SCN1A mutations were found in 12 of the 71 patients (16.9%; ten with DS, and two with seizures in a Generalized Epilepsy with Febrile Seizures+(GEFS+) context).
We analyzed the occurrence of FS and epilepsy among first- and second-degree relatives (N = 867) of 74 SMEI probands with SCN1A mutations (70 de novo, four inherited) and compared data with age-matched and ethnically matched control families.
We used an ultra-sensitive quantification method, micro-droplet digital PCR (mDDPCR), to detect parental mosaicism of the proband's pathogenic mutation in SCN1A, the causal gene of DS in 112 families.
Approximately 80% of patients with Dravet syndrome have been associated with heterozygous mutations in SCN1A gene encoding voltage-gated sodium channel (VGSC) α(I) subunit, whereas a homozygous mutation (p.Arg125Cys) of SCN1B gene encoding VGSC β(I) subunit was recently described in a patient with Dravet syndrome.
We studied concordant and discordant monozygous twins with de novo mutations in the sodium channel α1 subunit gene (SCN1A) causing Dravet's syndrome, a severe epileptic encephalopathy.
The well established role of de novo mutations of sodium channel SCN1A in Dravet Syndrome supports this view, but the etiology of many cases of epileptic encephalopathy remains unknown.
Complete loss of function in the Na(v) 1.1 channel encoded by the SCN1A gene is associated with severe myoclonic epilepsy in infancy (SMEI), a devastating infantile-onset epilepsy with ataxia, cognitive dysfunction, and febrile and afebrile seizures resistant to current medications.
We expand the phenotypic spectrum of established epilepsy genes by reporting a familial LAMC3 homozygous variant, where the predominant phenotype was epilepsy with myoclonic-atonic seizures, and a pathogenic SCN1A variant in a family where in 5 siblings the phenotype was broadly consistent with Dravet syndrome, a disorder that usually occurs sporadically.
We describe a distinctive speech, language, and oral motor phenotype in children and adults with DS associated with mutations in <i>SCN1A.</i> Recognizing this phenotype will guide therapeutic intervention in patients with DS.
Pathogenic significance of SCN1A splicing variants causing Dravet syndrome: Improving diagnosis with targeted sequencing for variants by in silico analysis.
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.
We investigated how two distinct mutations in SCN1A differentially affect electrophysiological properties of the patient-derived GABAergic neurons and clinical severities in two Dravet syndrome (DS) patients.
Deletions and duplications/amplifications of the α1-sodium channel subunit (SCN1A) gene occur in about 12% of patients with Dravet syndrome (DS) who are otherwise mutation-negative.
Epilepsies associated with SCN1A mutations range in severity from febrile seizures to severe epileptic encephalopathies including Dravet syndrome and severe infantile multifocal epilepsy.
Mutations in the voltage-gated sodium channel (VGSC) gene SCN1A, encoding the Na<sub>v</sub>1.1 channel, are responsible for a number of epilepsy disorders including genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (DS).