Cai Dihui, Zheng Zequn, Jin Xiaojun, Fu Yin, Cen Lichao, Ye Jiachun, Song Yongfei, Lian Jiangfang
Department of Cardiovascular, Lihuili Hospital Affiliated to Ningbo University, Ningbo University, Zhejiang Province, Ningbo, China.
Department of Cardiovascular, First Affiliated Hospital of Shantou University Medical College, Shantou, China.
J Cardiovasc Transl Res. 2023 Feb;16(1):209-220. doi: 10.1007/s12265-022-10298-x. Epub 2022 Aug 17.
Type 2 long QT syndrome (LQT2) is the second most common subtype of long QT syndrome and is caused by mutations in KCHN2 encoding the rapidly activating delayed rectifier potassium channel vital for ventricular repolarization. Sudden cardiac death is a sentinel event of LQT2. Preclinical diagnosis by genetic testing is potentially life-saving.Traditional LQT2 models cannot wholly recapitulate genetic and phenotypic features; therefore, there is a demand for a reliable experimental model. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) meet this challenge. This review introduces the advantages of the hiPSC-CM model over the traditional model and discusses how hiPSC-CM and gene editing are used to decipher mechanisms of LQT2, screen for cardiotoxicity, and identify therapeutic strategies, thus promoting the realization of precision medicine for LQT2 patients.
2型长QT综合征（LQT2）是长QT综合征的第二常见亚型，由编码对心室复极至关重要的快速激活延迟整流钾通道的KCHN2基因突变引起。心源性猝死是LQT2的标志性事件。通过基因检测进行临床前诊断可能挽救生命。传统的LQT2模型不能完全概括遗传和表型特征；因此，需要一种可靠的实验模型。人诱导多能干细胞衍生的心肌细胞（hiPSC-CMs）应对了这一挑战。本文综述介绍了hiPSC-CM模型相对于传统模型的优势，并讨论了如何利用hiPSC-CM和基因编辑来解读LQT2的机制、筛选心脏毒性以及确定治疗策略，从而推动LQT2患者精准医学的实现。
