Sodium voltage-gated channel alpha subunit 9 mutation in epilepsy

Abstract

In humans, gene mutations in volt- age-gated sodium channels can cause a range

of epileptic symptoms, including genetic (gen- eralized) epilepsy with febrile seizures plus

(GEFS+) and Dravet syndrome (DS). The SCN9A

is a member of the SCN9 gene family that en- codes sodium transporter proteins. In the cur- rent case report, we delineate a 12-year-old pa- tient who was referred to a pediatric neurology

clinic for infantile-onset generalized epileptic seizures and progressive neurodevelopmental delay. Novel heterozygous mutations c.4702A>C (p.Asn1568His) in the SCN9A gene, and c.65G>A (p.Arg22Gln) in the MLC1 gene were detected

using targeted next-generation gene sequenc- ing. The replacement of Histidine (His) with As- paragine (Asn) at position 1568 in the topologi- cal domain of SCN9A channel protein provides

new insights into the impaired excitation and inactivation patterns of sodium channels. The case report adds this new patient with genetic

link of SCN9A variants with progressive myoc- lonic epilepsy and cognitive difficulties.