Centro de Química Estrutural, Instituto Superior Técnico, Technical University of Lisbon, Lisbon, Portugal.
BMC Med Genet. 2012 Mar 19;13:17. doi: 10.1186/1471-2350-13-17.
Hypertrophic Cardiomyopathy (HCM) is a complex myocardial disorder with a recognized genetic heterogeneity. The elevated number of genes and mutations involved in HCM limits a gene-based diagnosis that should be considered of most importance for basic research and clinical medicine.
In this report, we evaluated High Resolution Melting (HRM) robustness, regarding HCM genetic testing, by means of analyzing 28 HCM-associated genes, including the most frequent 4 HCM-associated sarcomere genes, as well as 24 genes with lower reported HCM-phenotype association. We analyzed 80 Portuguese individuals with clinical phenotype of HCM allowing simultaneously a better characterization of this disease in the Portuguese population.
HRM technology allowed us to identify 60 mutated alleles in 72 HCM patients: 49 missense mutations, 3 nonsense mutations, one 1-bp deletion, one 5-bp deletion, one in frame 3-bp deletion, one insertion/deletion, 3 splice mutations, one 5'UTR mutation in MYH7, MYBPC3, TNNT2, TNNI3, CSRP3, MYH6 and MYL2 genes. Significantly 22 are novel gene mutations.
HRM was proven to be a technique with high sensitivity and a low false positive ratio allowing a rapid, innovative and low cost genotyping of HCM. In a short return, HRM as a gene scanning technique could be a cost-effective gene-based diagnosis for an accurate HCM genetic diagnosis and hopefully providing new insights into genotype/phenotype correlations.
肥厚型心肌病（HCM）是一种复杂的心肌疾病，具有公认的遗传异质性。涉及 HCM 的基因数量众多且存在突变，这限制了基于基因的诊断，而基因诊断对于基础研究和临床医学来说应该是最重要的。
在本报告中，我们通过分析 28 个与 HCM 相关的基因，包括最常见的 4 个与 HCM 相关的肌节基因，以及 24 个报告与 HCM 表型关联较低的基因，评估了高分辨率熔解（HRM）在 HCM 遗传检测中的稳健性。我们分析了 80 名葡萄牙个体，这些个体具有 HCM 的临床表型，这使得我们能够更好地描述葡萄牙人群中这种疾病的特征。
HRM 技术使我们能够在 72 名 HCM 患者中鉴定出 60 个突变等位基因：49 个错义突变，3 个无义突变，1 个 1-bp 缺失，1 个 5-bp 缺失，1 个框内 3-bp 缺失，1 个插入/缺失，3 个剪接突变，1 个 5'UTR 突变在 MYH7、MYBPC3、TNNT2、TNNI3、CSRP3、MYH6 和 MYL2 基因中。其中有 22 个是新的基因突变。
HRM 被证明是一种具有高灵敏度和低假阳性率的技术，可快速、创新、低成本地对 HCM 进行基因分型。在短时间内，HRM 作为一种基因扫描技术，可以为准确的 HCM 遗传诊断提供一种具有成本效益的基于基因的诊断方法，并有望为基因型/表型相关性提供新的见解。
