背景:发育性髋关节发育不良(DDH)是一种复杂的发育畸形,其发病机制和易感性相关基因尚未阐明。本系统综述了目前有关DDH相关基因突变的文献,动物模型实验,和DDH的表观遗传变化。
方法:我们在Medline中对相关文献进行了全面搜索,Scopus,科克伦,和ScienceDirect数据库涵盖1991年10月至2021年10月。我们分析了纳入研究的基本信息,并总结了DDH相关突变位点,动物模型实验,和与DDH相关的表观遗传变化。
结果:共63项研究纳入分析,其中54个涉及基因突变的检测,7介绍了动物实验的细节,和6个是表观遗传学研究。无基因突变与DDH的发病机制明确相关,包括染色体1、17和20上研究最频繁的基因。大多数基因相关研究是在中国汉族或北美人群中进行的,这些研究的质量是中等或低。在最多的研究中检查了GDF5,比值比>10的突变位点位于3号、9号和13号染色体上。在动物实验中发现了六个突变(即,CX3CR1、GDF5、PAPPA2、TENM3、UFSP2和WISP3)。关于DDH的表观遗传学研究主要集中在GDF5启动子甲基化,三种微小RNA(miRNA),和长链非编码RNA。此外,还有一项miRNA和mRNA测序的基因检测.
结论:DDH是一种复杂的关节畸形,具有相当大的遗传成分,其早期诊断对预防疾病具有重要意义。目前,目前尚未发现明显参与DDH发病机制的基因。与这种情况相关的突变研究正朝着动物模型体内实验的方向发展,以鉴定DDH易感基因和表观遗传学分析,从而为其发病机理提供新的见解。在未来,遗传分析可能会改善问题。
BACKGROUND: Developmental dysplasia of the hip (DDH) is a complex developmental deformity whose pathogenesis and susceptibility-related genes have yet to be elucidated. This systematic
review summarizes the current literature on DDH-related gene mutations, animal model experiments, and epigenetic changes in DDH.
METHODS: We performed a comprehensive search of relevant documents in the Medline, Scopus, Cochrane, and ScienceDirect databases covering the period from October 1991 to October 2021. We analyzed basic information on the included studies and summarized the DDH-related mutation sites, animal model experiments, and epigenetic changes associated with DDH.
RESULTS: A total of 63 studies were included in the analysis, of which 54 dealt with the detection of gene mutations, 7 presented details of animal experiments, and 6 were epigenetic studies. No genetic mutations were clearly related to the pathogenesis of DDH, including the most frequently studied genes on chromosomes 1, 17, and 20. Most gene-related studies were performed in Han Chinese or North American populations, and the quality of these studies was medium or low. GDF5 was examined in the greatest number of studies, and mutation sites with odds ratios > 10 were located on chromosomes 3, 9, and 13. Six mutations were found in animal experiments (i.e., CX3CR1, GDF5, PAPPA2, TENM3, UFSP2, and WISP3). Epigenetics research on DDH has focused on GDF5 promoter methylation, three microRNAs (miRNAs), and long noncoding RNAs. In addition, there was also a genetic test for miRNA and mRNA sequencing.
CONCLUSIONS: DDH is a complex joint deformity with a considerable genetic component whose early diagnosis is significant for preventing disease. At present, no genes clearly involved in the pathogenesis of DDH have been identified. Research on mutations associated with this condition is progressing in the direction of in vivo experiments in animal models to identify DDH susceptibility genes and epigenetics analyses to provide novel insights into its pathogenesis. In the future, genetic profiling may improve matters.