Prediction of molecular phenotypes for novel SCN1A variants from a Turkish genetic epilepsy syndromes cohort and report of two new patients with recessive Dravet syndrome.

Autor: Teralı K; Department of Medical Biochemistry, Faculty of Medicine, Cyprus International University, Nicosia, Cyprus., Türkyılmaz A; Department of Medical Genetics, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey., Sağer SG; Department of Pediatric Neurology, Kartal Dr. Lütfi Kırdar City Hospital, İstanbul, Turkey., Çebi AH; Department of Medical Genetics, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey.
Jazyk: angličtina
Zdroj: Clinical and translational science [Clin Transl Sci] 2024 Jan; Vol. 17 (1), pp. e13679. Date of Electronic Publication: 2023 Dec 06.
DOI: 10.1111/cts.13679
Abstrakt: Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+) are both epilepsy syndromes that can be attributed to deleterious mutations occurring in SCN1A, the gene encoding the pore-forming α-subunit of the Na V 1.1 voltage-gated sodium channel predominantly expressed in the central nervous system. In this research endeavor, our goal is to expand our prior cohort of Turkish patients affected by SCN1A-positive genetic epilepsy disorders. This will be accomplished by incorporating two recently discovered and infrequent index cases who possess a novel biallelic (homozygous) SCN1A missense variant, namely E158G, associated with Dravet syndrome. Furthermore, our intention is to use computational techniques to predict the molecular phenotypes of each distinct SCN1A variant that has been detected to date within our center. The correlation between genotype and phenotype in Dravet syndrome/GEFS+ is intricate and necessitates meticulous clinical investigation as well as advanced scientific exploration. Broadened mechanistic and structural insights into Na V 1.1 dysfunction offer significant promise in facilitating the development of targeted and effective therapies, which will ultimately enhance clinical outcomes in the treatment of epilepsy.
(© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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