Roma-Rodrigues Catarina, Fernandes Alexandra R
UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, Campus de Caparica, Caparica, Portugal.
UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, Campus de Caparica, Caparica, Portugal ; Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
Appl Clin Genet. 2014 Oct 3;7:195-208. doi: 10.2147/TACG.S49126. eCollection 2014.
Hypertrophic cardiomyopathy (HCM) is a primary disease of the cardiac muscle that occurs mainly due to mutations (>1,400 variants) in genes encoding for the cardiac sarcomere. HCM, the most common familial form of cardiomyopathy, affecting one in every 500 people in the general population, is typically inherited in an autosomal dominant pattern, and presents variable expressivity and age-related penetrance. Due to the morphological and pathological heterogeneity of the disease, the appearance and progression of symptoms is not straightforward. Most HCM patients are asymptomatic, but up to 25% develop significant symptoms, including chest pain and sudden cardiac death. Sudden cardiac death is a dramatic event, since it occurs without warning and mainly in younger people, including trained athletes. Molecular diagnosis of HCM is of the outmost importance, since it may allow detection of subjects carrying mutations on HCM-associated genes before development of clinical symptoms of HCM. However, due to the genetic heterogeneity of HCM, molecular diagnosis is difficult. Currently, there are mainly four techniques used for molecular diagnosis of HCM, including Sanger sequencing, high resolution melting, mutation detection using DNA arrays, and next-generation sequencing techniques. Application of these methods has proven successful for identification of mutations on HCM-related genes. This review summarizes the features of these technologies, highlighting their strengths and weaknesses. Furthermore, current therapeutics for HCM patients are correlated with clinically observed phenotypes and are based on the alleviation of symptoms. This is mainly due to insufficient knowledge on the mechanisms involved in the onset of HCM. Tissue engineering alongside regenerative medicine coupled with nanotherapeutics may allow fulfillment of those gaps, together with screening of novel therapeutic drugs and target delivery systems.
肥厚型心肌病（HCM）是一种主要由编码心肌肌节的基因突变（>1400种变异）引起的原发性心肌疾病。HCM是心肌病最常见的家族形式，在普通人群中每500人就有1人受影响，通常以常染色体显性模式遗传，表现出可变的表达性和与年龄相关的外显率。由于该疾病在形态学和病理学上的异质性，症状的出现和进展并不简单。大多数HCM患者无症状，但高达25%的患者会出现严重症状，包括胸痛和心源性猝死。心源性猝死是一个戏剧性事件，因为它毫无征兆地发生，且主要发生在年轻人身上，包括受过训练的运动员。HCM的分子诊断至关重要，因为它可以在HCM临床症状出现之前检测出携带HCM相关基因突变的个体。然而，由于HCM的基因异质性，分子诊断很困难。目前，主要有四种技术用于HCM的分子诊断，包括桑格测序、高分辨率熔解、使用DNA阵列的突变检测和下一代测序技术。这些方法的应用已被证明在识别HCM相关基因突变方面是成功的。本综述总结了这些技术的特点，突出了它们的优缺点。此外，目前针对HCM患者的治疗方法与临床观察到的表型相关，并且基于症状的缓解。这主要是由于对HCM发病机制的了解不足。组织工程与再生医学以及纳米治疗相结合，可能填补这些空白，同时筛选新型治疗药物和靶向递送系统。
