目的 探讨2例结节性硬化症(TSC)患儿的临床表现及基因变异特点。 方法 选取2020年6月至2021年7月于郑州大学附属儿童医院就诊的2例TSC患儿为研究对象。收集2例患儿的临床资料，采用全外显子组测序(WES)筛选患儿的致病基因，针对可疑变异位点，进行Sanger测序家系验证。 结果 患儿1为7月29日龄男性，患儿2为2岁6月龄男性。2例患儿均表现为癫痫发作和多发性色素脱失斑。基因检测结果显示2例患儿分别携带TSC2基因c.3239_3240insA和c.3330delC新发变异，既往均未见报道，根据美国医学遗传学和基因组学学会相关指南，均评级为致病性变异(PVS1+PS2+PM2_Supporting)。 结论 本研究明确2例TSC患儿的遗传学病因，丰富了中国人群TSC的表型和基因变异谱。 Objective To explore the clinical characteristics and genetic variants in two children with Tuberous sclerosis complex (TSC). Methods Two children who had presented at the Children′s Hospital Affiliated to Zhengzhou University respectively in June 2020 and July 2021 were selected as the study subjects. Clinical data of the children were collected, and potential pathogenic variants were screened by whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of their family members. Results Child 1 was a 7-month-and-29-day-old male, and child 2 was a 2-year-and-6-month-old male. Both children had shown symptoms of epileptic seizures and multiple hypomelanotic macules. Genetic testing revealed that both children had harbored de novo variants of the TSC2 gene, namely c. 3239_3240insA and c. 3330delC, which were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion This study has uncovered the genetic etiology for two children with TSC. Above findings have also enriched the phenotypic and mutational spectrum of TSC in the Chinese population.
Abstract
Objective To explore the clinical characteristics and genetic variants in two children with Tuberous sclerosis complex (TSC). Methods Two children who had presented at the Children′s Hospital Affiliated to Zhengzhou University respectively in June 2020 and July 2021 were selected as the study subjects. Clinical data of the children were collected, and potential pathogenic variants were screened by whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of their family members. Results Child 1 was a 7-month-and-29-day-old male, and child 2 was a 2-year-and-6-month-old male. Both children had shown symptoms of epileptic seizures and multiple hypomelanotic macules. Genetic testing revealed that both children had harbored de novo variants of the TSC2 gene, namely c. 3239_3240insA and c. 3330delC, which were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion This study has uncovered the genetic etiology for two children with TSC. Above findings have also enriched the phenotypic and mutational spectrum of TSC in the Chinese population.
关键词
结节性硬化症/TSC2基因/新发变异
Key words
Tuberous sclerosis complex/TSC2 gene/De novo variant
万方数据