Mutations in SCN2A, the gene encoding the brain voltage-gated sodium channel alpha-subunit Na(V)1.2, are associated with inherited epilepsies including benign familial neonatal-infantile seizures (BFNIS).
Mutations in SCN2A, the gene encoding α2 subunit of the neuronal sodium channel, are associated with a variety of epilepsies: benign familial neonatal-infantile seizures (BFNIS); genetic epilepsy with febrile seizures plus (GEFS+); Dravet syndrome (DS); and some intractable childhood epilepsies.
Mutations in the sodium channel genes SCN1A and SCN2A have been identified in monogenic childhood epilepsies, but SCN3A has not previously been investigated as a candidate gene for epilepsy.
Our clinical and experimental data suggest a correlation between age at disease onset, response to sodium channel blockers and the functional properties of mutations in children with SCN2A-related epilepsy.
Our data from the Hong Kong and Malaysia cohorts showed no significant allele, genotype and haplotype association of polymorphisms in the SCN1A, SCN2A, and SCN3A genes with drug responsiveness in epilepsy.
Our findings broaden the clinical spectrum of SCN2A mutations, which resembles clinical phenotypes of SCN1A mutations by manifesting as fever sensitive seizures, and highlights that SCN2A mutations are an important cause of early-onset epileptic encephalopathies with movement disorders.
Overall, results indicate a differential role of genetic polymorphisms of sodium channels SCN1A and SCN2A in epilepsy susceptibility and drug response.
Pathogenic variants in SCN2A are associated with various neurological disorders including epilepsy, autism spectrum disorder and intellectual disability.
Representative of the latter group is Na(v)1.2 (gene name SCN2A): despite its abundance in the brain, Na(v)1.2-related epilepsy is rare and only few studies have been conducted as to the pathophysiological basis of Na(v)1.2 in neuronal hyperexcitability.
Taken together with the previously reported cases, our study suggests that having an extra copy of SCN2A has an effect on epilepsy pathogenesis, causing benign familial infantile seizures which eventually disappear at the age of 1-2 years.
The SCN2A gene encoding α2 subunit of the neuronal sodium channel has been reported to be associated with BFNIS, GFES+, Dravet syndrome and some intractable childhood epilepsies.
The aim of the study was to explore the effect of SCN1A and SCN2A gene polymorphisms on VPA response in the treatment of epilepsy among Chinese patients.
The purpose of this study was to evaluate the frequency of mosaicism detected by next-generation sequencing in genes associated with epilepsy-related neurodevelopmental disorders.MethodsWe conducted a retrospective analysis of 893 probands with epilepsy who had a multigene epilepsy panel or whole-exome sequencing performed in a clinical diagnostic laboratory and were positive for a pathogenic or likely pathogenic variant in one of nine genes (CDKL5, GABRA1, GABRG2, GRIN2B, KCNQ2, MECP2, PCDH19, SCN1A, or SCN2A).
These findings suggest that impaired cortico-striatal excitatory transmission is a plausible mechanism that triggers epilepsy in Stxbp1 and Scn2a haplodeficient mice.