Department of Pediatrics, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
Department of Pediatrics, Shantou Central Hospital, Shantou, People's Republic of China.
Clin Genet. 2024 Aug;106(2):140-149. doi: 10.1111/cge.14519. Epub 2024 Mar 11.
Genotype and clinical phenotype analyses of 128 children were performed based on whole exome sequencing (WES), providing a reference for the provision of genetic counseling and the precise diagnosis and treatment of epilepsy. A total of 128 children with unexplained epilepsy were included in this study, and all their clinical data were analyzed. The children's treatments, epilepsy control, and neurodevelopmental levels were regularly followed up every 3 months. The genetic diagnostic yield of the 128 children with epilepsy is 50.8%, with an SNV diagnostic yield of 39.8% and a CNV diagnostic yield of 12.5%. Among the 128 children with epilepsy, 57.0% had onset of epilepsy in infancy, 25.8% have more than two clinical seizure forms, 62.5% require two or more anti-epileptic drug treatments, and 72.7% of the children have varying degrees of psychomotor development retardation. There are significant differences between ages of onset, neurodevelopmental levels and the presence of drug resistance in the genetic diagnostic yield (all p < 0.05). The 52 pathogenic/likely pathogenic SNVs involve 31 genes, with genes encoding ion channels having the largest number of mutations (30.8%). There were 16 cases of pathogenic/possibly pathogenic CNVs, among which the main proportions of CNVs were located in chromosome 15 and chromosome 16. Trio-WES is an essential tool for the genetic diagnosis of unexplained epilepsy, with a genetic diagnostic yield of up to 50.8%. Early genetic testing can provide an initiate appropriate therapies and accurate molecular diagnosis.
对 128 例不明原因癫痫患儿进行全外显子组测序（WES）的基因型和临床表型分析，为遗传咨询、癫痫的精准诊断和治疗提供参考。收集 128 例不明原因癫痫患儿的临床资料进行分析，定期每 3 个月随访患儿的治疗、癫痫控制及神经发育水平。128 例癫痫患儿的基因诊断率为 50.8%，其中 SNV 诊断率为 39.8%，CNV 诊断率为 12.5%。128 例癫痫患儿中，57.0%起病于婴幼儿期，25.8%有两种以上临床发作形式，62.5%需要两种及以上抗癫痫药物治疗，72.7%的患儿存在不同程度的精神运动发育迟缓。基因诊断率在起病年龄、神经发育水平及耐药性方面差异均有统计学意义（均 P<0.05）。52 个致病性/可能致病性 SNVs 涉及 31 个基因，其中编码离子通道的基因发生突变最多（30.8%）。致病性/可能致病性 CNVs 共 16 例，其中以 CNVs 位于染色体 15 和染色体 16 为主。Trio-WES 是不明原因癫痫遗传诊断的重要手段，基因诊断率可达 50.8%。早期基因检测可提供起始适当的治疗和准确的分子诊断。
