Novel mutations in SCN9A occurring with fever-associated seizures or epilepsy

Abstract

Purpose: This study aimed to identify disease-causing gene mutations in individuals belonging to the Southern Chinese Han population diagnosed with fever-associated seizures or epilepsy (FASE).

Methods: Blood samples and clinical data were collected from 78 children with FASE. All subjects were screened for mutations using whole-exome sequencing, and mutations were validated using the Sanger sequencing method.

Results: Three novelSCN9A heterozygous missense mutations (I775M, R429C and A442T) were noted, which are associated with febrile seizures (FS), febrile seizures plus (FS⁺) and genetic epilepsy with febrile seizures plus (GEFS⁺), respectively. The R429C and A442T mutations are located in the large cytoplasmic loop between transmembrane topological domains, whereas I775M is located in the topological domain DIIS2. The I775M and R429C mutations have highly evolutionarily conserved residues and are predicted to affect the SCN9A protein function according to bioinformatics tools. These three mutations were not identified in 300 unrelated control subjects.

Conclusions: Mutations in theSCN9A gene may be linked with FASE.

Keywords: Clinical phenotype; Fever-associated seizures or epilepsy (FASE); Genotype; SCN9A.