Sepp R, Csanády M
II. Belgyógyászati Klinika, Szent-Györgyi Albert Orvostudományi Egyetem, Szeged.
Orv Hetil. 1998 Aug 16;139(33):1965-71.
Recent developments in molecular genetics have allowed to identify mutations in seven genes coding the beta myosin heavy chain, troponin T, alpha tropomyosin, myosin binding protein C, essential and regulatory myosin light chains and troponin I causing hypertrophic cardiomyopathy. These mutations affect critical, evolutionary conserved nucleotides of these genes and influence vital functions of the encoded proteins. As all seven genes encodes sarcomeric proteins in the heart muscle, hypertrophic cardiomyopathy is regarded these days as a disease of the sarcomer. Recent data indicate that some mutations are associated with "malignant" clinical picture, with rapidly developing, severe symptoms of the disease and increased risk of sudden cardiac death while other mutations bear a more favourable prognosis. Apart of the disease causing mutation other factors, including disease modifier genes, are likely to make an impact on the clinical appearance of hypertrophic cardiomyopathy. The knowledge provided by molecular genetics influences the clinical management of the disease even today and based on the investigation of mutation carrying patients new diagnostic criteria was proposed for hypertrophic cardiomyopathy. The challenge for the future is the establishment of routine genetic diagnostics and the development of possible gene therapy.
分子遗传学的最新进展已能够鉴定出七个基因中的突变，这些基因编码β-肌球蛋白重链、肌钙蛋白T、原肌球蛋白α、肌球蛋白结合蛋白C、必需和调节性肌球蛋白轻链以及肌钙蛋白I，这些突变会导致肥厚型心肌病。这些突变影响这些基因中关键的、进化保守的核苷酸，并影响所编码蛋白质的重要功能。由于所有这七个基因都编码心肌中的肌节蛋白，如今肥厚型心肌病被视为一种肌节疾病。最近的数据表明，一些突变与“恶性”临床表现相关，伴有疾病快速发展、严重症状以及心脏性猝死风险增加，而其他突变的预后则较为良好。除了致病突变外，其他因素，包括疾病修饰基因，可能会对肥厚型心肌病的临床表现产生影响。即使在今天，分子遗传学提供的知识也影响着该疾病的临床管理，并且基于对携带突变患者的研究，提出了肥厚型心肌病的新诊断标准。未来的挑战是建立常规基因诊断以及开发可能的基因疗法。
