Praticò Andrea Domenico, Di Napoli Claudia, Salafia Stefania, Dammino Edoardo, Piccione Maria, Calì Francesco, Scifo Renato, Vecchio Michele, Zonta Andrea, Bonsignore Maria, Elia Maurizio, Lo Bianco Manuela, Polizzi Agata, Ruggieri Martino
Chair of Pediatrics, Department of Medicine and Surgery, University Kore of Enna, Enna, Italy.
Chair of Genetics, Department of Medicine and Surgery, University Kore of Enna, Enna, Italy.
Sci Rep. 2025 Jun 27;15(1):20347. doi: 10.1038/s41598-025-04718-6.
Tuberous Sclerosis Complex (TSC) is an autosomal dominant disorder characterized by widespread hamartomas and prominent neurological involvement. It results from pathogenic variants in the TSC1 or TSC2 genes, leading to hyperactivation of the mTOR pathway and consequent dysregulation of cell growth. These tumor suppressor genes encode hamartin and tuberin, proteins critical for regulating cell proliferation, neuronal excitability and synaptogenesis. In this retrospective study, we analyzed clinical, genetic and radiological features of 81 TSC patients from Sicily, focusing on genotype-phenotype correlations and intergroup comparisons. Pathogenic TSC2 variants were more common than pathogenic TSC1 variants (61.7% vs. 38.3%). Patients with pathogenic TSC2 variants tended to exhibit a higher frequency of weekly seizures, a higher prevalence of infantile spasms and hypsarrhythmia compared to those with pathogenic TSC1 variants, consistent with a more severe phenotype. Interestingly, TSC1 patients exhibited a higher incidence of radial bands, while TSC2 patients harbored a larger average size of tubers and subependymal nodules. Cognitive and behavioral disorders were similarly distributed, although TSC1 patients had higher rates of normal or borderline cognitive function, while TSC2 patients had more severe neuropsychiatric profiles compared to TSC1. To our knowledge, this is the first comprehensive TSC1 and TSC2 mutational analysis and genotype-phenotype correlation study carried out in a large cohort of Sicilian patients affected by TSC. Our findings contribute to regional and global data on TSC, emphasizing the utility of genotype-informed management strategies.
结节性硬化症（TSC）是一种常染色体显性疾病，其特征为广泛的错构瘤和显著的神经受累。它由TSC1或TSC2基因的致病变异引起，导致mTOR通路的过度激活以及随之而来的细胞生长失调。这些肿瘤抑制基因编码错构瘤蛋白和结节蛋白，这两种蛋白质对于调节细胞增殖、神经元兴奋性和突触形成至关重要。在这项回顾性研究中，我们分析了来自西西里岛的81例TSC患者的临床、遗传和放射学特征，重点关注基因型-表型相关性和组间比较。致病性TSC2变异比致病性TSC1变异更常见（61.7%对38.3%）。与携带致病性TSC1变异的患者相比，携带致病性TSC2变异的患者每周癫痫发作的频率更高，婴儿痉挛症和高度节律失调的患病率更高，这与更严重的表型一致。有趣的是，TSC1患者放射状带的发生率更高，而TSC2患者的结节和室管膜下结节的平均尺寸更大。认知和行为障碍的分布相似，尽管TSC1患者正常或临界认知功能的比例更高，而与TSC1患者相比，TSC2患者的神经精神状况更严重。据我们所知，这是在一大群受TSC影响的西西里患者中进行的首次全面的TSC1和TSC2突变分析以及基因型-表型相关性研究。我们的研究结果为关于TSC的区域和全球数据做出了贡献，强调了基于基因型的管理策略的实用性。
