Molecular genetic basis of childhood epilepsy in Serbia: utility of clinical and whole exome sequencing
Аутори
Anđelković, MarinaKlaassen, Kristel
Skakić, Anita
Marjanović, Irena
Kravljanac, Ružica
Đorđević, Maja
Vučetić Tadić, Biljana
Kecman Božica
Pavlović, Sonja
Stojiljković, Maja
Остала ауторства
Morić, IvanaĐorđević, Valentina
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Кључне речи:
childhood epilepsy / monogenic disease / CES / WES / novel genetic variantsИзвор:
5th Belgrade Bioinformatics Conference, 2024, 113-113Издавач:
- Belgrade : Institute of molecular genetics and genetic engineering
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200042 (Универзитет у Београду, Институт за молекуларну генетику и генетичко инжењерство) (RS-MESTD-inst-2020-200042)
Напомена:
- Book of abstracts: 5th Belgrade Bioinformatics Conference, Serbia, Belgrade,17-20 june 2024.
Колекције
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Anđelković, Marina AU - Klaassen, Kristel AU - Skakić, Anita AU - Marjanović, Irena AU - Kravljanac, Ružica AU - Đorđević, Maja AU - Vučetić Tadić, Biljana AU - Kecman Božica AU - Pavlović, Sonja AU - Stojiljković, Maja PY - 2024 UR - www.belbi.bg.ac.rs UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2471 AB - 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. PB - Belgrade : Institute of molecular genetics and genetic engineering C3 - 5th Belgrade Bioinformatics Conference T1 - Molecular genetic basis of childhood epilepsy in Serbia: utility of clinical and whole exome sequencing EP - 113 SP - 113 UR - https://hdl.handle.net/21.15107/rcub_imagine_2471 ER -
@conference{ author = "Anđelković, Marina and Klaassen, Kristel and Skakić, Anita and Marjanović, Irena and Kravljanac, Ružica and Đorđević, Maja and Vučetić Tadić, Biljana and Kecman Božica and Pavlović, Sonja and Stojiljković, Maja", year = "2024", 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.", publisher = "Belgrade : Institute of molecular genetics and genetic engineering", journal = "5th Belgrade Bioinformatics Conference", title = "Molecular genetic basis of childhood epilepsy in Serbia: utility of clinical and whole exome sequencing", pages = "113-113", url = "https://hdl.handle.net/21.15107/rcub_imagine_2471" }
Anđelković, M., Klaassen, K., Skakić, A., Marjanović, I., Kravljanac, R., Đorđević, M., Vučetić Tadić, B., Kecman Božica, Pavlović, S.,& Stojiljković, M.. (2024). Molecular genetic basis of childhood epilepsy in Serbia: utility of clinical and whole exome sequencing. in 5th Belgrade Bioinformatics Conference Belgrade : Institute of molecular genetics and genetic engineering., 113-113. https://hdl.handle.net/21.15107/rcub_imagine_2471
Anđelković M, Klaassen K, Skakić A, Marjanović I, Kravljanac R, Đorđević M, Vučetić Tadić B, Kecman Božica, Pavlović S, Stojiljković M. Molecular genetic basis of childhood epilepsy in Serbia: utility of clinical and whole exome sequencing. in 5th Belgrade Bioinformatics Conference. 2024;:113-113. https://hdl.handle.net/21.15107/rcub_imagine_2471 .
Anđelković, Marina, Klaassen, Kristel, Skakić, Anita, Marjanović, Irena, Kravljanac, Ružica, Đorđević, Maja, Vučetić Tadić, Biljana, Kecman Božica, Pavlović, Sonja, Stojiljković, Maja, "Molecular genetic basis of childhood epilepsy in Serbia: utility of clinical and whole exome sequencing" in 5th Belgrade Bioinformatics Conference (2024):113-113, https://hdl.handle.net/21.15107/rcub_imagine_2471 .