title: The SCN1A gene variants and epileptic encephalopathies.
abstract: The voltage-gated sodium channels are fundamental units that evoke the action potential in excitable cells such as neurons. These channels are integral membrane proteins typically consisting of one α-subunit, which forms the larger central pore of the channel, and two smaller auxiliary β-subunits, which modulate the channel functions. Genetic alterations in the SCN1A gene coding for the α-subunit of the neuronal voltage-gated sodium ion channel, type 1 (NaV 1.1), is associated with a spectrum of seizure-related disorders in human, ranging from a relatively milder form of febrile seizures to a more severe epileptic condition known as the Dravet syndrome. Among the epilepsy genes, the SCN1A gene perhaps known to have the largest number of disease-associated alleles. Here we present a meta-analysis on the SCN1A gene variants and provide comprehensive information on epilepsy-associated gene variants, their frequency, the predicted effect on the protein, the ethnicity of the affected along with the inheritance pattern and the associated epileptic phenotype. We also summarize our current understanding on the pathophysiology of the SCN1A gene defects, disease mechanism, genetic modifiers and their clinical and diagnostic relevance.
authors.affiliation: 1] Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, India [2] Department of Biochemistry, G.R.Medical College, Gwalior, India.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Parihar
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Ganesh
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004831:Epilepsies, Myoclonic / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D056726:Genetic Association Studies; D014644:Genetic Variation / Q000502:physiology; D006801:Humans; D051379:Mice; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human