Clinical and genetic characterization of a novel pathogenic TSC1 variant in a familial case of tuberous sclerosis complex

Abstract

Tuberous sclerosis complex (TSC) is a rare autosomal dominant disease. TSC exhibits significant genotypic and phenotypic heterogeneity. There are considerable differences in the clinical manifestations of the disease between patients in the same family or different families, resulting in a more complex clinical diagnosis. We analyzed the genotype and phenotype characteristics of a familial TSC through genetic testing. The causative genes are divided into TSC1 and TSC2 genes. Cases transmitted within families often result in mild to moderate illnesses, which sometimes fail to meet all diagnostic criteria, and exhibit a higher frequency of changes in the TSC1 gene. We reported a novel pathogenic TSC1 variant in a familial case of TSC. The principal clinical manifestations in both brothers included epilepsy, the presence of skin depigmentation spots, and developmental delay. The mother experienced sporadic convulsions and exhibited patches resembling those found on a shark's skin, but without depigmentation spots. Her intellectual and motor development were both normal. The father showed no signs of abnormal clinical symptoms. Genetic testing identified a novel pathogenic variant in the TSC1 gene, which was present in both brothers and their mother but not in the father. This discovery not only broadened the understanding of the TSC1 gene's mutation spectrum but also contributed to the discourse on the intricate connection between genotype and the clinical expression of TSC.