Beschreibung:
<jats:title>Abstract</jats:title><jats:p>Tuberous sclerosis complex (TSC) is an autosomal dominant disease caused by loss-of-function mutations in either of two tumor suppressor genes, <jats:italic>TSC1</jats:italic> and <jats:italic>TSC2</jats:italic>. These mutations lead to the growth of benign tumors and hamartomas in many organs, including those of the central nervous system, the skin, and the kidneys. To investigate the genotype-phenotype correlation, we performed sequence analysis of the <jats:italic>TSC1</jats:italic>/<jats:italic>2</jats:italic> genes using next-generation sequencing. We classified 30 patients with TSC whose pathogenic variants were identified into two groups: those with mutations producing premature termination codons (PTCs) and those with missense mutations. Then, we compared the phenotypes between the two groups. Patients with a PTC were significantly more likely to manifest the major symptoms of the diagnostic criteria than those without a PTC (<jats:italic>P</jats:italic> = 0.035). The frequencies of subependymal nodules (<jats:italic>P</jats:italic> = 0.026), cortical tubers (<jats:italic>P</jats:italic> = 0.026), and renal cysts (<jats:italic>P</jats:italic> = 0.026) were significantly higher in PTC-containing variants than in cases without a PTC. When the analyses were limited to renal angiomyolipoma (AML) cases with <jats:italic>TSC2</jats:italic> mutations, there was no difference in tumor size between cases with and without a PTC. However, the cases with a PTC showed a trend toward disease onset at a younger age and multiple tumors, and bilateral disease was observed in their AML lesions. TSC patients with PTC-producing mutations might potentially manifest more severe TSC phenotypes than those with missense mutations. A larger-scale study with appropriate samples deserves further investigation.</jats:p>