Edwards Jonathan J, Gelb Bruce D
aThe Mindich Child Health and Development Institute bDepartment of Pediatrics, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Curr Opin Cardiol. 2016 May;31(3):235-41. doi: 10.1097/HCO.0000000000000274.
The goal of this review is to highlight recent discoveries in the field of genetics as it relates to congenital heart disease (CHD). Recent advancements in next generation sequencing technology and tools to interpret this growing body of data have allowed us to refine our understanding of the molecular mechanisms that result in CHD.
From multiple different study designs, the genetic lesions that cause CHD are increasingly being elucidated. Of the more novel findings, a forward genetic screen in mice has implicated recessive inheritance and the ciliome broadly in CHD pathogenesis. The developmental delays frequently observed in patients with CHD appear to result from mutations affecting genes that overlap heart and brain developmental regulation. A meta-analysis has provided clarity, discriminating pathologic from incidental copy number variations and defining a critical region or gene.
Recent technological advances have rapidly expanded our understanding of CHD genetics, and support the applicability to the clinical domain in both sporadic and inherited disease. Though significant gaps remain, genetic lesions remain the primary explanation for CHD pathogenesis, although the precise mechanism is likely multifactorial.
本综述的目的是强调遗传学领域与先天性心脏病（CHD）相关的最新发现。下一代测序技术以及解读这一不断增长的数据量的工具的最新进展，使我们能够深化对导致CHD的分子机制的理解。
通过多种不同的研究设计，导致CHD的遗传损伤正越来越多地被阐明。在更新颖的发现中，小鼠正向遗传学筛选表明隐性遗传和纤毛组在CHD发病机制中广泛涉及。CHD患者中经常观察到的发育延迟似乎是由影响心脏和大脑发育调控重叠基因的突变所致。一项荟萃分析提供了清晰的结果，区分了病理性与偶然性拷贝数变异，并确定了关键区域或基因。
最近的技术进步迅速扩展了我们对CHD遗传学的理解，并支持其在散发性和遗传性疾病临床领域的应用。尽管仍存在重大差距，但遗传损伤仍是CHD发病机制的主要解释，尽管确切机制可能是多因素的。
