More than 100 cases of deletions or duplications of the long arm of chromosome 2 have been reported. Deletion and duplication ranges vary markedly among individual patients. The relationship between range of deletion/duplication and phenotype is not well understood, although seizures and facial dysmorphism are observed commonly in patients with 2q21q31 deletions. Array comparative genomic hybri...

Voltage-gated sodium channels are critical for membrane excitability. Mutations in the genes coding for these proteins cause diseases related to altered excitability of cardiac or skeletal muscle and neurons. Mutations in the central nervous system-specific voltage-gated sodium channel alpha1 subunit gene (SCN1A) lead not only to seizure syndromes but also to familial hemiplegic migraine. The e...

OBJECTIVES Infantile spasms (IS) are severe epileptic encephalopathy during infancy. The SCN1A encodes the α1 subunit of the neuronal voltage-gated sodium channels, and mutations in SCN1A have been frequently detected in idiopathic epilepsy and encephalopathy, which had similar symptoms as IS. Therefore, we investigated the association of SCN1A polymorphism with the IS and the responsiveness to...

Over the past 10 years mutations in voltage-gated sodium channels (Na(v)s) have become closely associated with inheritable forms of epilepsy. One isoform in particular, Na(v)1.1 (gene symbol SCN1A), appears to be a superculprit, registering with more than 330 mutations to date. The associated phenotypes range from benign febrile seizures to extremely serious conditions, such as Dravet's syndrom...

OBJECTIVES To determine the prevalence of Dravet syndrome, an epileptic encephalopathy caused by SCN1A-mutations, often with seizure onset after vaccination, among infants reported with seizures following vaccination. To determine differences in characteristics of reported seizures after vaccination in children with and without SCN1A-related Dravet syndrome. METHODS Data were reviewed of 1,26...

Dravet syndrome (DS) is a developmental and epileptic encephalopathy that results from mutations in the Na v 1.1 sodium channel encoded by SCN1A . Most known DS-causing are coding regions of , but we recently identified several disease-associated intron 20 within or near to cryptic evolutionarily conserved “poison” exon, 20N, whose inclusion predicted lead transcript degradation. However, it no...

Commentary Advances in cellular reprogramming have made it possible to generate virtually any cell type from pluripotent stem cells. Initially, embryonic stem cells were the only source of truly plu-ripotent cells. However, in 2007, it was reported that induced pluripotent stem cells (iPSCs) could be generated from human somatic cells (1, 2). This discovery enabled iPSCs generated from patients...

21 Genetic epilepsy with febrile seizures plus (GEFS+) is an inherited epilepsy 22 which can result from mutations in at least four ion channel subunits. The majority of 23 the known GEFS+ mutations have been identified in SCN1A, the gene encoding 24 Nav1.1 α subunit. Protein kinases as critical modulators of sodium channels have been 25 closely related to the genesis of epilepsy. However, litt...

Mutations in SCN1A, the gene encoding the brain voltage-gated sodium channel alpha1 subunit (NaV1.1), are associated with at least two forms of epilepsy, generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI). We examined the functional properties of four GEFS+ alleles and one SMEI allele using whole-cell patch-clamp analysis of heterologously ex...