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Møller, R.S.* ; Weber, Y.G.* ; Klitten, L.L.* ; Trucks, H.* ; Muhle, H.* ; Kunz, W.S.* ; Mefford, H.C.* ; Franke, A.* ; Kautza, M.* ; Wolf, P.* ; Dennig, D.* ; Schreiber, S.* ; Rückert, I.-M. ; Wichmann, H.-E. ; Ernst, J.P.* ; Schurmann, C.* ; Grabe, H.J.* ; Tommerup, N.* ; Stephani, U.* ; Lerche, H.* ; Hjalgrim, H.* ; Helbig, I.* ; Sander, T.* ; EPICURE Consortium (*)

Exon-disrupting deletions of NRXN1 in idiopathic generalized epilepsy.

Epilepsia 54, 256-264 (2013)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Idiopathic Generalized Epilepsy ; 1q21 ; 1 Microdeletion ; Two-hit Hypothesis ; Nrxn1; Severe Developmental Delay ; Neurodevelopmental Disease ; Increase Risk ; Schizophrenia ; Model ; Microdeletions ; Predispose ; Disorders ; Variants ; Genetics
Language english
Publication Year 2013
HGF-reported in Year 2013
ISSN (print) / ISBN 0013-9580
e-ISSN 1528-1167
Journal Epilepsia
Quellenangaben Volume: 54, Issue: 2, Pages: 256-264 Article Number: , Supplement: ,
Publisher Wiley
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
POF-Topic(s) 30202 - Environmental Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504000-006
G-503900-002
PubMed ID 23294455
DOI 10.1111/epi.12078
WOS ID WOS:000314750200008
Scopus ID 84978024392
Scopus ID 84975095494
Scopus ID 84873411292
Erfassungsdatum 2013-02-22
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