遗传缺陷致中枢性性早熟病因学的研究新进展

Recent advances in the genetic etiology of central precocious puberty

摘要:

中枢性性早熟（central precocious puberty, CPP）是下丘脑-垂体-性腺轴提早激活所导致的发育异常性疾病，其发病率快速增加，但发病机制尚未完全明确。既往研究发现KISS1R、KISS1基因的功能获得性突变，以及MKRN3、LIN28和DLK1基因的功能缺失性突变可导致青春发育期启动时间提前。新近研究发现表观遗传因素如DNA甲基化、微小核糖核酸在促性腺激素释放激素神经元的调控中起重要作用；基因网络中多个变异基因的协同作用也可影响青春发育启动。该文综述了导致CPP的遗传学病因进展及其致病机制。

Abstract:

Central precocious puberty (CPP) is a developmental disorder caused by early activation of the hypothalamic-pituitary-gonadal axis. The incidence of CPP is rapidly increasing, but the underlying mechanisms are not fully understood. Previous studies have shown that gain-of-function mutations in the KISS1R and KISS1 genes and loss-of-function mutations in the MKRN3, LIN28, and DLK1 genes may lead to early initiation of pubertal development. Recent research has also revealed the significant role of epigenetic factors such as DNA methylation and microRNAs in the regulation of gonadotropin-releasing hormone neurons, as well as the modulating effect of gene networks involving multiple variant genes on pubertal initiation. This review summarizes the genetic etiology and pathogenic mechanisms underlying CPP.