Exon-disrupting deletions of NRXN1 in idiopathic generalized epilepsy

Epilepsia. 2013 Feb;54(2):256-64. doi: 10.1111/epi.12078. Epub 2013 Jan 7.


Purpose: Neurexins are neuronal adhesion molecules located in the presynaptic terminal, where they interact with postsynaptic neuroligins to form a transsynaptic complex required for efficient neurotransmission in the brain. Recently, deletions and point mutations of the neurexin 1 (NRXN1) gene have been associated with a broad spectrum of neuropsychiatric disorders. This study aimed to investigate if NRXN1 deletions also increase the risk of idiopathic generalized epilepsies (IGEs).

Methods: We screened for deletions involving the NRXN1 gene in 1,569 patients with IGE and 6,201 controls using high-density oligonucleotide microarrays.

Key findings: We identified exon-disrupting deletions of NRXN1 in 5 of 1,569 patients with IGE and 2 of 6,201 control individuals (p = 0.0049; odds ratio (OR) 9.91, 95% confidence interval (CI) 1.92-51.12). A complex familial segregation pattern in the IGE families was observed, suggesting that heterozygous NRXN1 deletions are susceptibility variants. Intriguingly, we identified a second large copy number variant in three of five index patients, supporting an involvement of heterogeneous susceptibility alleles in the etiology of IGE.

Significance: We conclude that exon-disrupting deletions of NRXN1 represent a genetic risk factor in the genetically complex predisposition of common IGE syndromes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Anticonvulsants / therapeutic use
  • Calcium-Binding Proteins
  • Case-Control Studies
  • Cell Adhesion Molecules, Neuronal / genetics*
  • DNA Copy Number Variations
  • Electroencephalography
  • Epilepsy, Generalized / drug therapy
  • Epilepsy, Generalized / genetics*
  • Epilepsy, Generalized / psychology
  • Exons / genetics*
  • Family
  • Female
  • Fructose / analogs & derivatives
  • Fructose / therapeutic use
  • Gene Deletion
  • Genotype
  • Humans
  • Infant
  • Lamotrigine
  • Male
  • Microarray Analysis
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Neural Cell Adhesion Molecules
  • Neuropsychological Tests
  • Odds Ratio
  • Pedigree
  • Topiramate
  • Triazines / therapeutic use
  • Valproic Acid / therapeutic use


  • Anticonvulsants
  • Calcium-Binding Proteins
  • Cell Adhesion Molecules, Neuronal
  • NRXN1 protein, human
  • Nerve Tissue Proteins
  • Neural Cell Adhesion Molecules
  • Triazines
  • Topiramate
  • Fructose
  • Valproic Acid
  • Lamotrigine