SCN9A基因突变癫痫患儿基因型与表型分析

Genotype and Phenotype Study of Children with Epilepsy and SCN9A Gene Mutation

目的:探讨SCN9A基因突变癫痫患儿基因型与表型的特点。方法:收集2016年6月-2018年5月广东省人民医院儿科就诊的癫痫患儿,采用全外显子组测序筛选突变,并采用Sanger测序方法验证突变。结果:共发现6例患儿存在SCN9A基因突变,男女各3例,检测到6个不同位点的突变,均为杂合错义突变,且为遗传性突变,导致了氨基酸改变,其中5例突变位点分布在高度保守的区域。临床发作类型:4例(66.7%)全面性强直-阵挛发作,1例(16.7%)局灶性发作,1例(16.7%)失张力发作;3例(50.0%)患儿发作有热敏感特点。有多种临床表型,热性惊厥附加症1例,遗传性癫痫伴热性惊厥附加症1例,Dravet综合征1例,额叶癫痫1例,不明分类的癫痫2例。结论:SCN9A基因突变以杂合的错义突变为主,大部分突变定位在高度保守的区域,发作类型以全面性发作为主,多数与热相关,临床表型谱广。

Objective:To explore the characteristics of genotype and phenotype in children with epilepsy and SCN9A gene mutation.Method:Epileptic patients who treated in the Pediatric Department of Guangdong Provincial People’s Hospital from June 2016 to May 2018 and detected SCN9A mutation by whole-exome sequencing,and mutations were validated using the Sanger sequencing method.Result:A total of 6 patients (3 boys and 3 girls) with SCN9A mutations were collected.Six SCN9A mutations were identified.All of them were heterozygous missense mutation and inherited from one of their parents,caused amino acid changes.Five mutations of them were distributed in highly conservative regions.The generalized tonic-clonic seizure:the most common seizure type was observed in 4 patients (66.7%),focal seizure was observed in 1 patient (16.7%),Atonic seizure was observed in 1 patient (16.7%).In 3 patients (50.0%),seizures manifested fever-sensitive.There were many clinical phenotypes,1 patient was diagnosed febrile seizures plus,1 patient with genetic epilepsy with febrile seizures plus,1 patient with Dravet syndrome,1 patient with frontal lobe epilepsy,2 patients with unclassified epilepsy.Conclusion:The features of patients with SCN9A mutations include that heterozygous missense mutations are dominant,and most of these mutations distribute in highly conservative regions,the main seizure type is the generalized seizure,most seizures manifeste fever-sensitive,the clinical phenotype spectrum is broad.