Clinical diagnostic characteristics of children with epilepsy combined with febrile seizures plus caused by SCN1A gene mutation
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摘要:
目的 研究SCN1A基因突变致癫痫伴热性惊厥附加症患儿的临床诊断学特征，为诊疗方案的制定提供理论参考。 方法 选择2018年5月—2021年5月浙江大学医学院附属金华医院接诊的46例癫痫伴热性惊厥附加症患儿作为研究对象，采用二代高通量基因测序仪检测患儿SCN1A基因突变情况，对比不同SCN1A基因分型患者的临床诊断学特征。 结果 46例癫痫伴热性惊厥附加症患儿的初次发病年龄为12~18个月，其中SCN1A基因突变阳性36例，突变发生率为78.26%，包括18例错义突变、18例截断突变，截断突变包括3例(8.33%)剪切突变、10例(27.78%)移码突变、2例(5.56%)大片段缺失及3例(8.33%)无义突变。受检患儿SCN1A基因发现杂合突变(核苷酸变化为c.1499A＞G)，编码区第1 499号核苷酸由G变成T，导致第946号氨基酸由Arg变成了Cys，即p.(Arg946Cys)；受检患儿SCN1A基因发现杂合突变(核苷酸变化为c.2891T＞G)，编码区第2 891号核苷酸由T变成G，导致第542号氨基酸由原来的亮氨酸(L)变成了精氨酸(R)，即p.L542R，此突变属于错义突变；且突变位点分布在钠通道α亚单位蛋白结构域DⅡS5-S6连接环处，不属于多态性变化。 结论 癫痫伴热性惊厥附加症患儿存在SCN1A基因高突变风险，且热性惊厥附加症患儿的表型特征与SCN1A基因突变的类型和位置密切相关，可以为临床诊疗提供靶向参考。 Abstract:Objective To study the clinical diagnostic characteristics of children with epilepsy combined with febrile seizures plus (EFS+) caused by SCN1A gene mutation and to provide a theoretical reference for diagnosis and treatment. Methods A total of 46 children with EFS+ who were admitted to Jinhua Hospital Affiliated to Medical College of Zhejiang University from May 2018 to May 2021 were selected as participants. The second-generation high-throughput gene sequencer was used to detect SCN1A gene mutations in children, and the clinical diagnostic characteristics of patients with different SCN1A genotypes were compared. Results A total of 46 children with EFS+ had an initial age of 12-18 months. Among them, 36 cases of SCN1A gene mutation were positive, and the mutation rate was 78.26%, including 18 cases of mis-sense mutations, 18 cases of truncation mutations. Truncation mutations included 3 cases (8.33%) of splicing mutations, 10 cases (27.78%) of frameshift mutations, 2 cases (5.56%) of large fragment deletions and 3 cases (8.33%) of non-sense mutations. A heterozygous mutation (nucleotide change c.1499A > G) was found in the SCN1A gene of the tested child, and the 1499th nucleotide in the coding region was changed from G to T, resulting in the 946th amino acid being changed from Arg to Cys, that was p.(Arg946Cys). A heterozygous mutation was found in the SCN1A gene of the tested child (nucleotide change was c.2891T > G), and the 2891st nucleotide in the coding region was changed from T to G, which changed amino acid 542 from the original leucine (L) to arginine (R), namely, p.L542R. This mutation was a mis-sense mutation. The mutation sites were distributed in the DⅡS5-S6 junction loop of the sodium channel alpha subunit protein domain, which was not a polymorphic change. Conclusion Children with EFS+ are at high risk of SCN1A gene mutations, and the phenotypic characteristics of children with febrile seizures plus are closely related to the type and location of SCN1A gene mutations, which can provide a targeted reference for clinical diagnosis and treatment. -
Key words:
- Febrile seizures plus /
- Gene mutation /
- Epilepsy /
- Clinical features /
- Children
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表 1 46例癫痫伴热性惊厥附加症患儿基因测定结果
突变类型 例(%) 错义突变 核心编码区 13(28.26) 其他编码区 5(10.87) 截断突变 剪切突变 3(6.52) 移码突变 10(21.74) 大片段缺失 2(4.35) 无义突变 3(6.52) SCN1A基因突变 36(78.26) 
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