Chumakova Olga S, Baulina Natalia M
Laboratory of Functional Genomics of Cardiovascular Diseases, National Medical Research Centre of Cardiology Named After E.I. Chazov, Moscow, Russia.
Front Cardiovasc Med. 2023 Jul 31;10:1236539. doi: 10.3389/fcvm.2023.1236539. eCollection 2023.
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease associated with morbidity and mortality at any age. As studies in recent decades have shown, the genetic architecture of HCM is quite complex both in the entire population and in each patient. In the rapidly advancing era of gene therapy, we have to provide a detailed molecular diagnosis to our patients to give them the chance for better and more personalized treatment. In addition to emphasizing the importance of genetic testing in routine practice, this review aims to discuss the possibility to go a step further and create an expanded genetic panel that contains not only variants in core genes but also new candidate genes, including those located in deep intron regions, as well as structural variations. It also highlights the benefits of calculating polygenic risk scores based on a combination of rare and common genetic variants for each patient and of using non-genetic HCM markers, such as microRNAs that can enhance stratification of risk for HCM in unselected populations alongside rare genetic variants and clinical factors. While this review is focusing on HCM, the discussed issues are relevant to other cardiomyopathies.
肥厚型心肌病（HCM）是最常见的遗传性心脏病，在任何年龄都与发病率和死亡率相关。近几十年来的研究表明，HCM的遗传结构在整个人群和每个患者中都相当复杂。在基因治疗迅速发展的时代，我们必须为患者提供详细的分子诊断，以便为他们提供更好、更个性化治疗的机会。除了强调基因检测在常规实践中的重要性外，本综述旨在探讨进一步拓展的可能性，创建一个扩展的基因检测组合，其中不仅包含核心基因的变异，还包括新的候选基因，包括位于内含子深处区域的基因以及结构变异。它还强调了基于每个患者的罕见和常见基因变异组合计算多基因风险评分以及使用非基因HCM标志物（如微小RNA）的益处，这些微小RNA可以在未选择的人群中与罕见基因变异和临床因素一起增强HCM风险分层。虽然本综述聚焦于HCM，但所讨论的问题与其他心肌病相关。
