Okata Shinichiro, Yuasa Shinsuke, Yamane Teiichi, Furukawa Tetsushi, Fukuda Keiichi
Department of Cardiology, Keio University School of Medicine, Japan.
J Med Dent Sci. 2013 Mar 1;60(1):17-22.
The long QT syndrome type 2 (LQT2) is inheritable life threatening arrhythmic disorder and one of the most common genetic variants in long QT syndrome. There are some indications for treatment of the patients with LQT2 but it is impossible to completely prevent fatal arrhythmia. To develop novel therapy for the patients with LQT2, it has been desired to generate diseasespecific and patient-specific disease model. Human induced pluripotent stem (iPS) cells are somatic cell-derived pluripotent stem cells with infinite proliferation ability and multipotency. Patient-specific iPS cells can be derived from patient somatic cells, have all genomic information encoded in patient's genome including mutation and all SNPs, and can be ideal disease models of the patients. To generate disease model for LQT2 by iPS cells, we should firstly generate iPS cells from the patient with LQT2 and confirm the genomic mutation in iPS cells. In this study, we showed the successful generation of iPS cells from a patient with KCNH2 G603D mutation. The patient specific iPS cells properly expressed stem cell markers, such as NANOG and OCT3/4. We also confirmed that the KCNH2 G603D (G1808A) mutation was taken over in patient specific iPS cells. These patient-specific iPS cells may contribute to the future analysis for disease pathogenesis and drug innovation.
2型长QT综合征（LQT2）是一种可遗传的危及生命的心律失常疾病，也是长QT综合征中最常见的遗传变异之一。对于LQT2患者有一些治疗指征，但完全预防致命性心律失常是不可能的。为了开发针对LQT2患者的新疗法，人们一直期望生成疾病特异性和患者特异性的疾病模型。人诱导多能干细胞（iPS细胞）是源自体细胞的多能干细胞，具有无限增殖能力和多能性。患者特异性iPS细胞可以从患者体细胞中获得，包含患者基因组中编码的所有基因组信息，包括突变和所有单核苷酸多态性（SNP），并且可以成为患者理想的疾病模型。要通过iPS细胞生成LQT2疾病模型，我们首先应该从LQT2患者中生成iPS细胞，并确认iPS细胞中的基因突变。在本研究中，我们展示了成功从一名携带KCNH2 G603D突变的患者中生成iPS细胞。患者特异性iPS细胞正确表达了干细胞标志物，如NANOG和OCT3/4。我们还确认KCNH2 G603D（G1808A）突变在患者特异性iPS细胞中得以保留。这些患者特异性iPS细胞可能有助于未来对疾病发病机制的分析和药物创新。
