摘要：

结节性硬化症是累及多器官系统的常染色体显性遗传性疾病，由TSC1 或TSC2 基因变异所致，具有高度遗传异质性。TSC1 和TSC2 基因编码的蛋白形成一种复合物，作用于雷帕霉素机制靶蛋白（mTOR）信号转导通路，抑制蛋白合成，调节神经元迁移和增殖、轴突形成、突触可塑性。TSC 基因突变使mTOR 信号转导通路异常激活，导致结节性硬化症。2012 年的国际结节性硬化症共识大会修订诊断标准，增加基因诊断并将其作为独立的诊断标准。同时，近年开展多项针对mTOR 蛋白抑制剂的临床研究，证实其可以有效治疗结节性硬化症相关室管膜下巨细胞型星形细胞瘤、肾血管平滑肌脂肪瘤和难治性癫痫。

关键词: 结节性硬化症, 遗传学, 诊断, 治疗, 综述

Abstract:

Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disorder that variably affects multiple organs. It is caused by TSC1 or TSC2 gene variation and has a high genetic heterogeneity. The proteins encoded by TSC1 and TSC2 genes form a complex which mediate through the mechanistic target of rapamycin (mTOR), thereby inhibiting protein synthesis, meanwhile regulating neuronal migration and proliferation, axon formation and synaptic plasticity. TSC gene variation results in overreaction of mTOR pathway and leads to the occurrence of TSC. Based on studies of the pathogenesis of this disease, the diagnostic criteria of TSC was revised in 2012 by International Tuberous Sclerosis Complex Consensus Group, and gene diagnosis was added as an independent diagnostic criteria. Recently, a number of clinical trials of mTOR inhibitors have confirmed their efficacy in treatment of subependymal giant cell astrocytoma (SEGA), renal angiomyolipoma (AML) and refractory epilepsy of TSC.

Key words: Tuberous sclerosis, Genetics, Diagnosis, Therapy, Review