Rare gene deletions in genetic generalized and Rolandic epilepsies

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http://hdl.handle.net/10138/247098

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EuroEPINOMICS-CoGIE Consortium 2018 , ' Rare gene deletions in genetic generalized and Rolandic epilepsies ' , PLoS One , vol. 13 , no. 8 , 0202022 . https://doi.org/10.1371/journal.pone.0202022

Title: Rare gene deletions in genetic generalized and Rolandic epilepsies
Author: EuroEPINOMICS-CoGIE Consortium
Contributor organization: Institute for Molecular Medicine Finland
University of Helsinki
Medicum
Doctoral Programme Brain & Mind
Research Programme for Molecular Neurology
Department of Medical and Clinical Genetics
Research Programs Unit
Neuroscience Center
Date: 2018-08-27
Language: eng
Number of pages: 23
Belongs to series: PLoS One
ISSN: 1932-6203
DOI: https://doi.org/10.1371/journal.pone.0202022
URI: http://hdl.handle.net/10138/247098
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.
Subject: GENOME-WIDE ASSOCIATION
AUTISM CANDIDATE GENES
COPY NUMBER VARIATION
DE-NOVO MUTATIONS
STRUCTURAL VARIATION
DEVELOPMENTAL DELAY
PARKINSONS-DISEASE
RISK LOCI
VARIANTS
DISORDERS
3111 Biomedicine
3112 Neurosciences
3124 Neurology and psychiatry
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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