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目的 本研究拟建立中国长QT综合征(LQTS)患者KCNQ1基因突变特异的诱导多能干细胞(iPSC)模型.方法 根据临床症状及心电图表现,选取1名携带c.605-2A＞G/c.815G＞A突变的LQTS患者,收集患者及其双亲尿液,分别提取尿液上皮细胞.利用编码Sox2、Klf4、Oct4、L-Myc、Nanog,、Lin28、SV40LT的附着体质粒组合或编码Sox2、Klf4、Oct4、c-Myc的逆转录病毒组合转染患者及双亲的尿液细胞.获得iPSC后对其进行外源基因沉默检测及全能性分析.结果 获得LQTS患者特异性iPSC两株:L1C4和L1C5以及患者父亲iPSC两株L2C2和L2C14和母亲的两株Q1C3和Q1C6.这6株克隆外源基因沉默,核型正常,多能性标记物表达与人胚胎干细胞相似.此外,体外分化实验及畸胎瘤实验也证明获得细胞株的全能性.结论 成功获得携带KCNQ1-c.605-2A＞G/c.815G＞A双突变的LQTS患者iPSC株,为后续机制研究奠定了基础.“,”Objective To establish patient-specific induced pluripotent stem cell (iPSC) model of Chinese long QT syndrome(LQTS) patients with KCNQ1 mutations.Methods Based on clinical symptoms and electrocardiograms,a LQTS patient carrying KCNQ1-c.605-2A＞G/c.815G＞A was selected.The epithelial cells was collected from the urine of this patient and his parents.Episomal combination coding Sox2,Klf4,Oct4,L-Myc,Nanog,Lin28 is transfected into epithelial cells of the patient and his mother and retrovirus coding Sox2,Klf4,Oct4,c-Myc into epithelial cells of his father.After iPSC lines were obtained,the silencing of exogenous genes and their pluripotency were tested.Results Two iPSC lines L1C4 and L1C5 of the patient and 4 iPSC lines L2C2,L2C14,Q1C3 and Q1C6 of parents were obtained.In these cells,exogenous genes were all silenced and the expression of human embryonic stem cell (ESC) markers were similar to human ESC.Additionally,teratoma test and EB formation test demonstrated the totipotence of these iPSC lines.Conclusion LQTS patient-specific iPSC lines could be successfully obtained,which lay the foundation of further mechanism study.