Exome data of developmental and epileptic encephalopathy patients reveals de novo and inherited pathologic variants in epilepsy-associated genes

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dc.authoridYalcin Capan, Ozlem/0000-0002-7511-3355
dc.contributor.authorCapan, Ozlem Yalcin
dc.contributor.authorYapici, Zuhal
dc.contributor.authorOzbil, Mehmet
dc.contributor.authorCaglayan, Hande S.
dc.date.accessioned2024-10-29T17:58:29Z
dc.date.available2024-10-29T17:58:29Z
dc.date.issued2024
dc.departmentTekirdağ Namık Kemal Üniversitesi
dc.description.abstractPurpose: In Developmental and Epileptic Encephalopathies (DEEs), identifying the precise genetic factors guides the clinicians to apply the most appropriate treatment for the patient. Due to high locus heterogeneity, WES analysis is a promising approach for the genetic diagnosis of DEE. Therefore, the aim of the present study is to evaluate the utility of WES in the diagnosis and treatment of DEE patients. Methods: The exome data of 29 DEE patients were filtrated for destructive and missense mutations in 1896 epilepsy-related genes to detect the causative variants and examine the genotype-phenotype correlations. We performed Sanger sequencing with the available DNA samples to follow the co-segregation of the variants with the disease phenotype in the families. Also, the structural effects of p.Asn1053Ser, p.Pro120Ser and p. Glu1868Gly mutations on KCNMA1, NPC2, and SCN2A proteins, respectively, were evaluated by molecular dynamics (MD) and molecular docking simulations. Results: Out of 29, nine patients (31%) harbor pathological (P) or likely pathological (LP) mutations in SCN2A, KCNQ2, ATP1A2, KCNMA1, and MECP2 genes, and three patients have VUS variants (10%) in SCN1A and SCN2A genes. Sanger sequencing results indicated that three of the patients have de novo mutations while eight of them carry paternally and/or maternally inherited causative variants. MD and molecular docking simulations supported the destructive effects of the mutations on KCNMA1, NPC2, and SCN2A protein structures. Conclusion: Herein we demonstrated the effectiveness of WES for DEE with high locus heterogeneity. Identification of the genetic etiology guided the clinicians to adjust the proper treatment for the patients.
dc.description.sponsorshipBogazici University Scientific Research Projects (BAP) [17B01P3-12776]; Istanbul Arel University Scientific Research Projects [2019-ST02]
dc.description.sponsorshipThe research project was partially funded by Bogazici University Scientific Research Projects (BAP no: 17B01P3-12776) and Istanbul Arel University Scientific Research Projects (BAP no: 2019-ST02) . We thank Kamer Nisa Baz for her contribution to computational data production and Asl & imath; Guendogdu for her contribution to DNA extraction and organization of patient data.
dc.identifier.doi10.1016/j.seizure.2023.06.009
dc.identifier.endpage64
dc.identifier.issn1059-1311
dc.identifier.issn1532-2688
dc.identifier.pmid37353388
dc.identifier.scopus2-s2.0-85162856548
dc.identifier.scopusqualityQ2
dc.identifier.startpage51
dc.identifier.urihttps://doi.org/10.1016/j.seizure.2023.06.009
dc.identifier.urihttps://hdl.handle.net/20.500.11776/14346
dc.identifier.volume116
dc.identifier.wosWOS:001225708500001
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherW B Saunders Co Ltd
dc.relation.ispartofSeizure-European Journal of Epilepsy
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectDevelopmental and epileptic encephalopathies
dc.subjectWhole exome sequencing
dc.subjectMolecular dynamics (MD) simulations
dc.subjectMolecular docking
dc.subjectSCN1A
dc.subjectSCN2A
dc.subjectKCNQ2
dc.subjectKCNMA1
dc.subjectMECP2
dc.subjectNPC2
dc.subjectCLN6
dc.titleExome data of developmental and epileptic encephalopathy patients reveals de novo and inherited pathologic variants in epilepsy-associated genes
dc.typeArticle

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