{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:12:35Z","timestamp":1791349955533,"version":"4.3.1"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,1,7]],"date-time":"2013-01-07T00:00:00Z","timestamp":1357516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats: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 (<jats:styled-content style=\"fixed-case\"><jats:italic>NRXN1<\/jats:italic><\/jats:styled-content>) gene have been associated with a broad spectrum of neuropsychiatric disorders. This study aimed to investigate if <jats:styled-content style=\"fixed-case\"><jats:italic>NRXN1<\/jats:italic><\/jats:styled-content> deletions also increase the risk of idiopathic generalized epilepsies (<jats:styled-content style=\"fixed-case\">IGE<\/jats:styled-content>s).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We screened for deletions involving the <jats:styled-content style=\"fixed-case\"><jats:italic>NRXN1<\/jats:italic><\/jats:styled-content> gene in 1,569 patients with <jats:styled-content style=\"fixed-case\">IGE<\/jats:styled-content> and 6,201 controls using high\u2010density oligonucleotide microarrays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Findings<\/jats:title><jats:p>We identified exon\u2010disrupting deletions of <jats:styled-content style=\"fixed-case\"><jats:italic>NRXN1<\/jats:italic><\/jats:styled-content> in 5 of 1,569 patients with <jats:styled-content style=\"fixed-case\">IGE<\/jats:styled-content> and 2 of 6,201 control individuals (p\u00a0=\u00a00.0049; odds ratio (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>)\u00a09.91, 95% confidence interval (<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>) 1.92\u201351.12). A complex familial segregation pattern in the <jats:styled-content style=\"fixed-case\">IGE<\/jats:styled-content> families was observed, suggesting that heterozygous <jats:styled-content style=\"fixed-case\"><jats:italic>NRXN1<\/jats:italic><\/jats:styled-content> 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 <jats:styled-content style=\"fixed-case\">IGE<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>We conclude that exon\u2010disrupting deletions of <jats:styled-content style=\"fixed-case\"><jats:italic>NRXN1<\/jats:italic><\/jats:styled-content> represent a genetic risk factor in the genetically complex predisposition of common <jats:styled-content style=\"fixed-case\">IGE<\/jats:styled-content> syndromes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12078","type":"journal-article","created":{"date-parts":[[2013,1,7]],"date-time":"2013-01-07T14:15:08Z","timestamp":1357568108000},"page":"256-264","source":"Crossref","is-referenced-by-count":66,"title":["Exon\u2010disrupting deletions of <scp><i>NRXN1<\/i><\/scp> in idiopathic generalized epilepsy"],"prefix":"10.1111","volume":"54","author":[{"given":"Rikke S.","family":"M\u00f8ller","sequence":"first","affiliation":[{"name":"Danish Epilepsy Center Dianalund Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne G.","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Neurology and Epileptology Hertie Institute for Clinical Brain Research University Hospital T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L.","family":"Klitten","sequence":"additional","affiliation":[{"name":"Danish Epilepsy Center Dianalund Denmark"},{"name":"Wilhelm Johannsen Center for Functional Genome Research University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Trucks","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiltrud","family":"Muhle","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics University Medical Center Schleswig\u2010Holstein Christian\u2010Albrechts University Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfram S.","family":"Kunz","sequence":"additional","affiliation":[{"name":"Department of Epileptology University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather C.","family":"Mefford","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Department of Pediatrics University of Washington Seattle Washington U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Franke","sequence":"additional","affiliation":[{"name":"Institute for Clinical Molecular Biology University Hospital Schleswig\u2010Holstein Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Kautza","sequence":"additional","affiliation":[{"name":"Praxis of Human Genetics Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Wolf","sequence":"additional","affiliation":[{"name":"Danish Epilepsy Center Dianalund Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Dennig","sequence":"additional","affiliation":[{"name":"Neurological Practice \u201cAm Seelberg\u201d Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Institute for Clinical Molecular Biology University Hospital Schleswig\u2010Holstein Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina\u2010Maria","family":"R\u00fcckert","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology II Helmholtz Zentrum M\u00fcnchen \u2013 German Research Center for Environmental Health Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.\u2010Erich","family":"Wichmann","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology II Helmholtz Zentrum M\u00fcnchen \u2013 German Research Center for Environmental Health Neuherberg Germany"},{"name":"Institute of Medical Informatics, Biometry and Epidemiology Chair of Epidemiology Ludwig\u2010Maximilians\u2010Universit\u00e4t Munich Germany"},{"name":"Klinikum Grosshadern Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan P.","family":"Ernst","sequence":"additional","affiliation":[{"name":"Pediatric Practice Oggersheim Ludwigshafer Germany"},{"name":"Epilepsy Centre Kork Kehl Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Schurmann","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Genetics and Functional Genomics Ernst\u2010Moritz\u2010Arndt\u2010University Greifswald Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J.","family":"Grabe","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy Ernst\u2010Moritz\u2010Arndt\u2010University Greifswald Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Tommerup","sequence":"additional","affiliation":[{"name":"Wilhelm Johannsen Center for Functional Genome Research University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Stephani","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics University Medical Center Schleswig\u2010Holstein Christian\u2010Albrechts University Kiel 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