It is well established that embryonic chromosomal abnormalities (both in the number of chromosomes and the structure) account for 50% of early pregnancy losses. However, little is known regarding the potential differences in the incidence and distribution of chromosomal abnormalities between patients with sporadic abortion (SA) and recurrent pregnancy loss (RPL), let alone the role of submicroscopic copy-number variations (CNVs) in these cases. The aim of the present study was to systematically evaluate the role of embryonic chromosomal abnormalities and CNVs in the etiology of RPL compared with SA. Over a 3-year period, 1556 fresh products of conception (POCs) from miscarriage specimens were investigated using single nucleotide polymorphism array (SNP-array) and CNV sequencing (CNV-seq) in this study, along with further functional enrichment analysis. Chromosomal abnormalities were identified in 57.52% (895/1556) of all cases. Comparisons of the incidence and distributions of chromosomal abnormalities within the SA group and RPL group and within the different age groups were performed. Moreover, 346 CNVs in 173 cases were identified, including 272 duplications, 2 deletions and 72 duplications along with deletions. Duplications in 16q24.3 and 16p13.3 were significantly more frequent in RPL cases, and thereby considered to be associated with RPL. There were 213 genes and 131 signaling pathways identified as potential RPL candidate genes and signaling pathways, respectively, which were centered primarily on six functional categories. The results of the present study may improve our understanding of the etiologies of RPL and assist in the establishment of a population-based diagnostic panel of genetic markers for screening RPL amongst Chinese women.

中文翻译：

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复发性妊娠丢失中拷贝数变异和可能的候选基因的表征

众所周知，胚胎染色体异常（在染色体数目和结构上）占早期妊娠损失的50％。然而，关于零星流产（SA）和复发性流产（RPL）患者之间染色体异常发生率和分布的潜在差异知之甚少，更不用说亚显微拷贝数变异（CNV）在这些情况下的作用了。本研究的目的是系统地评估与SA相比，RPL的病因中胚胎染色体异常和CNV的作用。在三年的研究中，使用单核苷酸多态性阵列（SNP-array）和CNV测序（CNV-seq）在流产标本中研究了1556种新鲜的受孕产品（POC），以及进一步的功能丰富分析。在所有病例中，发现染色体异常的比例为57.52％（895/1556）。比较了SA组和RPL组以及不同年龄组的染色体异常的发生率和分布。此外，在173个病例中鉴定出346个CNV，包括272个重复，2个缺失和72个重复以及缺失。在RPL情况下，在16q24.3和16p13.3中进行重复的频率明显更高，因此被认为与RPL相关。分别有213个基因和131个信号通路被确定为潜在的RPL候选基因和信号通路，它们主要集中在六个功能类别上。