Yigit Gökhan, Wollnik Bernd
Institute of Human Genetics, University Medical Center Göttingen, Heinrich-Düker-Weg 12, 37073 Göttingen, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Göttingen, Göttingen, Germany.
Med Genet. 2021 Dec 3;33(3):235-243. doi: 10.1515/medgen-2021-2094. eCollection 2021 Sep.
Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous cardiac disease that is mainly characterized by left ventricular hypertrophy in the absence of any additional cardiac or systemic disease. HCM is genetically heterogeneous, inherited mainly in an autosomal dominant pattern, and so far pathogenic variants have been identified in more than 20 genes, mostly encoding proteins of the cardiac sarcomere. Based on its variable penetrance and expressivity, pathogenicity of newly identified variants often remains unsolved, underlining the importance of cellular and tissue-based models that help to uncover causative genetic alterations and, additionally, provide appropriate systems for the analysis of disease hallmarks as well as for the design and application of new therapeutic strategies like drug screenings and genome/base editing approaches. Here, we review the current state of cellular and tissue-engineered models and provide future perspectives for personalized therapeutic strategies of HCM.
肥厚型心肌病（HCM）是一种临床异质性心脏疾病，主要特征为在无任何其他心脏或全身性疾病的情况下出现左心室肥厚。HCM具有遗传异质性，主要以常染色体显性模式遗传，迄今为止已在20多个基因中鉴定出致病变异，这些基因大多编码心肌肌节蛋白。基于其可变的外显率和表达性，新鉴定变异的致病性往往难以确定，这凸显了基于细胞和组织的模型的重要性，这些模型有助于揭示致病基因改变，此外，还能为疾病特征分析以及药物筛选和基因组/碱基编辑方法等新治疗策略的设计与应用提供合适的系统。在此，我们综述了细胞和组织工程模型的现状，并为HCM的个性化治疗策略提供未来展望。
