Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Int J Mol Sci. 2024 Oct 25;25(21):11460. doi: 10.3390/ijms252111460.
Dilated cardiomyopathy (DCM) is characterized by reduced systolic function and cardiac dilation. Cases without an identified secondary cause are classified as idiopathic dilated cardiomyopathy (IDC). Over the last 35 years, many cases of IDC have increasingly been recognized to be genetic in etiology with a core set of definitively causal genes in up to 40% of cases. While over 200 genes have been associated with DCM, the evidence supporting pathogenicity for most remains limited. Further, rapid advances in sequencing and bioinformatics have recently revealed a complex genetic spectrum ranging from monogenic to polygenic in DCM. These advances have also led to the discovery of causal and modifier genetic variants in secondary forms of DCM (e.g., alcohol-induced cardiomyopathy). Current guidelines recommend genetic counseling and screening, as well as endorsing a handful of genotype-specific therapies (e.g., device placement in cardiomyopathy). The future of genetics in DCM will likely involve polygenic risk scores, direct-to-consumer testing, and pharmacogenetics, requiring providers to have a thorough understanding of this rapidly developing field. Herein we outline three decades of genetics in DCM, summarize recent advances, and project possible future avenues for the field.
扩张型心肌病（DCM）的特征是收缩功能降低和心脏扩张。没有明确继发原因的病例被归类为特发性扩张型心肌病（IDC）。在过去的 35 年中，越来越多的 IDC 病例被认为是病因学上的遗传，多达 40%的病例有明确的致病基因核心集。尽管已经有 200 多个基因与 DCM 相关，但大多数基因的致病性证据仍然有限。此外，测序和生物信息学的快速发展最近揭示了 DCM 中从单基因到多基因的复杂遗传谱。这些进展还导致发现了继发性 DCM（例如，酒精性心肌病）的因果和修饰基因变异。目前的指南建议进行遗传咨询和筛查，并支持少数几种针对特定基因型的治疗方法（例如，心脏起搏器植入治疗心肌病）。DCM 遗传学的未来可能涉及多基因风险评分、直接面向消费者的检测和药物遗传学，这要求提供者对这个快速发展的领域有一个全面的了解。本文概述了 DCM 三十年来的遗传学研究进展，总结了最近的进展，并预测了该领域未来可能的发展方向。
