Analysis of TSC1 and TSC2 genes and evaluation of phenotypic correlations with tuberous sclerosis

Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by the formation of benign tumors in various organs, particularly in the central nervous system. We aimed to delineate the molecular profile of Turkish individuals diagnosed with TSC by analyzing the TSC1 and TSC2 genes using next-generation sequencing (NGS). Sophia Genetics' Sophia Inherited Disease Panel was used to perform NGS on 22 individuals diagnosed with TSC and to identify pathogenic variants in the TSC1 and TSC2 genes. Among the 22 cases, mutations were found in 3 (13.6%) for TSC1 and in 16 (73%) for TSC2, while 3 (13.6%) exhibited no detectable mutations. Notably, one individual with a TSC2 mutation presented with angiofibroma, ungual fibroma, and pitted dental enamel, while another had cardiac rhabdomyoma. Autism spectrum disorders were observed in 6 (27%) with TSC2 mutations, including one with autistic behavior. Abnormal motor development was noted in 3 (13.6%), of which 2 had TSC2 mutations. Severe intellectual disability was found in 3 (13.6%) with TSC2 mutations, and developmental delay was seen in 2 (9%) with TSC2 mutations. Epileptic encephalopathy occurred in 3 (13.6%), with 2 having TSC2 mutations. Additionally, 6 (27%) exhibited drug resistance for focal seizures, with 5 of them having TSC2 mutations. These findings are consistent with other research indicating that TSC2 mutations are associated with a more severe phenotypic range compared to TSC1 mutations. Moreover, our analysis showed that some people with TSC1/TSC2 mutations did not match diagnostic criteria. This highlights the importance of genetic testing and molecular profiling in understanding the clinical variability and aiding in the management of TSC patients.