结节性硬化症致病基因及基因突变研究进展

Progress in studies of pathogenic gene of tuberous sclerosis complex

结节性硬化症(tuberous sclerosis complex,TSC)是一种常染色体显性遗传病,典型临床特征是癫痫、智能减退、面部血管纤维瘤及各系统的错构瘤。该病具有遗传异质性,由TSC1或TSC2基因突变引起。TSC1编码错构瘤蛋白(hamartin),TSC2编码马铃薯球蛋白(tuberin)。这两种蛋白质在组织中广泛表达,于体内形成Hamartin-Tuberin复合体,若TSC1或TSC2基因发生突变,则影响Hamartin-Tuberin二聚体功能,使mTOR复合物1(mTOR complex 1,mTORC1)信号转导通路异常激活,导致结节性硬化症的发生。目前研究证实该病与TSC1或TSC2基因突变有关。该文就结节性硬化症的致病基因及基因突变研究进展作一综述。

Tuberous sclerosis complex（TSC） is an autosomal dominant genetic disease, characterized by epilepsy, intellectual disability, facial angiofi bromas and development of hamartomas in several organs. The disease has a genetic heterogeneity, caused by mutations in one of two genes, namely TSC1 or TSC2 gene, which encodes hamartin and tuberin respectively. These two kinds of protein widely express in the organizations and form a heterodimer which lies at the crossroad of many signaling pathways. If mutations occur in either TSC1 or TSC2 gene, it would result in dysregulated mTORC1 activation, and fi nally leads to the occurrence of tuberous sclerosis complex. The current study confi rmed that TSC is caused by the mutations of TSC1 or TSC2 gene. This article reviews the research progress of TSC1 and TSC2 genes and their mutations.