|
Title
|
|
|
|
Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes
| |
|
Author
|
|
|
|
| |
|
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)(1,2). 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 x 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. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Nature genetics. - New York, N.Y.
| |
|
Publication
|
|
|
|
New York, N.Y.
:
2013
| |
|
ISSN
|
|
|
|
1061-4036
| |
|
DOI
|
|
|
|
10.1038/NG.2728
| |
|
Volume/pages
|
|
|
|
45
:9
(2013)
, p. 1067-+
| |
|
ISI
|
|
|
|
000323748200018
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|