CHARACTERIZATION OF 16 NOVEL GENETIC VARIANTS IN GENES RELATED TO CHILDHOOD EPILEPSIES
Аутори
Anđelković, MarinaKlaassen, Kristel
Skakić, Anita
Marjanović, Irena
Kravljana, Ruzica
Đorđević, Maja
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Background: Childhood epilepsies are
caused by heterogeneous underlying disorders where
approximately 40% can be attributed to genetic
factors. Application of next-generation sequencing
(NGS) has revolutionized diagnostics and therefore
has enabled the identification of disease-causing
genes and variants in childhood epilepsies.
Materials and Methods: Patients who presented
with epilepsy of unknown etiology in childhood,
with suspicion of a genetic cause were included
in this study. In total, 55 patients from unrelated
non-consanguineous families were included and analyzed
by NGS either using clinical-exome sequencing
(MiSeq, Illumina) or whole-exome sequencing
(DNBSEQ-G400, MGI). Variants were prioritized
using Variant Interpreter and VarSome and classified
according to the ACMG recommendations.
Results: Using CES we analyzed 38 patients,
and for 22 of them a diagnosis was established.
Using WES we analyzed 17 patients with childhood epilepsy, which led to the ident...ification of
disease-causing genes in 11 patients. The diagnostic
success rate for CES was 55.3% (21/38) and the
diagnostic rate for WES was 64.7% (11/17), with
the overall diagnostic rate being 58.2% (32/55). For
these patients, we detected pathogenic, likely pathogenic
variants or VUS in 24 epilepsy genes that
correlate well to the observed phenotype. Sixteen
novel genetic variants were identified and characterized
using various in silico algorithms.
Conclusion: This is the first study reporting
the molecular-genetic basis of childhood epilepsy
in Serbia. The prompt establishment of a specific
diagnosis is essential in order to make available the
prognosis, optimize therapy, and enable counseling
on recurrence risk in future pregnancies.
Кључне речи:
childhood epilepsy / CES / WES / novel variants / rare diseasesИзвор:
International Journal of Medical Genetics, 2023, 26, Supplement, 114-114Издавач:
- Macedonian Academy of Sciences and Arts
Напомена:
- ABSTRACT BOOK: “Genetic Diseases from Diagnostics to Prevention and Therapy” October 05-14th Balkan Congress of Human Genetics & 9th Rare Disease SEE Meeting 2023; Skopje, October 05-07, 2023
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Anđelković, Marina AU - Klaassen, Kristel AU - Skakić, Anita AU - Marjanović, Irena AU - Kravljana, Ruzica AU - Đorđević, Maja PY - 2023 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2179 AB - Background: Childhood epilepsies are caused by heterogeneous underlying disorders where approximately 40% can be attributed to genetic factors. Application of next-generation sequencing (NGS) has revolutionized diagnostics and therefore has enabled the identification of disease-causing genes and variants in childhood epilepsies. Materials and Methods: Patients who presented with epilepsy of unknown etiology in childhood, with suspicion of a genetic cause were included in this study. In total, 55 patients from unrelated non-consanguineous families were included and analyzed by NGS either using clinical-exome sequencing (MiSeq, Illumina) or whole-exome sequencing (DNBSEQ-G400, MGI). Variants were prioritized using Variant Interpreter and VarSome and classified according to the ACMG recommendations. Results: Using CES we analyzed 38 patients, and for 22 of them a diagnosis was established. Using WES we analyzed 17 patients with childhood epilepsy, which led to the identification of disease-causing genes in 11 patients. The diagnostic success rate for CES was 55.3% (21/38) and the diagnostic rate for WES was 64.7% (11/17), with the overall diagnostic rate being 58.2% (32/55). For these patients, we detected pathogenic, likely pathogenic variants or VUS in 24 epilepsy genes that correlate well to the observed phenotype. Sixteen novel genetic variants were identified and characterized using various in silico algorithms. Conclusion: This is the first study reporting the molecular-genetic basis of childhood epilepsy in Serbia. The prompt establishment of a specific diagnosis is essential in order to make available the prognosis, optimize therapy, and enable counseling on recurrence risk in future pregnancies. PB - Macedonian Academy of Sciences and Arts C3 - International Journal of Medical Genetics T1 - CHARACTERIZATION OF 16 NOVEL GENETIC VARIANTS IN GENES RELATED TO CHILDHOOD EPILEPSIES EP - 114 IS - Supplement SP - 114 VL - 26 UR - https://hdl.handle.net/21.15107/rcub_imagine_2179 ER -
@conference{ author = "Anđelković, Marina and Klaassen, Kristel and Skakić, Anita and Marjanović, Irena and Kravljana, Ruzica and Đorđević, Maja", year = "2023", abstract = "Background: Childhood epilepsies are caused by heterogeneous underlying disorders where approximately 40% can be attributed to genetic factors. Application of next-generation sequencing (NGS) has revolutionized diagnostics and therefore has enabled the identification of disease-causing genes and variants in childhood epilepsies. Materials and Methods: Patients who presented with epilepsy of unknown etiology in childhood, with suspicion of a genetic cause were included in this study. In total, 55 patients from unrelated non-consanguineous families were included and analyzed by NGS either using clinical-exome sequencing (MiSeq, Illumina) or whole-exome sequencing (DNBSEQ-G400, MGI). Variants were prioritized using Variant Interpreter and VarSome and classified according to the ACMG recommendations. Results: Using CES we analyzed 38 patients, and for 22 of them a diagnosis was established. Using WES we analyzed 17 patients with childhood epilepsy, which led to the identification of disease-causing genes in 11 patients. The diagnostic success rate for CES was 55.3% (21/38) and the diagnostic rate for WES was 64.7% (11/17), with the overall diagnostic rate being 58.2% (32/55). For these patients, we detected pathogenic, likely pathogenic variants or VUS in 24 epilepsy genes that correlate well to the observed phenotype. Sixteen novel genetic variants were identified and characterized using various in silico algorithms. Conclusion: This is the first study reporting the molecular-genetic basis of childhood epilepsy in Serbia. The prompt establishment of a specific diagnosis is essential in order to make available the prognosis, optimize therapy, and enable counseling on recurrence risk in future pregnancies.", publisher = "Macedonian Academy of Sciences and Arts", journal = "International Journal of Medical Genetics", title = "CHARACTERIZATION OF 16 NOVEL GENETIC VARIANTS IN GENES RELATED TO CHILDHOOD EPILEPSIES", pages = "114-114", number = "Supplement", volume = "26", url = "https://hdl.handle.net/21.15107/rcub_imagine_2179" }
Anđelković, M., Klaassen, K., Skakić, A., Marjanović, I., Kravljana, R.,& Đorđević, M.. (2023). CHARACTERIZATION OF 16 NOVEL GENETIC VARIANTS IN GENES RELATED TO CHILDHOOD EPILEPSIES. in International Journal of Medical Genetics Macedonian Academy of Sciences and Arts., 26(Supplement), 114-114. https://hdl.handle.net/21.15107/rcub_imagine_2179
Anđelković M, Klaassen K, Skakić A, Marjanović I, Kravljana R, Đorđević M. CHARACTERIZATION OF 16 NOVEL GENETIC VARIANTS IN GENES RELATED TO CHILDHOOD EPILEPSIES. in International Journal of Medical Genetics. 2023;26(Supplement):114-114. https://hdl.handle.net/21.15107/rcub_imagine_2179 .
Anđelković, Marina, Klaassen, Kristel, Skakić, Anita, Marjanović, Irena, Kravljana, Ruzica, Đorđević, Maja, "CHARACTERIZATION OF 16 NOVEL GENETIC VARIANTS IN GENES RELATED TO CHILDHOOD EPILEPSIES" in International Journal of Medical Genetics, 26, no. Supplement (2023):114-114, https://hdl.handle.net/21.15107/rcub_imagine_2179 .