Journal
EPILEPSIA
Volume 54, Issue 2, Pages 256-264Publisher
WILEY
DOI: 10.1111/epi.12078
Keywords
Idiopathic generalized epilepsy; 1q21; 1 microdeletion; Two-hit hypothesis; NRXN1
Categories
Funding
- European Community (FP6 Integrated Project EPICURE) [LSHM-CT-2006-037315]
- German Research Foundation [SA434/4-2]
- German Federal Ministry of Education and Research, National Genome Research Network (NGFNplus: EMINet) [01GS08120, 01GS08123]
- Helmholtz Zentrum Munchen - German Research Center for Environmental Health
- German Federal Ministry of Education and Research
- State of Bavaria
- Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]
- Ministry of Cultural Affairs
- Social Ministry of the Federal State of Mecklenburg-West Pomerania
- Siemens Healthcare, Erlangen, Germany
- Federal State of Mecklenburg-West Pomerania
- Lundbeck Foundation [R67-2010-6206, R151-2013-14290] Funding Source: researchfish
Ask authors/readers for more resources
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) 1.9251.12). 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available