Exon‐disrupting deletions of NRXN1 in idiopathic generalized epilepsy

• DOI: 10.1111/epi.12078
• Publication Date: 2013-01-07T14:15:08Z
• Authors: Rikke S. Møller; Yvonne G. Weber; Laura L. Klitten; Holger Trucks; Hiltrud Muhle; Wolfram S. Kunz; Heather C. Mefford; Andre Franke; Monika Kautza; Peter Wolf; Dieter Dennig; Stefan Schreiber; Ina‐Maria Rückert; H.‐Erich Wichmann; Jan P. Ernst; Claudia Schurmann; Hans J. Grabe; Niels Tommerup; Ulrich Stephani; Holger Lerche; Helle Hjalgrim; Ingo Helbig; Thomas Sander
• Keywords: Male; Idiopathic generalized epilepsy; Neuronal; Idiopathic Generalized Epilepsy ; 1q21 ; 1 Microdeletion ; Two-hit Hypothesis ; Nrxn1; Neuropsychological Tests; Cell Adhesion Molecules, Neuronal/genetics; 1q21.1 microdeletion; Exons/genetics; Odds Ratio; Nerve Tissue Proteins/genetics; Valproic Acid/therapeutic use; Age of Onset; 0303 health sciences; Triazines; Anticonvulsants/therapeutic use; Electroencephalography; Exons; Middle Aged; Pedigree; 3. Good health; Generalized/drug therapy; Anticonvulsants; Epilepsy, Generalized; Female; Adult ; Age of Onset ; Anticonvulsants ; Case-Control Studies ; Cell Adhesion Molecules, Neuronal ; DNA Copy Number Variations ; Electroencephalography ; Epilepsy, Generalized ; Exons ; Family ; Female ; Fructose ; Gene Deletion ; Genotype ; Humans; Infant ; Male ; Microarray Analysis ; Middle Aged ; Nerve Tissue Proteins ; Neuropsychological Tests ; Odds Ratio ; Pedigree ; Triazines ; Valproic Acid; Adult; Adult, Age of Onset, Anticonvulsants; therapeutic use, Case-Control Studies, Cell Adhesion Molecules; Neuronal; genetics, DNA Copy Number Variations, Electroencephalography, Epilepsy; Generalized; drug therapy/genetics/psychology, Exons; genetics, Family, Female, Fructose; analogs /&/ derivatives/therapeutic use, Gene Deletion, Genotype, Humans, Infant, Male, Microarray Analysis, Middle Aged, Nerve Tissue Proteins; genetics, Neuropsychological Tests, Odds Ratio, Pedigree, Triazines; therapeutic use, Valproic Acid; therapeutic use; DNA Copy Number Variations; Genotype; Cell Adhesion Molecules, Neuronal; Neuronal/genetics; Nerve Tissue Proteins; Fructose; Lamotrigine; NRXN1; 03 medical and health sciences; Topiramate; Epilepsy, Generalized/drug therapy; Humans; Family; Epilepsy; Generalized; Valproic Acid; Calcium-Binding Proteins; Infant; Microarray Analysis; Triazines/therapeutic use; Case-Control Studies; Fructose/analogs & derivatives; Cell Adhesion Molecules; Two-hit hypothesis; Gene Deletion

Summary 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 brain. Recently, deletions and point mutations of neurexin 1 ( NRXN1 ) gene have been associated broad spectrum neuropsychiatric disorders. This study aimed investigate if also increase risk idiopathic generalized epilepsies IGE s). Methods We screened involving 1,569 patients 6,201 controls using high‐density oligonucleotide microarrays. Key Findings identified exon‐disrupting 5 2 control individuals (p = 0.0049; odds ratio OR 9.91, 95% confidence interval CI 1.92–51.12). A familial segregation pattern families was observed, suggesting that heterozygous susceptibility variants. Intriguingly, we second large copy number variant three five index patients, supporting an involvement heterogeneous alleles etiology . Significance conclude represent genetic factor genetically predisposition common syndromes.