伴有发热相关惊厥或癫痫的 SCN9A 新型突变。
Novel mutations in SCN9A occurring with fever-associated seizures or epilepsy.
机构信息
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.
Department of Pediatrics, Guangdong Provincial People's Hospital, Guangzhou 510080, China.
出版信息
Seizure. 2019 Oct;71:214-218. doi: 10.1016/j.seizure.2019.06.005. Epub 2019 Jun 7.
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.
目的
本研究旨在鉴定诊断为发热相关惊厥或癫痫（FASE）的南方汉族个体中的致病基因突变。
方法
从 78 例 FASE 患儿中采集血样和临床数据。所有受试者均采用全外显子组测序进行突变筛查，并采用 Sanger 测序法对突变进行验证。
结果
发现了三个新的 SCN9A 杂合错义突变（I775M、R429C 和 A442T），分别与热性惊厥（FS）、热性惊厥附加症（FS+）和伴热性惊厥附加症的遗传性癫痫（GEFS）有关。R429C 和 A442T 突变位于跨膜拓扑结构域之间的大胞质环中，而 I775M 位于拓扑结构域 DIIS2 中。I775M 和 R429C 突变具有高度进化保守的残基，根据生物信息学工具预测会影响 SCN9A 蛋白功能。这三个突变在 300 名无关对照中未被发现。
结论
SCN9A 基因突变可能与 FASE 相关。
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