Congenital heart disease (CHD) is the most common major congenital anomaly with an incidence of ∼1% of live births and is a significant cause of birth defect–related mortality. The genetic mechanisms underlying the development of CHD are complex and remain incompletely understood. Known genetic causes include all classes of genetic variation including chromosomal aneuploidies, copy number variants, and rare and common single-nucleotide variants, which can be either de novo or inherited. Among patients with CHD, ∼8%–12% have a chromosomal abnormality or aneuploidy, between 3% and 25% have a copy number variation, and 3%–5% have a single-gene defect in an established CHD gene with higher likelihood of identifying a genetic cause in patients with nonisolated CHD. These genetic variants disrupt or alter genes that play an important role in normal cardiac development and in some cases have pleiotropic effects on other organs. This work reviews some of the most common genetic causes of CHD as well as what is currently known about the underlying mechanisms.

中文翻译：

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人类先天性心脏病的遗传基础。

先天性心脏病（CHD）是最常见的主要先天性异常，其发病率约为活产的 1%，是与出生缺陷相关的死亡率的重要原因。CHD 发展的遗传机制很复杂，目前仍未完全了解。已知的遗传原因包括所有类型的遗传变异，包括染色体非整倍体、拷贝数变异以及罕见和常见的单核苷酸变异，这些变异可以是从头或遗传的。在 CHD 患者中，约 8%–12% 有染色体异常或非整倍体，3% 至 25% 有拷贝数变异，3%–5% 在已确定的 CHD 基因中存在单基因缺陷的可能性更高确定非孤立性冠心病患者的遗传原因。这些遗传变异破坏或改变了在正常心脏发育中起重要作用的基因，并且在某些情况下对其他器官具有多效性。这项工作回顾了 CHD 的一些最常见的遗传原因以及目前已知的潜在机制。