TSC1 and TSC2 Gene Mutations in Chinese Tuberous Sclerosis Complex Patients Clinically Characterized by Epilepsy.

Abstract

Objective: Tuberous sclerosis complex (TSC) is a multisystem disease. Variants in the TSC1 and TSC2 genes have been reported to be associated with TSC and are considered pathogenic. The purpose of this study was to determine the genetic mutations and expression patterns of TSC1 and TSC2 in 21 Chinese patients suffering from TSC who were clinically characterized by epilepsy. Methods: Peripheral blood samples were taken from 21 patients, their parents, and other family members. Their TSC1 and TSC2 genes were sequenced through next-generation sequencing to identify all variants. Results: We identified variants in 17/21 patients in either their TSC1 or TSC2 genes: 6 patients had TSC1 mutations and 11 had TSC2 mutations. There were 13 spontaneous mutations, and 3 that had been inherited from a parent. The mutations were classified by types: there were three missense mutations, five frameshift mutations, two splice site mutations, four nonsense mutations, two single codon deletions resulting the loss of an amino acid, and one large fragment deletion. Six of the mutations have not been previously reported. Conclusion: The genotypic analysis of Chinese TSC patients who are clinically characterized by epilepsy can potentially be useful for genetic counseling and prenatal diagnoses for patients and their families.