特发性心房颤动致病基因PRRX1新突变的发现及功能分析  

Identification and functional analysis of a new mutation in the PRRX1 gene responsible for idiopathic atrial fibrillation

作　　者：李宁 仇兴标[2] 徐迎佳 杨奕清 刘宗军[1] LI Ning;Qiu Xingbiao;XU Yingjia;YANG Yiqing;LIU Zongjun(Department of Cardiology,Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200062;Department of Cardiology,Shanghai Chest Hospital,Shanghai Jiao Tong University,Shanghai 200030;Department of Cardiology and Cardiovascular Research Laboratory,Shanghai Fifth People′s Hospital,Fudan University,Shanghai 200240,China)

机构地区：[1]上海中医药大学附属普陀医院心内科,200062 [2]上海交通大学附属胸科医院心内科,200030 [3]复旦大学附属上海市第五人民医院心内科,心血管研究室,200240

出　　处：《国际心血管病杂志》2022年第3期176-180,共5页International Journal of Cardiovascular Disease

基　　金：国家自然科学基金(81470372)。

摘　　要：目的:探索特发性心房颤动(房颤)致病基因PRRX1新突变并分析其功能。方法:收集192例特发性房颤患者和212名健康者的外周静脉血标本,提取基因组DNA,测序分析PRRX1基因以发现致房颤突变。克隆PRRX1基因,构建其野生型表达载体,通过定位诱变获得突变体,转染Hela细胞,通过双荧光报告基因分析其功能特性。结果:在其中1例特发性房颤患者发现PRRX1基因新突变,即NM_022716.4:c.425T>C;p.(Phe142Ser)突变。该突变不存在于212名志愿者,也不存在于其余191例房颤患者中。功能分析显示突变型PRRX1对靶基因SHOX2的转录激活作用显著降低。结论:发现房颤致病基因PRRX1新的功能丧失性突变,对房颤的精准预防具有潜在的临床意义。Objective:To explore novel mutations in the causative gene PRRX1 in idiopathic atrial fibrillation(AF)and analyze its function.Methods:Peripheral venous blood samples were collected from 192 unrelated patients suffering from idiopathic AF and 212 unrelated healthy volunteers employed as control group.Genomic DNA was extracted from the blood leucocytes of each group.Sequencing analysis of the PRRX1 gene was conducted to explore an AF-based mutation.The PRRX1 gene was cloned with its wild-type expression vector was constructed.The mutant-type PRRX1 expression vector was obtained via sitedirected mutagenesis.Hela cells were transiently transfected,and the functional characteristics of the mutant-type PRRX1 were assayed with dual-luciferase reporters.Results:A new PRRX1 mutation,NM_022716.4:c.425T>C;p.(Phe142Ser),was discovered in a patient suffering from idiopathic AF,which was not observed in the 212 unrelated healthy volunteers or in the other 191 AF patients.The results of functional analysis demonstrated that the mutation significantly decreased the ability of PRRX1 to transactivate the expression of SHOX2(a target gene of PRRX1).Conclusion:A new loss-of-function of AF-based mutation in the PRRX1 gene has potential clinical significance for precise prevention of AF.

关 键 词：心房颤动 医学遗传学 转录调节 PRRX1基因 报告基因分析 

分 类 号：R541.75[医药卫生—心血管疾病]