Identifying sarcomere gene mutations in hypertrophic cardiomyopathy: a personal history.
Identifying sarcomere gene mutations in hypertrophic cardiomyopathy: a personal history.
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DOI：
10.1161/circresaha.110.223834
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发表时间：
2011-03-18
影响因子：
20.1
通讯作者：
Seidman JG
中科院分区：
文献类型：
--
作者：
Seidman CE;Seidman JG
这篇文章提供了一个历史和个人的角度对肥厚型心肌病（HCM）的遗传原因的发现。最初详细描述了该疾病的显着和各种表现的医生的非凡见解，具有临床诊断和分子遗传学技能的多学科团队之间的合作，以及数十名学员的辛勤工作，解决了HCM的病因之谜，并意外地证明了肌节蛋白基因突变是疾病的原因。除了庆祝HCM遗传研究20周年外，本文还作为主题综述系列的介绍性概述，将介绍肥厚性心脏病领域的当代进展。通过遗传学方法的进步的持续应用，结合对人类突变后果的生物化学和生物物理分析，已经出现了关于HCM和肌节生物学的基础知识。扩大研究以阐明收缩蛋白中的微妙遗传变异重塑人类心脏的机制仍然是一个令人兴奋的机会，这一机会有相当大的希望提供限制甚至预防HCM发病机制的新策略。
This article provides an historical and personal perspective on the discovery of genetic causes for hypertrophic cardiomyopathy (HCM). Extraordinary insights of physicians who initially detailed remarkable and varied manifestations of the disorder, collaboration among multidisciplinary teams with skills in clinical diagnostics and molecular genetics, and hard work by scores of trainees, solved the etiologic riddle of HCM, and unexpectedly demonstrated mutations in sarcomere protein genes as the cause of disease. In addition to celebrating 20 years of genetic research in HCM, this article serves as an introductory overview to a thematic review series that will present contemporary advances in the field of hypertrophic heart disease. Through the continued application of advances in genetic methodologies, combined with biochemical and biophysical analyses of the consequences of human mutations, fundamental knowledge about HCM and sarcomere biology has emerged. Expanding research to elucidate the mechanisms by which subtle genetic variation in contractile proteins remodel the human heart remains an exciting opportunity, one with considerable promise to provide new strategies to limit or even prevent HCM pathogenesis.