title: Novel SCN1A variants in Dravet syndrome and evaluating a wide approach of patient selection.
abstract: Voltage-gated sodium channels are essential for generation and propagation of the action potential mainly in nerve and muscle cells. Causative variants in SCN1A gene which codes the main, pore-forming subunit of the channel expressed in central nervous system are associated predominantly with Dravet syndrome (DS), as well as with generalized epilepsy with febrile seizures plus (GEFS+) making it one of the most significant epilepsy gene. Our goal was to determine whether SCN1A screening is relevant in patients with a broad range of epileptic syndromes. 52 patients diagnosed with DS, generalized epilepsy with GEFS+ or similar types of epileptic syndromes were included. Sequencing of the protein coding parts of the gene complemented with MLPA analysis was carried out. One already described nonsense variant, four novel protein truncating variants and a deletion encompassing the whole SCN1A gene were revealed, all in heterozygous state. All identified variants were found in DS patients with 85.7% sensitivity, thus supporting the role of profound SCN1A gene variants in etiology of DS phenotype. No causative variants were identified in any of non-DS epileptic patients in our cohort, suggesting a minor, but not irrelevant role for SCN1A in patients with other types of childhood epilepsy.
authors.affiliation: Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, Mlynska dolina Bratislava, 842 15 Slovak Republic. milan.surovy015@gmail.com.
authors.forename: Milan
authors.initials: M
authors.lastname: Surovy
authors.forename: Andrea
authors.initials: A
authors.lastname: Soltysova
authors.forename: Miriam
authors.initials: M
authors.lastname: Kolnikova
authors.forename: Pavol
authors.initials: P
authors.lastname: Sykora
authors.forename: Denisa
authors.initials: D
authors.lastname: Ilencikova
authors.forename: Andrej
authors.initials: A
authors.lastname: Ficek
authors.forename: Jan
authors.initials: J
authors.lastname: Radvanszky
authors.forename: Ludevit
authors.initials: L
authors.lastname: Kadasi
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004831:Epilepsies, Myoclonic / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D018579:Patient Selection; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D011379:Prognosis; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D018154:Slovakia / Q000453:epidemiology; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human