Although congenital heart disease (CHD) is the most common survivable birth defect, the etiology of most CHD remains unclear. Several lines of evidence from humans and vertebrate models have supported a genetic component for CHD, yet the extreme locus heterogeneity and lack of a distinct genotype-phenotype correlation have limited causative gene discovery. However, recent advances in genomic technologies are permitting detailed evaluation of the genetic abnormalities in large cohorts of CHD patients. This has led to the identification of copy-number variation and de novo mutations together accounting for up to 15% of CHD. Further, new strategies coupling human genetics with model organisms have provided mechanistic insights into the molecular and developmental pathways underlying CHD pathogenesis, notably chromatin remodeling and ciliary signaling.

中文翻译：

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先天性心脏病：连接遗传学和发育的新兴主题。


尽管先天性心脏病 (CHD) 是最常见的可存活出生缺陷，但大多数 CHD 的病因仍不清楚。来自人类和脊椎动物模型的几条证据支持先心病的遗传因素，但基因座的极端异质性和缺乏明显的基因型-表型相关性限制了致病基因的发现。然而，基因组技术的最新进展允许对大量先心病患者的遗传异常进行详细评估。这导致了拷贝数变异和新生突变的鉴定，它们合计占 CHD 的 15%。此外，将人类遗传学与模式生物相结合的新策略为了解 CHD 发病机制的分子和发育途径提供了机制见解，特别是染色质重塑和纤毛信号传导。