短指(趾)症及指(趾)骨发育的分子调控机制
收稿日期: 2019-06-27
修回日期: 2019-08-09
网络出版日期: 2019-10-15
基金资助
西部资源生物与现代生物技术教育部重点实验室开放研究基金项目资助编号：(ZSK2018010)
Brachydactyly and the molecular mechanisms of digit formation
Received date: 2019-06-27
Revised date: 2019-08-09
Online published: 2019-10-15
Supported by
Supported by the Opening Foundation of Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education No(ZSK2018010)
短指(趾)症(brachydactyly, BD)是一类指(趾)骨或掌(跖)骨的异常缩短或缺失而造成的手/足畸形病变。从临床表型上短指(趾)症可以分为单纯型短指(趾)症以及包含短指(趾)症状的综合征,其中单纯型短指(趾)症又分为5种类型：BDA、BDB、BDC、BDD和BDE,而每一类型又分为不同的亚型。作为一类重要的分子疾病家族,随着对每种短指(趾)症的深入研究,大多数单纯型短指(趾)症和部分综合征的致病基因及其分子机制逐渐被发现。虽然短指(趾)症在表型上高度多样化,但在分子水平上这些致病基因主要影响Hedgehog、NOTCH、WNT和BMP等信号传导通路。这些信号传导通路组成了一个复杂的信号调控网络,在指(趾)骨及关节的不同发育阶段发挥着不同的作用,其中BMP信号传导通路扮演着至为关键的角色。本文在目前对短指(趾)症的分类基础上,详细综述了短指(趾)症相关致病基因及所影响的信号通路等方面的最新进展,旨在探讨指(趾)骨形成的分子机制,以期为短指(趾)症的临床诊断以及人类骨骼发育的分子调控机制研究提供参考。
吕赵劼, 王志浩, 卢淑娴, 刘沛蓉, 田静 . 短指(趾)症及指(趾)骨发育的分子调控机制[J]. 遗传, 2019 , 41(12) : 1073 -1083 . DOI: 10.16288/j.yczz.19-100
Brachydactyly (BD) is a type of hand/foot malformation caused by the abnormal shortening or missing phalanges and/or metacarpals/metatarsals. BD most often occurs as an isolated trait, but can also occur as part of complex malformation syndromes. According to the patterns of affected digits, isolated BD can be divided into five groups: BDA, BDB, BDC, BDD, and BDE with individual subtypes. As an important molecular disease family, the pathogenic genes and molecular mechanisms of most isolated BD forms and some complicated syndromes are elucidated. Although BDs are highly diversified in phenotypes, at the molecular levels these pathogenic genes mainly affect several important signaling pathways: Hedgehog, NOTCH, WNT and BMP. These pathways form a complex signaling network and play different roles in different stages of the digit and joint development, in which BMP signaling pathway occupies a central position. Based on the current classification of BDs, this review summarizes the latest progress in the pathogenesis of BDs and the signaling pathways involved. The purpose of this review is to explore the molecular mechanisms of digit formation, which will provide references for the clinical diagnosis of BD, and the understanding of molecular mechanism of human bone development.
Key words： brachydactyly; signaling pathways; Hedgehog; NOTCH; WNT; BMP
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