扩张型心肌病（DCM）是导致心力衰竭的常见原因，其病因不明、发病率高、预后极差，早期诊断治疗是临床亟待解决的问题，国内外研究发现DCM与基因突变密切相关。吡咯琳-5-羧酸还原酶（P5CR）是脯氨酸合成代谢途径的关键酶，脯氨酸是心肌胶原蛋白中最丰富的氨基酸，胶原含量和结构的改变是心室重塑的主要原因。在发现DCM患者P5CR基因第五外显子缺失突变及该突变体酶活力减弱的基础上，本项目拟采用核酸测序方法筛查DCM患者白细胞P5CR基因外显子缺失分布情况，采用酶学及结构生物学方法分析P5CR突变体酶活性及其X射线晶体结构，以探索P5CR基因突变与DCM的关系。详细了解DCM患者基因外显子缺失分布情况，可为DCM的早期诊断及治疗干预提供明确的基因靶向，明确P5CR缺失突变的功能与结构有助于深入了解DCM的发病机制。

Dilated cardiomyopathy (DCM), the etiology of which remains unknown, is the common cause of heart failure. It is considered to have a high incidence and poor prognosis. Clinically, early diagnosis and treatment of DCM still leaves a lot to be desired. According to the researches at home and abroad, the occurrence of DCM is closely related with the gene mutation. Ventricular remodeling is characterized by changes in the content and structure of myocardial collagen. Pyrroline-5-carboxylate reductase  (P5CR) is the key enzyme to synthesize proline, which is the principal amino acid of myocardial collagen. Based on the fact that the exon 5 deletion mutation of P5CR was found in patients with DCM and the protease activity of P5CR mutant is lower, this study aims to explore the relationship between gene mutation and DCM. In the research,we will use the technique for sequencing nucleic acids，X-ray crystallography in combination with a variety of other biochemical techniques to explore the exon deletion mutations of P5CR in DCM, the enzyme kinetics and crystal structure of mutant P5CR. A complete acquaintance with the distribution of exon deletion in DCM patients would provide gene targeting for early diagnosis and treatment of DCM. The elucidation of function and structure of P5CR protease mutant contributes to better understand the pathogenesis of DCM.