These authors contributed equally to this study.
Full-Length Original Research
Exon-disrupting deletions of NRXN1 in idiopathic generalized epilepsy
Article first published online: 7 JAN 2013
Wiley Periodicals, Inc. © 2012 International League Against Epilepsy
Volume 54, Issue 2, pages 256–264, February 2013
How to Cite
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. and EPICURE Consortium (2013), Exon-disrupting deletions of NRXN1 in idiopathic generalized epilepsy. Epilepsia, 54: 256–264. doi: 10.1111/epi.12078
- Issue published online: 5 FEB 2013
- Article first published online: 7 JAN 2013
- Manuscript Accepted: 14 NOV 2012
- European Community. Grant Number: LSHM-CT-2006-037315
- German Research Foundation. Grant Number: SA434/4-2
- German Federal Ministry of Education and Research
- National Genome Research Network. Grant Numbers: 01GS08120, 01GS08123
- Helmholtz Zentrum München – German Research Center for Environmental Health
- State of Bavaria. Grant Numbers: 01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012
Vol. 54, Issue 12, 2232, Article first published online: 4 DEC 2013
- Idiopathic generalized epilepsy;
- 1q21.1 microdeletion;
- Two-hit hypothesis;
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).
We screened for deletions involving the NRXN1 gene in 1,569 patients with IGE and 6,201 controls using high-density oligonucleotide microarrays.
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.
We conclude that exon-disrupting deletions of NRXN1 represent a genetic risk factor in the genetically complex predisposition of common IGE syndromes.