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Molecular genetic basis of childhood epilepsy in Serbia: utility of clinical and whole exome sequencing
dc.contributor | Morić, Ivana | |
dc.contributor | Đorđević, Valentina | |
dc.creator | Anđelković, Marina | |
dc.creator | Klaassen, Kristel | |
dc.creator | Skakić, Anita | |
dc.creator | Marjanović, Irena | |
dc.creator | Kravljanac, Ružica | |
dc.creator | Đorđević, Maja | |
dc.creator | Vučetić Tadić, Biljana | |
dc.creator | Kecman Božica | |
dc.creator | Pavlović, Sonja | |
dc.creator | Stojiljković, Maja | |
dc.date.accessioned | 2024-07-24T22:04:40Z | |
dc.date.available | 2024-07-24T22:04:40Z | |
dc.date.issued | 2024 | |
dc.identifier.isbn | 978-86-82679-16-5 | |
dc.identifier.uri | www.belbi.bg.ac.rs | |
dc.identifier.uri | https://imagine.imgge.bg.ac.rs/handle/123456789/2471 | |
dc.description.abstract | Childhood epilepsies are caused by heterogeneous underlying disorders where approximately 40% of the origins of epilepsy can be attributed to genetic factors. The application of next-generation sequencing (NGS) has revolutionized molecular diagnostics and has enabled identification of disease-causing genes and variants in epilepsies. In our study, 55 children with epilepsy of unknown etiology were analyzed combining clinical-exome (CES) and whole-exome sequencing (WES). Novel variants were characterized using various in silico algorithms for pathogenicity and structure prediction. Molecular genetic cause of epilepsy was identified in 28 patients and the overall diagnostic success rate was 50.9%. We identified variants in 22 different genes associated with epilepsy that correlate well with the described phenotype. SCN1A gene variants were found in 5 unrelated patients, while ALDH7A1 and KCNQ2 gene variants were found twice. In the other 19 genes, variants were found only in a single patient. This includes genes: ASH1L, CSNK2B RHOBTB2 and SLC13A5, which have only recently been associated with epilepsy. Almost half of diagnosed patients (46.4%) carried novel variants. Interestingly, identification of variants in ALDH7A1, KCNQ2, PNPO, SCN1A and SCN2A gene directed therapy decision of 11 children from our study, including four children who all carry novel SCN1A genetic variants. Our study emphasizes the importance of NGS in diagnosing childhood epilepsy. With an increasing number of genes associated with epilepsy, comprehensive analysis using CES and WES is crucial for high diagnostic success. Given the expansion of molecular-based approaches, each newly identified genetic variant could become a potential therapeutic target. | sr |
dc.language.iso | en | sr |
dc.publisher | Belgrade : Institute of molecular genetics and genetic engineering | sr |
dc.relation | info:eu-repo/grantAgreement/MESTD/inst-2020/200042/RS// | sr |
dc.rights | openAccess | sr |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | 5th Belgrade Bioinformatics Conference | sr |
dc.subject | childhood epilepsy | sr |
dc.subject | monogenic disease | sr |
dc.subject | CES | sr |
dc.subject | WES | sr |
dc.subject | novel genetic variants | sr |
dc.title | Molecular genetic basis of childhood epilepsy in Serbia: utility of clinical and whole exome sequencing | sr |
dc.type | conferenceObject | sr |
dc.rights.license | BY-NC-ND | sr |
dc.rights.holder | © 2024 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade | sr |
dc.citation.epage | 113 | |
dc.citation.spage | 113 | |
dc.description.other | Book of abstracts: 5th Belgrade Bioinformatics Conference, Serbia, Belgrade,17-20 june 2024. | sr |
dc.identifier.fulltext | https://imagine.imgge.bg.ac.rs/bitstream/id/845722/BelBi2024-Book-of-Abstracts_1-16,129,141-142.pdf | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_imagine_2471 | |
dc.type.version | publishedVersion | sr |