探讨一个结节性硬化症(TSC)家系的遗传学病因。

选择2021年8月23日就诊于怀化市妇幼保健院产前诊断中心一孕12周胎儿，收集其TSC家系临床信息，运用全外显子测序筛查可疑致病位点，结合Sanger测序验证，确定致病位点并对胎儿进行产前诊断。

先证者(胎儿父亲)癫痫反复发作，背部、臀部多个大小不一色素斑，双侧侧脑室膜下多发小结节钙化灶，双肾多发高回声结节，肝脏多发血管平滑肌脂肪瘤；全外显子测序检测发现TSC2基因10号外显子存在c.968 T>C(p.F323S)杂合变异，临床诊断符合TSC。胎儿孕29^＋周、31^＋周超声检测均发现胎儿心脏、肾内、颅内多个强回声团，对胎儿及家庭成员进行Sanger测序验证发现胎儿变异位点与父亲一致，该变异在国内外数据库中均未收录，亦无相关文献报道。

根据先证者、胎儿临床资料以及测序结果家系验证分析，认为c．968 T>C(p.F323S)杂合变异是TSC2基因一个新的致病位点，是该家系的致病原因，为其遗传咨询和产前诊断提供了依据。

To explore the diagnostic features of the tuberous sclerosis complex (TSC) caused by the c. 968 T>C mutation in the TSC2 gene.

A 12-week-old fetus was selected from the Prenatal Diagnostic Center of Maternal and Child Health Care Hospital of Huaihua on August 23, 2021, and the clinical information on the family lineage of TSC was collected. The suspected pathogenic mutation was screened by whole-exome sequencing, and verified by Sanger sequencing to identify the pathogenic variant and prenatal diagnosis of the fetus.

The proband (fetus′ father) had recurrent epilepsy, multiple pigmented spots of varying sizes on the back and buttocks, multiple small nodular calcified foci under the bilateral ventricle membranes, multiple hyperechoic nodules in both kidneys, multiple vascular smooth muscle lipomas of the liver. Whole-exome sequencing revealed a heterozygous c. 968 T>C (p.F323S) variation in exon 10 of the TSC2 gene, which confirmed the clinical diagnosis of TSC. At 29 and 31 weeks of gestation, ultrasonography revealed many significant echogenic masses in the fetal heart, intrarenal and intracranial areas. The Sanger sequencing findings of the fetus and family members confirmed that the fetal variant was consistent with the father. This variant was neither included in local or international databases, nor reported in the literature.

Based on the proband and fetus′s clinical data, as well as familial validation analysis of the whole-exome sequencing results, the heterozygous variant c. 968 T>C (p.F323S) is thought to be a new harmful mutation in the TSC2 gene. It is the cause of the disease in this family lineage, which serves as the foundation for genetic counseling and prenatal diagnosis.