Journalartikel
Autorenliste: Jabbari, Kamel; Bobbili, Dheeraj R.; Lal, Dennis; Reinthaler, Eva M.; Schubert, Julian; Wolking, Stefan; Sinha, Vishal; Motameny, Susanne; Thiele, Holger; Kawalia, Amit; Altmueller, Janine; Toliat, Mohammad Reza; Kraaij, Robert; van Rooij, Jeroen; Uitterlinden, Andre G.; Ikram, M. Arfan; Zara, Federico; Lehesjoki, Anna-Elina; Krause, Roland; Zimprich, Fritz; Sander, Thomas; Neubauer, Bernd A.; May, Patrick; Lerche, Holger; Nuernberg, Peter
Jahr der Veröffentlichung: 2018
Zeitschrift: PLoS ONE
Bandnummer: 13
Heftnummer: 8
ISSN: 1932-6203
Open Access Status: Gold
DOI Link: https://doi.org/10.1371/journal.pone.0202022
Verlag: Public Library of Science
Abstract:
Genetic Generalized Epilepsy (GGE) and benign epilepsy with centro-temporal spikes or Rolandic Epilepsy (RE) are common forms of genetic epilepsies. Rare copy number variants have been recognized as important risk factors in brain disorders. We performed a systematic survey of rare deletions affecting protein-coding genes derived from exome data of patients with common forms of genetic epilepsies. We analysed exomes from 390 European patients (196 GGE and 194 RE) and 572 population controls to identify low-frequency genic deletions. We found that 75 (32 GGE and 43 RE) patients out of 390, i.e. similar to 19%, carried rare genic deletions. In particular, large deletions (>400 kb) represent a higher burden in both GGE and RE syndromes as compared to controls. The detected low-frequency deletions (1) share genes with brain-expressed exons that are under negative selection, (2) overlap with known autism and epilepsy-associated candidate genes, (3) are enriched for CNV intolerant genes recorded by the Exome Aggregation Consortium (ExAC) and (4) coincide with likely disruptive de novo mutations from the NPdenovo database. Employing several knowledge databases, we discuss the most prominent epilepsy candidate genes and their protein-protein networks for GGE and RE.
Zitierstile
Harvard-Zitierstil: Jabbari, K., Bobbili, D., Lal, D., Reinthaler, E., Schubert, J., Wolking, S., et al. (2018) Rare gene deletions in genetic generalized and Rolandic epilepsies, PLoS ONE, 13(8), Article e0202022. https://doi.org/10.1371/journal.pone.0202022
APA-Zitierstil: Jabbari, K., Bobbili, D., Lal, D., Reinthaler, E., Schubert, J., Wolking, S., Sinha, V., Motameny, S., Thiele, H., Kawalia, A., Altmueller, J., Toliat, M., Kraaij, R., van Rooij, J., Uitterlinden, A., Ikram, M., Zara, F., Lehesjoki, A., Krause, R., ...Nuernberg, P. (2018). Rare gene deletions in genetic generalized and Rolandic epilepsies. PLoS ONE. 13(8), Article e0202022. https://doi.org/10.1371/journal.pone.0202022
Schlagwörter
ATAXIA; CANDIDATE; DE-NOVO MUTATIONS; GENOME-WIDE ASSOCIATION; STRUCTURAL VARIATION; VARIANTS
