Purpose

To review the current genetic aspects of tuberous sclerosis complex.

Methods

Review of the literature.

Results

Tuberous sclerosis complex (TSC), a long known childhood-onset monogenic disorder, characterized by hamartoma formation affecting mainly the brain, heart, kidney, lung, and skin, is associated with a high morbidity burden and risk of a reduced life span. The identification of TSC1 and TSC2, as tumor suppressor genes causative of the disorder, led to the elucidation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway and its pivotal role in the pathogenesis of hamartoma formation. This knowledge was translated into standard clinical practice with the discovery of rapamycin, and additional analogues, as inhibitors of mTORC1.

Conclusion

Next-generation sequencing was proven to be fundamental to drive research of tumorigenesis in TSC, hopefully leading to new therapeutic options in the future.

中文翻译：

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结节性硬化症的遗传学：更新。

目的

回顾目前结节性硬化症的遗传方面。

方法

文献回顾。

结果

结节性硬化症 (TSC) 是一种长期已知的儿童期发病单基因疾病，其特征是主要影响大脑、心脏、肾脏、肺和皮肤的错构瘤形成，与高发病率负担和缩短寿命的风险有关。鉴定 TSC1 和 TSC2 作为导致该疾病的肿瘤抑制基因，有助于阐明哺乳动物雷帕霉素复合物 1 (mTORC1) 信号通路靶标及其在错构瘤形成发病机制中的关键作用。随着雷帕霉素和其他类似物作为 mTORC1 抑制剂的发现，这些知识被转化为标准临床实践。

结论

下一代测序被证明是推动 TSC 肿瘤发生研究的基础，有望在未来带来新的治疗选择。