Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes
Copyright policy )Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes
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.
- McMaster University Canada
- Justus Liebig University Giessen Germany
- Wiener Krankenanstaltenverbund Austria
- Schön Klinik Vogtareuth Germany
- Katholieke Universiteit Leuven Belgium
Male, Models, Molecular, Protein Conformation, Mutation, Missense, 610, 610 Medicine & health, Epilepsies, Receptors, N-Methyl-D-Aspartate, diagnosis [Epilepsies, Partial], genetics [Epilepsies, Partial], 1311 Genetics, Models, 616, Receptors, genetics [Receptors, N-Methyl-D-Aspartate], Humans, chemistry [Receptors, N-Methyl-D-Aspartate], metabolism [Receptors, N-Methyl-D-Aspartate], Molecular, N-methyl D-aspartate receptor subtype 2A, Pedigree, Amino Acid Substitution, 10036 Medical Clinic, Mutation, Female, Epilepsies, Partial, Missense, Partial, N-Methyl-D-Aspartate, ddc: ddc:570
Male, Models, Molecular, Protein Conformation, Mutation, Missense, 610, 610 Medicine & health, Epilepsies, Receptors, N-Methyl-D-Aspartate, diagnosis [Epilepsies, Partial], genetics [Epilepsies, Partial], 1311 Genetics, Models, 616, Receptors, genetics [Receptors, N-Methyl-D-Aspartate], Humans, chemistry [Receptors, N-Methyl-D-Aspartate], metabolism [Receptors, N-Methyl-D-Aspartate], Molecular, N-methyl D-aspartate receptor subtype 2A, Pedigree, Amino Acid Substitution, 10036 Medical Clinic, Mutation, Female, Epilepsies, Partial, Missense, Partial, N-Methyl-D-Aspartate, ddc: ddc:570
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