生殖医学杂志

目的 探讨13例SCN1A基因变异相关癫痫患儿的基因分型、临床特征与治疗结果。方法 回顾性分析2019年1月至2024年7月就诊于甘肃省妇幼保健院(甘肃省中心医院)的13例癫痫患儿，通过全外显子组测序结合Sanger测序验证进行基因检测，依据美国医学遗传学与基因组学学会(ACMG)发布的遗传变异分类标准与指南判定变异致病性。治疗方案采用个体化抗癫痫药物组合治疗，主要用药包括丙戊酸钠、左乙拉西坦及氯巴占等，对难治性病例联合生酮饮食治疗。记录患者的诊疗情况及家系检查资料等。结果 13例患儿中检测到的SCN1A变异分属于不同的基因变异，无义变异3种，移码变异2种，错义变异8种，其中5种变异为未报道的新变异。13种基因变异中的6种变异评级为致病性变异，其余7种评级为可能致病性变异。所有患儿经1～8种抗癫痫发作药物治疗，其中2例得到完全控制，5例治疗情况好转，6例治疗无效。结论 本研究丰富了SCN1A变异数据库，为本地区SCN1A变异导致的相关疾病患者的干预治疗、遗传咨询及生育指导提供了一定的基础性数据。

Objectives:To analyze the genotypes, clinical characteristics and treatment results of 13 children with epilepsy caused by SCN1A gene variation.Methods:This study retrospectively included 13 children with epilepsy who visited Gansu Provincial Maternity and Child Health Hospital(Gansu Provincial Central Hospital) from January 2019 to July 2024. Genetic testing was performed through whole exome sequencing combined with Sanger sequencing verification. The pathogenicity of the variation was determined in accordance with the Genetic Variation Classification Criteria and Guidelines issued by the American College of Medical Genetics and Genomics(ACMG). The individualized antiepileptic drug combination therapy strategy was used for the treatment. The main drugs included sodium valproate, levetiracetam and clobazan, etc. For refractory cases, ketogenic diet therapy was added. The diagnosis and treatment as well as the pedigree data of the patients were recorded.Results:The SCN1A gene detected in 13 children belonged to 13 different gene variants, including three nonsense variants, two frame-shift variants and eight missense variants, five of which were unreported new variants. Six of these 13 variants had pathogenicity ratings as pathogenic variants and seven were suspected pathogenic variants. After treatment with one to eight anti-seizure medications, two cases were completely controlled by treatment, five cases improved, and six cases failed.Conclusions:This study enriched the SCN1A gene variation database, and provided some basic data for intervention treatment, genetic counseling and fertility guidance for patients with SCN1A gene variation in the local area.