Tuberous sclerosis with a novel TSC1 variant: a case report

Abstract Background Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder characterized by multisystem hamartomas. Pathogenic variants in TSC1 or TSC2 are causative, and the identification of novel variants expands genotype–phenotype correlations and informs clinical management. Methods We evaluated a 10-year-old Albanian girl presenting with seizures and hypomelanotic macules. Clinical, radiological, and genetic analyses were performed. Peripheral blood DNA was sequenced for all exons of TSC1 and TSC2 using PCR and Sanger sequencing. Results Magnetic resonance imaging revealed multiple cortical and subcortical lesions, as well as a nodular ependymal lesion near the foramen of Monro. Genetic analysis identified a novel heterozygous nonsense variant in TSC1, c.488C > G; p.(Ser163Ter). This variant was absent from gnomAD, 1000 Genomes, ClinVar, and the parents’ DNA, indicating a de novo pathogenic mutation predicted to truncate hamartin. Conclusions We report the first description of the TSC1 variant c.488C > G; p.(Ser163Ter) associated with TSC. This finding underscores the importance of comprehensive genetic screening for accurate diagnosis, risk assessment, and patient management. Early identification of novel pathogenic variants facilitates genetic counseling and supports tailored long-term follow-up.