Investigation of GRIN2A in common epilepsy phenotypes

Epilepsy Res. 2015 Sep:115:95-9. doi: 10.1016/j.eplepsyres.2015.05.010. Epub 2015 Jun 2.

Abstract

Recently, mutations and deletions in the GRIN2A gene have been identified to predispose to benign and severe idiopathic focal epilepsies (IFE), revealing a higher incidence of GRIN2A alterations among the more severe phenotypes. This study aimed to explore the phenotypic boundaries of GRIN2A mutations by investigating patients with the two most common epilepsy syndromes: (i) idiopathic generalized epilepsy (IGE) and (ii) temporal lobe epilepsy (TLE). Whole exome sequencing data of 238 patients with IGE as well as Sanger sequencing of 84 patients with TLE were evaluated for GRIN2A sequence alterations. Two additional independent cohorts comprising 1469 IGE and 330 TLE patients were screened for structural deletions (>40kb) involving GRIN2A. Apart from a presumably benign, non-segregating variant in a patient with juvenile absence epilepsy, neither mutations nor deletions were detected in either cohort. These findings suggest that mutations in GRIN2A preferentially are involved in genetic variance of pediatric IFE and do not contribute significantly to either adult focal epilepsies as TLE or generalized epilepsies.

Keywords: Copy number variation; GRIN2A; Idiopathic generalized epilepsy; Mutation; Temporal lobe epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • DNA Copy Number Variations
  • Databases, Genetic
  • Epilepsy, Absence / genetics*
  • Epilepsy, Generalized / genetics*
  • Epilepsy, Temporal Lobe / genetics*
  • Genotyping Techniques
  • Humans
  • Mutation*
  • Phenotype
  • Receptors, N-Methyl-D-Aspartate / genetics*

Substances

  • Receptors, N-Methyl-D-Aspartate
  • N-methyl D-aspartate receptor subtype 2A

Supplementary concepts

  • Epilepsy, Idiopathic Generalized