Exon‐disrupting deletions of NRXN1 in idiopathic generalized epilepsy

Medientyp: E-Artikel
Titel: Exon‐disrupting deletions of NRXN1 in idiopathic generalized epilepsy
Beteiligte: Møller, Rikke S.; Weber, Yvonne G.; Klitten, Laura L.; Trucks, Holger; Muhle, Hiltrud; Kunz, Wolfram S.; Mefford, Heather C.; Franke, Andre; Kautza, Monika; Wolf, Peter; Dennig, Dieter; Schreiber, Stefan; Rückert, Ina‐Maria; Wichmann, H.‐Erich; Ernst, Jan P.; Schurmann, Claudia; Grabe, Hans J.; Tommerup, Niels; Stephani, Ulrich; Lerche, Holger; Hjalgrim, Helle; Helbig, Ingo; Sander, Thomas
Erschienen: Wiley, 2013
Erschienen in: Epilepsia
Sprache: Englisch
DOI: 10.1111/epi.12078
ISSN: 0013-9580; 1528-1167
Schlagwörter: Neurology (clinical) ; Neurology
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Beschreibung: <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‐density oligonucleotide microarrays.</jats:p></jats:sec><jats:sec><jats:title>Key Findings</jats:title><jats:p>We identified exon‐disrupting 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 = 0.0049; odds ratio (<jats:styled-content style="fixed-case">OR</jats:styled-content>) 9.91, 95% confidence interval (<jats:styled-content style="fixed-case">CI</jats:styled-content>) 1.92–51.12). 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‐disrupting 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>
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