Exon‐disrupting deletions of NRXN1 in idiopathic generalized epilepsy. (7th January 2013)

• Record Type: Journal Article
• Authors: Møller, Rikke S.; Weber, Yvonne G.; Klitten, Laura L.; Trucks, Holger; Muhle, Hiltrud; Kunz, Wolfram S.; Mefford, Heather C.; Franke, Andre; Kautza, Monika; Wolf, Peter; Dennig, Dieter; Schreiber, Stefan; Rückert, Ina‐Maria; Wichmann, H.‐Erich; Ernst, Jan P.; Schurmann, Claudia; Grabe, Hans J.; Tommerup, Niels; Stephani, Ulrich; Lerche, Holger; Hjalgrim, Helle; Helbig, Ingo; Sander, Thomas; EPICURE Consortium
• Is Part Of: Epilepsia. Volume 54:issue 2(2013:Feb.)
• Page Start: 256
• Page End: 264
• Publication Date: 2013-01-07
• Subjects: Epilepsy -- Periodicals; 616.853
• DOI: 10.1111/epi.12078
• Languages: English
• ISSNs: 0013-9580

Abstract

<abstract abstract-type="main" id="epi12078-abs-0001"> <title>Summary</title> <sec id="epi12078-sec-0001" sec-type="section"> <title>Purpose</title> <p>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 (<italic>NRXN1</italic>) gene have been associated with a broad spectrum of neuropsychiatric disorders. This study aimed to investigate if <italic>NRXN1</italic> deletions also increase the risk of idiopathic generalized epilepsies (IGEs).</p> </sec> <sec id="epi12078-sec-0002" sec-type="section"> <title>Methods</title> <p>We screened for deletions involving the <italic>NRXN1</italic> gene in 1, 569 patients with IGE and 6, 201 controls using high‐density oligonucleotide microarrays.</p> </sec> <sec id="epi12078-sec-0003" sec-type="section"> <title>Key Findings</title> <p>We identified exon‐disrupting deletions of <italic>NRXN1</italic> 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 <italic>NRXN1</italic> 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.</p> </sec> <sec id="epi12078-sec-0004" sec-type="section"> <title>Significance</title> <p>We conclude that exon‐disrupting deletions of <italic>NRXN1</italic> represent a genetic risk factor in the genetically complex predisposition of common IGE syndromes.</p> </sec> </abstract>