Genetic and Clinical Features of Tuberous Sclerosis Patients from the Republic of Bashkortostan

Tuberous sclerosis (TS) is one of the most common hereditary tumor syndromes, occurring with an average incidence of 1 in 9,000 newborns worldwide. The disease manifests itself through the development of tumors of the brain, kidneys, heart, lungs, and skin, along with characteristic depigmented spots. Tuberous sclerosis is caused by germline variants in the TSC1 (encoding hamartin) and TSC2 (encoding tuberin) genes. The hamartin-tuberin protein complex, together with the TBC1D7 molecule, inhibits the serine/threonine protein kinase mTORC1 (mammalian target of rapamycin complex 1), which is essential for cell proliferation and growth. Accordingly, the use of mTOR inhibitors in the treatment of tuberous sclerosis affects the pathogenesis of the disease and tumor development. Meta-analyses have confirmed the efficacy of mTOR inhibitors in the treatment of tuberous sclerosis, making molecular genetic confirmation of the diagnosis essential for treatment planning. To analyze the clinical and genetic characteristics of tuberous sclerosis in the Republic of Bashkortostan (RB). A retrospective study of patients with tuberous sclerosis registered at the Republican Medical Genetic Center was conducted. 23 programs were used to assess the pathogenicity of newly discovered variants. The odds ratio (OR) was calculated manually using the formula: OR = (A × D)/(B × C). Currently, 88 cases of tuberous sclerosis have been registered in RB, of which 5 patients had pathogenic variants in the TSC1 gene, 19 had pathogenic variants in the TSC2 gene, and 4 people had extensive deletions of the TSC2 gene. Compared with global data, a statistically significantly lower incidence of subependymal nodules, cortical tubers, renal angiomyolipomas, gingival fibromas, pulmonary lymphangiomyomatosis, facial angiofibromas, cognitive impairment, and autism was determined. The significantly lower incidence of brain and internal organ tumors may be due to genetic factors affecting the disease in the region. In 28 of 88 patients with tuberous sclerosis (33%), the diagnosis was confirmed at the genetic level, which forms the basis for treatment with mTOR inhibitors, which is being administered to 8 patients.