Ayberk Türkyılmaz1, Emine Tekin2, Oğuzhan Yaralı3, Alper Han Çebi1. 1. Department of Medical Genetics, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey. 2. Department of Pediatric Neurology, Faculty of Medicine, Giresun University, Giresun, Turkey. 3. Clinic of Medical Genetics, Erzurum Training and Research Hospital, Erzurum, Turkey.
Abstract
Introduction: The α subunit of voltage-gated sodium channels in mammals is encoded by 9 different genes, and variations in the SCN1A, SCN2A, SCN3A, and SCN8A genes highly expressed in the CNS have been associated with epilepsy phenotypes. This study aimed at investigating the frequency of SCN1A gene variations in Dravet syndrome (DS) and GEFS+ spectrum phenotype cases and discussing the molecular results in the context of genotype-phenotype correlation. Methods: Fifteen patients diagnosed with DS and 54 patients meeting the GEFS+ spectrum criteria were included in this study. All patients were evaluated by next-generation sequencing and multiplex ligation-dependent probe amplification using an SCN1A gene commercial kit. Results: A total of 17 different variants were detected in 18 index cases (26%), of which 7 were novel variations (p.M1R, p.M147T, p.I767L, p.N1391Ifs*5, p.R1886G, p.E1915G, p.R1933Q). Of the 18 cases with variation in the SCN1A gene, 12 had DS and 6 had GEFS+ phenotype. The variations were de novo in all DS cases and in 1 case with a GEFS+ phenotype; in 5 GEFS+ cases, the variant was inherited from the affected parent. Discussion: This study contributes to the variation spectrum in cases with DS and GEFS+ phenotype with the novel variants detected. SCN1A genetic analysis can help in determining whether antiseizure medication should be selected or avoided in cases with variations. The elucidation of the molecular etiology makes it possible to provide the family with effective genetic counseling for future pregnancies.
Introduction: The α subunit of voltage-gated sodium channels in mammals is encoded by 9 different genes, and variations in the SCN1A, SCN2A, SCN3A, and SCN8A genes highly expressed in the CNS have been associated with epilepsy phenotypes. This study aimed at investigating the frequency of SCN1A gene variations in Dravet syndrome (DS) and GEFS+ spectrum phenotype cases and discussing the molecular results in the context of genotype-phenotype correlation. Methods: Fifteen patients diagnosed with DS and 54 patients meeting the GEFS+ spectrum criteria were included in this study. All patients were evaluated by next-generation sequencing and multiplex ligation-dependent probe amplification using an SCN1A gene commercial kit. Results: A total of 17 different variants were detected in 18 index cases (26%), of which 7 were novel variations (p.M1R, p.M147T, p.I767L, p.N1391Ifs*5, p.R1886G, p.E1915G, p.R1933Q). Of the 18 cases with variation in the SCN1A gene, 12 had DS and 6 had GEFS+ phenotype. The variations were de novo in all DS cases and in 1 case with a GEFS+ phenotype; in 5 GEFS+ cases, the variant was inherited from the affected parent. Discussion: This study contributes to the variation spectrum in cases with DS and GEFS+ phenotype with the novel variants detected. SCN1A genetic analysis can help in determining whether antiseizure medication should be selected or avoided in cases with variations. The elucidation of the molecular etiology makes it possible to provide the family with effective genetic counseling for future pregnancies.
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