Chinese University of Hong Kong, Hong Kong SAR, China.
Kunming Institute of Zoology-Chinese University of Hong Kong (KIZ-CUHK) Joint Laboratory of Bioresources and Molecular Research of Common Diseases, Hong Kong SAR, China.
Zool Res. 2023 May 18;44(3):577-590. doi: 10.24272/j.issn.2095-8137.2022.463.
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 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（CHD）在活产儿中的发病率高达 1%，是导致先天性缺陷死亡的主要原因之一。虽然已有数百个基因被认为与 CHD 的遗传病因有关，但它们在 CHD 发病机制中的作用仍知之甚少。这在很大程度上反映了 CHD 的散发性，以及其表现度和不完全外显率的可变性。我们回顾了 CHD 的单基因病因和寡基因病因的证据，以及突变、常见变体和遗传修饰因子的作用。为了进一步深入了解发病机制，我们利用跨物种的单细胞数据，研究了在发育中的人类和小鼠胚胎心脏中与 CHD 相关的基因的细胞表达特征。了解 CHD 的遗传病因可能使精准医学和产前诊断得以应用，从而促进早期干预，改善 CHD 患者的预后。
