先天性心脏病相关TBX5突变的研究进展

Research progress on congenital heart disease-related TBX5 mutations

先天性心脏病(congenital heart diseases,CHDs)严重影响人类健康,遗传因素与CHDs的发生密切相关。在辅助生育过程中,利用极体活检、卵裂球活检和囊胚活检等方法,结合单细胞DNA扩增及高通量测序技术,能够准确检测出着床前胚胎中与单基因遗传疾病相关的致病突变。T盒转录因子5(T-box transcription factor 5,TBX5)是心脏和上肢发育的重要转录因子,已报道有227种TBX5突变与CHDs相关。通过植入前单基因遗传病检测(preimplantation genetic testing for monogenic disease,PGT-M),检测胚胎中是否存在CHDs相关性TBX5突变,对于预防CHDs的发生有重要意义。本文系统整理了已报道的TBX5突变相关信息,并结合家族性遗传数据、动物模型、诱导多潜能干细胞疾病模型和预测软件,对TBX5错义突变进行了综合分析,以期为CHDs相关TBX5突变的PGT-M提供参考。

Congenital heart diseases(CHDs)seriously affect human health,and genetic mutation is closely related to the occurrence of CHDs.In the process of assisted reproduction,the use of methods such as polar body biopsy,blastomere biopsy and blastocyst biopsy,combined with single-cell DNA amplification and high-throughput sequencing technology,can accurately detect pathogenic mutations associated with single-gene genetic diseases in pre-implantation embryos.T-box transcription factor 5(TBX5)is an important transcription factor for heart and upper limb development.It is reported 227 TBX5 mutations are related to CHDs.Preimplantation genetic testing for monogenic disease(PGT-M)to detect CHD-related TBX5 mutations in embryos is of great significance for preventing the occurrence of CHDs.In this review,we systematically summarized the TBX5 mutation information,and analyzed the deleterious effects of TBX5 missense mutations based on familial genetic data,animal models,induced pluripotent stem cell disease models and prediction software to provide references for the detection of CHD-related TBX5 mutations using PGT-M.