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.