Among inherited cardiac conditions, a special place is kept by cardiomyopathies (CMPs) and channelopathies (CNPs), which pose a substantial healthcare burden due to the complexity of the therapeutic management and cause early mortality. Like other inherited cardiac conditions, genetic CMPs and CNPs exhibit incomplete penetrance and variable expressivity even within carriers of the same pathogenic deoxyribonucleic acid variant, challenging our understanding of the underlying pathogenic mechanisms. Until recently, the lack of accurate physiological preclinical models hindered the investigation of fundamental cellular and molecular mechanisms. The advent of induced pluripotent stem cell (iPSC) technology, along with advances in gene editing, offered unprecedented opportunities to explore hereditary CMPs and CNPs. Hallmark features of iPSCs include the ability to differentiate into unlimited numbers of cells from any of the three germ layers, genetic identity with the subject from whom they were derived, and ease of gene editing, all of which were used to generate "disease-in-a-dish" models of monogenic cardiac conditions. Functionally, iPSC-derived cardiomyocytes that faithfully recapitulate the patient-specific phenotype, allowed the study of disease mechanisms in an individual-/allele-specific manner, as well as the customization of therapeutic regimen. This review provides a synopsis of the most important iPSC-based models of CMPs and CNPs and the potential use for modeling disease mechanisms, personalized therapy and deoxyribonucleic acid variant functional annotation.

中文翻译：

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患者特异性诱导的多能干细胞，作为遗传性心肌病和通道病的“一碟式疾病”模型-长达15年的研究。

在遗传性心脏病中，心肌病（CMPs）和通道病（CNPs）占据了特殊的位置，由于治疗管理的复杂性并造成早期死亡，它们构成了巨大的医疗负担。像其他遗传性心脏病一样，遗传CMP和CNP即使在相同病原脱氧核糖核酸变异体的携带者中也表现出不完全的渗透性和可变的表达能力，这挑战了我们对潜在病原机制的理解。直到最近，缺乏精确的生理学临床前模型仍阻碍了对基本细胞和分子机制的研究。诱导多能干细胞（iPSC）技术的出现，以及基因编辑的进步，为探索遗传性CMP和CNP提供了前所未有的机会。iPSC的标志性特征包括能够从三个细菌层的任何一个分化为无限数量的细胞，与它们起源的受试者具有遗传同一性以及易于进行基因编辑的能力，所有这些都被用来产生“疾病”。单基因心脏疾病的“一个菜”模型。从功能上讲，iPSC衍生的心肌细胞忠实地概括了患者特异性表型，从而允许以个体/等位基因特异性方式研究疾病机制，以及定制治疗方案。这项审查提供了最重要的基于CMP和CNP的基于iPSC的模型的提要，以及为疾病机理，个性化治疗和脱氧核糖核酸变异功能注释建模的潜在用途。