扩张型心肌病（DCM）是一类既有遗传又有非遗传原因造成的心肌病，新近发现其发病率高于1/2500，不仅是导致心力衰竭的重要病因，而且是导致心脏移植的首要原因。DCM可导致进行性心力衰竭和猝死，5年病死率高达50%，且尚无有效的根本性治疗措施。我们的前期研究通过对500名DCM患者进行83个致病基因或候选基因的高通量测序和数据分析，发现TTN是对DCM遗传学病因最大的贡献基因，并建立了相应的TTN截短突变knock in大鼠模型。并且采用芯片技术筛查出了一系列差异性表达的miRNAs和lncRNA，获得了一类在DCM心力衰竭中差异性表达的miRNAs和lncRNA表达谱。在本项目中我们将从遗传的角度出发，深入的研究以TTN为代表的致病基因突变对DCM发病的影响及作用机制，及以非编码RNA为代表的表观遗传学影响因素对DCM发病的作用及机制。进而，我们将采用基因编辑技术对DCM进行基因治疗。

Dilated cardiomyopathy (DCM) is a kind of cardiomyopathy with both genetic and non genetic causes. It is newly discovered that the incidence rate is higher than 1/2500. Moreover, it is not only an important cause of heart failure, but also a leading cause of heart transplantation. DCM can lead to progressive heart failure and sudden death, the 5 year mortality rate is up to 50%, and up to now there is no effective treatment. In our previous study, high-throughput sequencing and data analysis of 83 genes or candidate genes from 500 patients with DCM were performed. We found that TTN was the greatest genetic cause of DCM, and we established the corresponding TTN truncating mutation knock in rat models. Moreocer, a series of differentially expressed miRNAs and lncRNA were screened out, and the profile of miRNAs and lncRNA biomarker in DCM heart failure was obtained. In the current project, we will conduct in-depth study from a genetic point of view, to investigate the pathogenic gene mutation effects and mechanisms in DCM and the effects and mechanisms of non-coding RNA. In addition, we will use gene editing technology to perform gene therapy of DCM.