Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes

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Item Type:	Article
Title:	Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes
Creators Name:	Lemke, J.R., Lal, D., Reinthaler, E.M., Steiner, I., Nothnagel, M., Alber, M., Geider, K., Laube, B., Schwake, M., Finsterwalder, K., Franke, A., Schilhabel, M., Jähn, J.A., Muhle, H., Boor, R., Van Paesschen, W., Caraballo, R., Fejerman, N., Weckhuysen, S., De Jonghe, P., Larsen, J., Møller, R.S., Hjalgrim, H., Addis, L., Tang, S., Hughes, E., Pal, D.K., Veri, K., Vaher, U., Talvik, T., Dimova, P., Guerrero López, R., Serratosa, J.M., Linnankivi, T., Lehesjoki, A.E., Ruf, S., Wolff, M., Buerki, S., Wohlrab, G., Kroell, J., Datta, A.N., Fiedler, B., Kurlemann, G., Kluger, G., Hahn, A., Haberlandt, D.E., Kutzer, C., Sperner, J., Becker, F., Weber, Y.G., Feucht, M., Steinböck, H., Neophythou, B., Ronen, G.M., Gruber-Sedlmayr, U., Geldner, J., Harvey, R.J., Hoffmann, P., Herms, S., Altmüller, J., Toliat, M.R., Thiele, H., Nürnberg, P., Wilhelm, C., Stephani, U., Helbig, I., Lerche, H., Zimprich, F., Neubauer, B.A., 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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