Open AccessNovel SCN1A variants in Dravet syndrome and evaluating a wide approach of patient selection
Author(s) -
Milan Surovy,
Andrea Šoltýsová,
Miriam Kolníková,
Pavol Sýkora,
Denisa Ilenčíková,
Andrej Ficek,
Ján Radvánszky,
Ľudevít Kádaši
Publication year - 2016
Publication title -
general physiology and biophysics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.376
H-Index - 39
eISSN - 1338-4325
pISSN - 0231-5882
DOI - 10.4149/gpb_2016002
Subject(s) - dravet syndrome , epilepsy , epilepsy syndromes , scn3a , multiplex ligation dependent probe amplification , gene , etiology , medicine , sodium channel , genetics , phenotype , bioinformatics , biology , g alpha subunit , neuroscience , protein subunit , exon , chemistry , organic chemistry , sodium
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.