Jian Ding1, Jing-Wen Zhang2, Yu-Xiong Guo2, Yu-Xin Zhang2, Zhi-Hong Chen2, Qiong-Xiang Zhai3. 1. The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China; Department of Pediatrics, Guangdong Provincial People's Hospital, Guangzhou 510080, China; Department of Pediatrics, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan, 523059, China. 2. Department of Pediatrics, Guangdong Provincial People's Hospital, Guangzhou 510080, China. 3. The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China; Department of Pediatrics, Guangdong Provincial People's Hospital, Guangzhou 510080, China. Electronic address: zhaiqiongxiang@sina.com.
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.
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.