Stillbirth after 20 weeks gestation happens in 1 in 200 pregnancies and occurs more commonly than neonatal loss and sudden infant death syndrome (SIDs) combined. The stillbirth rate is several times greater in low as opposed to high-resource countries. However, among high-resource countries, although a lower overall stillbirth rate exists, there has been little change for several decades. Molecular genetic technologies are emerging as important contributors to our understanding of stillbirth. Initially, genetic etiologies included alterations in chromosome number or structure such as aneuploidy and microduplications and deletions. More recently, next-generation sequencing analysis in two genetic conditions, Smith Lemli Optiz Syndrome (SLOs) and the channelopathy disorders (such as long QT syndrome (LQTS)) provide examples into the association of pathogenic gene variants with stillbirth. Although these specific conditions individually account for only a small number of stillbirths, investigating these disorders provides a new and innovative approach for further understanding genetic contributors to adverse pregnancy outcomes. Our knowledge of the role of genetic disease as an etiology for stillbirth is elementary. Genomic interrogation of maternal-fetal genotypes, gene-gene, and genotype-environment interaction is lacking in stillbirth research. At the DNA sequence level, further investigation of variants of unknown significance is an opportunity for exploration of biologic pathways of importance to pregnancy loss. This review concentrates on SLO as an example of a single gene disorder with a high carrier but low affected liveborn proband rate. The channelopathy disorders are included as initial examples of genetic conditions with variable presentation including an association with sudden infant death syndrome. Highlighted are the challenges when numerous genes and variants are involved, and the task of assigning pathogenicity. The advantages and limitations of genetic evaluations are presented and avenues for further research considered.

中文翻译：

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基因创新和我们对死产的理解。

妊娠20周后的死产每200例中就有1例发生，并且比新生儿流失和婴儿猝死综合症（SID）的总和还多。资源贫乏国家的死产率是低资源国家的几倍。然而，在资源丰富的国家中，尽管总体死产率较低，但几十年来几乎没有变化。分子遗传技术正在成为我们对死胎的理解的重要贡献者。最初，遗传病因包括染色体数目或结构的改变，例如非整倍性以及微复制和缺失。最近，在两种遗传条件下进行的下一代测序分析 Smith Lemli Optiz综合症（SLOs）和通道病（例如长QT综合症（LQTS））为致病性基因变异与死胎的关联提供了实例。尽管这些特殊情况仅占少数死产，但是对这些疾病的研究为进一步了解导致不良妊娠结局的遗传因素提供了一种新的创新方法。我们对遗传疾病作为死产病因的作用的知识是基本的。死产研究缺乏母婴基因型，基因-基因和基因型-环境相互作用的基因组研究。在DNA序列水平上，进一步研究未知意义的变异体是探索对妊娠流失重要的生物学途径的机会。本文以SLO为例，以单基因疾病为例，该基因携带者高，但活检先证率低。通道病疾病是遗传状况的初始例子，表现形式多样，包括与婴儿猝死综合症的关联。突出显示了涉及大量基因和变体时的挑战以及分配致病性的任务。提出了遗传评估的优缺点，并考虑了进一步研究的途径。突出显示了涉及大量基因和变体时的挑战以及分配致病性的任务。提出了遗传评估的优缺点，并考虑了进一步研究的途径。突出显示了涉及大量基因和变体时的挑战以及分配致病性的任务。介绍了遗传评估的优缺点，并考虑了进一步研究的途径。