Congenital heart defect is one of the most common structural birth defects in the human population. It is highly associated with heterotaxy, a birth defect involving randomized left-right patterning of visceral organ situs. Large scale mouse forward genetics have led to the finding of a central role for cilia in CHD pathogenesis, with some cilia and non-cilia mutations causing CHD with heterotaxy. Interestingly, many of the mutations causing CHD with heterotaxy can give rise to three laterality outcomes comprising normal situs solitus, mirror symmetric situs inversus totalis, or randomized situs with heterotaxy. Given CHD is largely observed only with heterotaxy, this suggests a new paradigm is needed for investigating the genetics of CHD associated with heterotaxy. Furthermore, analysis of data from multiple large birth cohorts have independently confirmed a broader involvement of laterality disturbance in CHD. This was demonstrated by the common cooccurrence of rare laterality defects with CHD lesions of a wide spectrum. These findings suggest left-right patterning is tightly intertwined with the developmental processes that regulate cardiac morphogenesis and its disturbance may contribute to all types of CHD even in the absence of laterality defects.

中文翻译：

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先天性心脏病的左，右模式超出了异质性。

先天性心脏缺陷是人类中最常见的结构性出生缺陷之一。它与异源性高度相关，异质性是一种先天缺陷，涉及内脏器官位置的随机左右模式。大规模的小鼠正向遗传学已导致纤毛在冠心病发病机理中的重要作用的发现，一些纤毛和非纤毛突变会导致CHD异位。有趣的是，许多导致具有异位性CHD的突变可引起三种偏侧性结局，包括正常的孤立位置，镜像对称的总体位置或带有异位的随机位置。鉴于CHD在很大程度上只观察到了异位症，这表明需要一种新的范式来研究与异位症相关的CHD的遗传学。此外，对来自多个大出生队列的数据进行的分析已独立确认，冠心病的偏侧性疾病涉及范围更广。罕见的偏侧缺陷与广泛的CHD病变的常见共存证明了这一点。这些发现表明左右模式与调节心脏形态发生的发育过程紧密地交织在一起，即使没有横向缺陷，其干扰也可能导致所有类型的冠心病。