非综合征性先天性关节融合的遗传学研究进展  

Advances in genetic research on Non-syndromic congenital joint synostosis

作　　者：邓媚 谌芳 杨永佳 Deng Mei;Shen Fang;Yang Yongjia(Institute of Pediatrics,South China University,Department of Medical Genetics,Hunan Provincial Children′s Hospital,Changsha,Hunan 410007,China)

机构地区：[1]南华大学儿科学院·湖南省儿童医院医学遗传科,长沙410007

出　　处：《中华医学遗传学杂志》2024年第8期1001-1009,共9页Chinese Journal of Medical Genetics

基　　金：湖南省自然科学基金(2023JJ40343);湖南省卫健委科研基金(B202306048930);国家自然科学基金(31501017)。

摘　　要：先天性关节融合(CJS)是胚胎发育过程中关节形态发生失败所导致的异常,在临床上又分为综合征性(sCJS)和非综合征性(nsCJS)。常见的sCJS包括染色体病(如克氏综合征等)和单基因病(如Apert/Pfeiffer/Crouzon综合征、Holt-Oram综合征、Ehlers-Danlos综合征和尺桡骨融合伴血小板减少症等),可累及多个系统及器官,而nsCJS仅累及单一或多个关节。迄今为止,已发现7个基因(NOG、GDF5、FGF9、GDF6、FGF16、SMAD6和MECOM)的变异可能导致nsCJS。本文聚焦于这些基因,并对nsCJS的临床表型、遗传模式、常见变异及其作用机制进行文献回顾,同时通过对关节形态发生的相关信号通路进行分析,探讨可能导致nsCJS的其他候选基因。Congenital joint synostosis(CJS)is a functional impairment resulting from failure in joint morphogenesis during embryonic development.Clinically,it may be classified as syndromic(sCJS)and non-syndromic(nsCJS)disorders.Common sCJS include chromosomal disorders such as Klinefelter syndrome and single-gene disorders like Apert/Pfeiffer/Crouzon syndromes,Holt-Oram syndrome,Ehlers-Danlos syndrome,and Radial-ulnar synostosis with thrombocytopenia,presenting with multiple system/organ anomalies.By contrast,nsCJS manifest with only joint abnormalities,affecting one or multiple joints.This review has focused on human nsCJS and its genetic etiology.To date,variants in seven genes(NOG,GDF5,FGF9,GDF6,FGF16,SMAD6,and MECOM)have been identified as causative factors for nsCJS.This review has focused on such genes and provided a comprehensive review for the clinical phenotypes,genetic patterns,common variants,and underlying mechanisms associated with nsCJS based on a literature review.In addition,it has also analyzed other candidate genes for nsCJS within the context of relevant signaling pathways involved in joint morphogenesis.

关 键 词：关节形态发生 非综合征性先天性关节融合 NOG基因 GDF5基因 GDF6基因 FGF9基因 FGF16基因 SMAD6基因 MECOM基因 

分 类 号：R726.8[医药卫生—儿科]