Congenital heart disease (CHD) is observed in up to 1% of live births and is one of the leading causes of mortality from birth defects. While hundreds of genes have been implicated in the genetic etiology of CHD, their role in CHD pathogenesis is still poorly understood. This is largely a reflection of the sporadic nature of CHD, as well as its variable expressivity and incomplete penetrance. We reviewed the monogenic causes and evidence for oligogenic etiology of CHD, as well as the role of de novo mutations, common variants, and genetic modifiers. For further mechanistic insight, we leveraged single-cell data across species to investigate the cellular expression characteristics of genes implicated in CHD in developing human and mouse embryonic hearts. Understanding the genetic etiology of CHD may enable the application of precision medicine and prenatal diagnosis, thereby facilitating early intervention to improve outcomes for patients with CHD.
先天性心脏病是出生缺陷致死的主要原因之一，发病率约占新生儿的1%。虽然数百个基因鉴定出来与先天性心脏病遗传有关，但是先天性心脏病的遗传病因及发病机制仍知之甚少。这主要是由于先天性心脏病的可变的表现度和不完全外显造成的。该综述回顾了先天性心脏病的单基因遗传及寡基因遗传的证据，及新生突变，常见突变和遗传修饰因子的作用。为了进一步了解致病机制，我们使用跨物种的单细胞测序数据来揭示先天性心脏病基因在人类和小鼠胚胎心脏中的细胞表达特征。深入了解 CHD 的遗传病因可能有助于实施精准医学和产前诊断，从而促进早期干预以改善 CHD 患者的预后。.
Keywords: Common copy number variant; Congenital heart disease; De novo mutation; Genetic modifier; Protective variant; Single cell sequencing.