title: Exon-disrupting deletions of NRXN1 in idiopathic generalized epilepsy.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  We conclude that exon-disrupting deletions of NRXN1 represent a genetic risk factor in the genetically complex predisposition of common IGE syndromes.
authors.affiliation: Danish Epilepsy Center, Dianalund, Denmark. rimo@filadelfia.dk
authors.forename: Rikke S
authors.initials: RS
authors.lastname: Møller
authors.forename: Yvonne G
authors.initials: YG
authors.lastname: Weber
authors.forename: Laura L
authors.initials: LL
authors.lastname: Klitten
authors.forename: Holger
authors.initials: H
authors.lastname: Trucks
authors.forename: Hiltrud
authors.initials: H
authors.lastname: Muhle
authors.forename: Wolfram S
authors.initials: WS
authors.lastname: Kunz
authors.forename: Heather C
authors.initials: HC
authors.lastname: Mefford
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.forename: Monika
authors.initials: M
authors.lastname: Kautza
authors.forename: Peter
authors.initials: P
authors.lastname: Wolf
authors.forename: Dieter
authors.initials: D
authors.lastname: Dennig
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Ina-Maria
authors.initials: IM
authors.lastname: Rückert
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Jan P
authors.initials: JP
authors.lastname: Ernst
authors.forename: Claudia
authors.initials: C
authors.lastname: Schurmann
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Grabe
authors.forename: Niels
authors.initials: N
authors.lastname: Tommerup
authors.forename: Ulrich
authors.initials: U
authors.lastname: Stephani
authors.forename: Holger
authors.initials: H
authors.lastname: Lerche
authors.forename: Helle
authors.initials: H
authors.lastname: Hjalgrim
authors.forename: Ingo
authors.initials: I
authors.lastname: Helbig
authors.forename: Thomas
authors.initials: T
authors.lastname: Sander
mesh_terms: D000328:Adult; D017668:Age of Onset; D000927:Anticonvulsants / Q000627:therapeutic use; D002135:Calcium-Binding Proteins; D016022:Case-Control Studies; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D056915:DNA Copy Number Variations; D004569:Electroencephalography; D004829:Epilepsy, Generalized / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology; D005091:Exons / Q000235:genetics*; D005190:Family; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives / Q000627:therapeutic use; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D007223:Infant; D000077213:Lamotrigine; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules; D009483:Neuropsychological Tests; D016017:Odds Ratio; D010375:Pedigree; D000077236:Topiramate; D014227:Triazines / Q000627:therapeutic use; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D014635:Valproic Acid; D000077213:Lamotrigine