Genetics and Disease of Ventricular Muscle
Genetics and Disease of Ventricular Muscle
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DOI：
10.1101/cshperspect.a021063
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发表时间：
2014-01-01
影响因子：
5.4
通讯作者：
Seidman, Jonathan G.
中科院分区：
文献类型：
--
作者：
Fatkin, Diane;Seidman, Christine E.;Seidman, Jonathan G.
心肌病是一种与心力衰竭、心律失常和死亡相关的异质心肌疾病。遗传变异在心肌病的发病机制中起着至关重要的作用，许多单基因突变与独特的心肌病表型有关。与这些发现同时，在大人群中进行的全基因组测序研究也有了巨大的增长，数据显示每个人体内都有广泛的基因组变异。心肌病基因和预计影响疾病突变临床表达的基因中相当大的等位基因多样性表明，需要对心肌病中的单基因突变进行更细致的解释。这些发现强调需要找到新的方法来解释遗传变异套件的功能意义，以及需要考虑全球遗传变异负担、表观遗传因素和心脏环境因素的新疾病模型。
Cardiomyopathies are a heterogeneous group of heart muscle diseases associated with heart failure, arrhythmias, and death. Genetic variation has a critical role in the pathogenesis of cardiomyopathies, and numerous single-gene mutations have been associated with distinctive cardiomyopathy phenotypes. Contemporaneously with these discoveries, there has been enormous growth of genome-wide sequencing studies in large populations, data that show extensive genomic variation within every individual. The considerable allelic diversity in cardiomyopathy genes and in genes predicted to impact clinical expression of disease mutations indicates the need for a more nuanced interpretation of single-gene mutation in cardiomyopathies. These findings highlight the need to find new ways to interpret the functional significance of suites of genetic variants, as well as the need for new disease models that take global genetic variant burdens, epigenetic factors, and cardiac environmental factors into account.