Cuda G, Lamberti A, Perrotti N, Perticone F, Mattioli P L
Department of Experimental and Clinical Medicine, G. Salvatore Medical School.
Rev Port Cardiol. 1998 Oct;17 Suppl 2:II21-31.
The impact of molecular genetics in the diagnosis and management of various forms of heritable cardiac or vascular disorders is continuously increasing thanks to the newly available laboratory tools. Familial hypertrophic cardiomyopathy (FHC), an autosomal dominant inherited disease characterized by unexplained left ventricular hypertrophy and a wide range of clinical symptoms, is the first cardiac disorder whose genetic bases have been elucidated. Linkage analysis studies have shown a statistically significant association between the disease status and at least seven genetic loci, all coding for sarcomeric proteins, in unrelated kindreds. A major challenge for physicians is to make an accurate and early diagnosis, not only on the basis of the traditional tools (i.e. physical examination and electro-echocardiography) but also to focus on the impact of genotype on clinical manifestations of FHC. In this review we present the more recent findings on the genetic basis of FHC and analyze the genotype-phenotype correlations of this disorder, whose expression may be modulated by additional factors (modifier genes, genetic background, environmental factors) other than mutations in any of the sarcometric proteins.
由于新出现的实验室工具，分子遗传学在各种遗传性心脏或血管疾病的诊断和管理中的影响正在不断增加。家族性肥厚型心肌病（FHC）是一种常染色体显性遗传病，其特征是不明原因的左心室肥厚和广泛的临床症状，它是第一种遗传基础已被阐明的心脏疾病。连锁分析研究表明，在无关的家族中，疾病状态与至少七个基因座之间存在统计学上的显著关联，所有这些基因座均编码肌节蛋白。医生面临的一个主要挑战是不仅要基于传统工具（即体格检查和超声心动图）进行准确的早期诊断，还要关注基因型对FHC临床表现的影响。在这篇综述中，我们介绍了关于FHC遗传基础的最新发现，并分析了这种疾病的基因型-表型相关性，其表达可能受到除任何肌节蛋白突变之外的其他因素（修饰基因、遗传背景、环境因素）的调节。
