My Ilaria, Di Pasquale Elisa
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy.
Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, Italy.
J Clin Med. 2021 Mar 9;10(5):1149. doi: 10.3390/jcm10051149.
Genetic cardiomyopathies represent a wide spectrum of inherited diseases and constitute an important cause of morbidity and mortality among young people, which can manifest with heart failure, arrhythmias, and/or sudden cardiac death. Multiple underlying genetic variants and molecular pathways have been discovered in recent years; however, assessing the pathogenicity of new variants often needs in-depth characterization in order to ascertain a causal role in the disease. The application of human induced pluripotent stem cells has greatly helped to advance our knowledge in this field and enabled to obtain numerous in vitro patient-specific cellular models useful to study the underlying molecular mechanisms and test new therapeutic strategies. A milestone in the research of genetically determined heart disease was the introduction of genomic technologies that provided unparalleled opportunities to explore the genetic architecture of cardiomyopathies, thanks to the generation of isogenic pairs. The aim of this review is to provide an overview of the main research that helped elucidate the pathophysiology of the most common genetic cardiomyopathies: hypertrophic, dilated, arrhythmogenic, and left ventricular noncompaction cardiomyopathies. A special focus is provided on the application of gene-editing techniques in understanding key disease characteristics and on the therapeutic approaches that have been tested.
遗传性心肌病是一类广泛的遗传性疾病，是年轻人发病和死亡的重要原因，可表现为心力衰竭、心律失常和/或心源性猝死。近年来发现了多种潜在的基因变异和分子途径；然而，评估新变异的致病性通常需要深入表征，以确定其在疾病中的因果作用。人类诱导多能干细胞的应用极大地推动了我们在这一领域的认识，并使我们能够获得大量体外患者特异性细胞模型，有助于研究潜在的分子机制并测试新的治疗策略。基因决定的心脏病研究中的一个里程碑是基因组技术的引入，由于同基因对的产生，基因组技术为探索心肌病的遗传结构提供了无与伦比的机会。本综述的目的是概述有助于阐明最常见遗传性心肌病（肥厚型、扩张型、致心律失常型和左心室致密化不全心肌病）病理生理学的主要研究。特别关注基因编辑技术在理解关键疾病特征方面的应用以及已测试的治疗方法。
