短指(趾)症及指(趾)骨发育的分子调控机制

doi:10.16288/j.yczz.19-100

遗传 ›› 2019, Vol. 41 ›› Issue (12): 1073-1083.doi: 10.16288/j.yczz.19-100

• 综述 • 下一篇

短指(趾)症及指(趾)骨发育的分子调控机制

吕赵劼, 王志浩, 卢淑娴, 刘沛蓉, 田静()

西北大学生命科学学院,西部资源生物与现代生物技术教育部重点实验室,西安 710069

收稿日期:2019-06-27 修回日期:2019-08-09 出版日期:2019-12-20 发布日期:2019-10-15
通讯作者: 田静 E-mail:tianjing@nwu.edu.cn
作者简介:吕赵劼,硕士研究生,专业方向：人类遗传与发育生物学。E-mail: ZhaojieLyu@outlook.com
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

Zhaojie Lyu, Zhihao Wang, Shuxian Lu, Peirong Liu, Jing Tian()

Key Laboratory of Resource Biology and Biotechnology in Western China(Ministry of Education), College of Life Sciences, Northwest University, Xi’an 710069, China

Received:2019-06-27 Revised:2019-08-09 Online:2019-12-20 Published:2019-10-15
Contact: Tian Jing E-mail:tianjing@nwu.edu.cn
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)

摘要/Abstract

摘要：

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。

关键词: 短指(趾)症, 信号传导通路, Hedgehog, NOTCH, WNT, BMP

Abstract:

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

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.

Zhaojie Lyu, Zhihao Wang, Shuxian Lu, Peirong Liu, Jing Tian. Brachydactyly and the molecular mechanisms of digit formation[J]. Hereditas(Beijing), 2019, 41(12): 1073-1083.

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	疾病名称	MIM	致病基因	基因定位	参考文献
单纯型短指(趾)症	BDA1	112 500	IHH、GDF5和BMP1RB	2q35~q36、20q11和4q21~20	[10~12]
	BDA2	112 600	BMPR1B、GDF5和BMP2	4q21~20、20q11和20p12	[13~15]
	BDA3	112 700	暂无	暂无	[1,2]
	BDA4	112 800	暂无	暂无	[1,2]
	BDB1	113 000	ROR2	9q22	[5]
	BDB2	611 377	NOG	17q22	[6]
	BDC	113 100	GDF5	20q11	[7]
	BDD	113 200	HOXD13	2q31.1	[8]
	BDE1	113 300	HOXD13	2q31.1	[8]
	BDE2	613 328	PTHLH	12p11.22	[9]
部分短指 (趾)综合征	短指(趾)-高血压综合征	112 410	PDE3A	12p12.2	[3]
	Rubinstein-Taybi综合征	180 849	CREBBP	16p13.3	[3]
	Adams-Olive 综合征	100 300	ARHGAP31	3q13.32~q13.33	[3]
	Catel-Manzke综合征	616 145	TGDS	13q32.1	[3]
	Feingold 综合征	164 280	MYCN	2p24.3	[3]
	Du Pan 综合征	228 900	GDF5	20q11.2	[3]
	Robinow 综合征	268 310	ROR2	9q22	[16,17]
	Temtamy轴前短指综合征	605 282	CHSY1	15q26.3	[18]

短指(趾)症及指(趾)骨发育的分子调控机制

Brachydactyly and the molecular mechanisms of digit formation

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