner, I. and Nothnagel, M. and Alber, M. and Geider, K. and Laube, B. and Schwake, M. and Finsterwalder, K. and Franke, A. and Schilhabel, M. and Jähn, J.A. and Muhle, H. and Boor, R. and Van Paesschen, W. and Caraballo, R. and Fejerman, N. and Weckhuysen, S. and De Jonghe, P. and Larsen, J. and Møller, R.S. and Hjalgrim, H. and Addis, L. and Tang, S. and Hughes, E. and Pal, D.K. and Veri, K. and Vaher, U. and Talvik, T. and Dimova, P. and Guerrero López, R. and Serratosa, J.M. and Linnankivi, T. and Lehesjoki, A.E. and Ruf, S. and Wolff, M. and Buerki, S. and Wohlrab, G. and Kroell, J. and Datta, A.N. and Fiedler, B. and Kurlemann, G. and Kluger, G. and Hahn, A. and Haberlandt, D.E. and Kutzer, C. and Sperner, J. and Becker, F. and Weber, Y.G. and Feucht, M. and Steinböck, H. and Neophythou, B. and Ronen, G.M. and Gruber-Sedlmayr, U. and Geldner, J. and Harvey, R.J. and Hoffmann, P. and Herms, S. and Altmüller, J. and Toliat, M.R. and Thiele, H. and Nürnberg, P. and Wilhelm, C. and Stephani, U. and Helbig, I. and Lerche, H. and Zimprich, F. and Neubauer, B.A. and Biskup, S. and von Spiczak, S.
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.
Keywords:	Amino Acid Substitution, Missense Mutation, Molecular Models, Mutation, N-Methyl-D-Aspartate Receptors, Partial Epilepsies, Pedigree, Protein Conformation
Source:	Nature Genetics
ISSN:	1061-4036
Publisher:	Nature Publishing Group
Volume:	45
Number:	9
Page Range:	1067-1072
Date:	September 2013
Official Publication:	https://doi.org/10.1038/ng.2728
PubMed:	View item in PubMed

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