Department of Experimental Medicine, Faculty of Medicine and Dentistry, Sapienza University of Rome, 00161 Rome, Italy.
Department of Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy.
Int J Mol Sci. 2024 Sep 10;25(18):9787. doi: 10.3390/ijms25189787.
Hereditary cardiomyopathies (CMPs), including arrhythmogenic cardiomyopathy (ACM), dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy (HCM), represent a group of heart disorders that significantly contribute to cardiovascular morbidity and mortality and are often driven by genetic factors. Recent advances in next-generation sequencing (NGS) technology have enabled the identification of rare variants in both well-established and minor genes associated with CMPs. Nowadays, a set of core genes is included in diagnostic panels for ACM, DCM, and HCM. On the other hand, despite their lesser-known status, variants in the minor genes may contribute to disease mechanisms and influence prognosis. This review evaluates the current evidence supporting the involvement of the minor genes in CMPs, considering their potential pathogenicity and clinical significance. A comprehensive analysis of databases, such as ClinGen, ClinVar, and , along with recent literature and diagnostic guidelines provides a thorough overview of the genetic landscape of minor genes in CMPs and offers guidance in clinical practice, evaluating each case individually based on the clinical referral, and insights for future research. Given the increasing knowledge on these less understood genetic factors, future studies are essential to clearly assess their roles, ultimately leading to improved diagnostic precision and therapeutic strategies in hereditary CMPs.
遗传性心肌病（CMPs），包括心律失常性心肌病（ACM）、扩张型心肌病（DCM）和肥厚型心肌病（HCM），是一组严重影响心血管发病率和死亡率的心脏疾病，通常由遗传因素驱动。新一代测序（NGS）技术的最新进展使得人们能够鉴定出与 CMPs 相关的已确立和次要基因中的罕见变异。如今，一组核心基因被纳入 ACM、DCM 和 HCM 的诊断面板中。另一方面，尽管这些次要基因的变异知之甚少，但它们可能会影响疾病机制并影响预后。这篇综述评估了支持次要基因参与 CMPs 的现有证据，考虑了它们的潜在致病性和临床意义。对 ClinGen、ClinVar 和 等数据库的全面分析，以及最近的文献和诊断指南，提供了对 CMPs 中次要基因遗传景观的全面概述，并为临床实践提供了指导，根据临床转诊情况对每个病例进行评估，并为未来的研究提供了见解。鉴于对这些理解较少的遗传因素的了解不断增加，未来的研究对于明确评估它们的作用至关重要，最终将导致遗传性 CMPs 的诊断精度和治疗策略得到改善。
