Pediatric Genomics Discovery Program, Department of Pediatrics and Genetics, Yale University School of Medicine, United States.
Pediatric Genomics Discovery Program, Department of Pediatrics and Genetics, Yale University School of Medicine, United States.
Curr Opin Genet Dev. 2019 Jun;56:34-40. doi: 10.1016/j.gde.2019.05.003. Epub 2019 Jun 21.
Heterotaxy, a disorder in which visceral organs, including the heart, are mispatterned along the left-right body axis, contributes to particularly severe forms of congenital heart disease that are difficult to mitigate even despite surgical advances. A higher incidence of heterotaxy among individuals with blood kinship and the existence of rare monogenic disease forms suggest the existence of a genetic component, but the genetic and phenotypic heterogeneity of the disease have rendered gene discovery challenging. Next generation genomics in patients with syndromic, but also non-syndromic and sporadic heterotaxy, have recently helped to uncover new candidate disease genes, expanding the pool of genes already identified via traditional animal studies. Further characterization of these new genes in animal models has uncovered fascinating mechanisms of left-right axis development. In this review, we will discuss recent findings on the functions of heterotaxy genes with identified patient alleles.
内脏器官（包括心脏）沿左右体轴错位排列的异构症是一种疾病，会导致先天性心脏病的严重程度特别高，即使手术技术有所进步，也很难缓解。血缘关系个体中异构症的发病率较高，以及罕见的单基因疾病形式的存在，表明存在遗传成分，但该疾病的遗传和表型异质性使得基因发现具有挑战性。患有综合征的患者的下一代基因组学，以及非综合征和散发性异构症，最近有助于发现新的候选疾病基因，扩大了通过传统动物研究已经鉴定出的基因池。在动物模型中对这些新基因的进一步特征分析揭示了左右轴发育的迷人机制。在这篇综述中，我们将讨论具有已鉴定患者等位基因的异构症基因功能的最新发现。
