By using a nonintegrating plasmid delivery system, we generated induced pluripotent stem cells (iPSCs) from the urine cells of a male patient from the family carrying the TMC1 p.M418K mutation. This mutation is homologous to that in Beethoven mice, which were treated by gene editing successfully. The resulting iPSCs had a normal karyotype, showed pluripotency by immunofluorescence staining, and differentiated into the three germ layers in vivo. This cellular model will provide a useful platform for investigating the pathogenic mechanisms of TMC1-related deafness, further laying the foundation for clinical transformation applications and providing a reference for the final gene therapy in humans.

通过使用非整合质粒递送系统，我们从一名携带TMC1 p.M418K 突变家族的男性患者的尿细胞中生成了诱导多能干细胞 (iPSC) 。这种突变与通过基因编辑成功治疗的贝多芬小鼠中的突变是同源的。由此产生的iPSCs具有正常的核型，通过免疫荧光染色显示出多能性，并在体内分化成三个胚层。该细胞模型将为研究TMC1相关性耳聋的发病机制提供一个有用的平台，进一步为临床转化应用奠定基础，并为人类最终的基因治疗提供参考。