Chromosomal Copy Number Variation Analysis in Pregnancy Products from Recurrent and Sporadic Miscarriage Using Next-Generation Sequencing.

Chromosomal abnormality is one of the causes of fetal miscarriage. The potential differences of fetal chromosomal abnormalities in sporadic miscarriage (SM) and recurrent miscarriage (RM) remain unclear. The purpose of this study was to investigate copy number variations (CNVs) in SM and RM to provide useful genetic guidance for pregnancy and prenatal diagnosis. Four hundred eight samples of aborted fetuses were analyzed by CNV sequencing, and further functional enrichment analysis was performed. Chromosomal abnormalities were identified in 218 (53.4%) fetuses. There were 62 cases (15.2%) with structural chromosomal abnormalities, including 41 with VUS CNVs, 8 with pathogenic CNVs (pCNVs), and 5 with likely pCNVs. Duplications or deletions of 7p22, 8p22, 8p23, and Xp22.31 were significantly more common in RM cases and therefore believed to be related to RM. A total of 289 genes were identified, and 29 different functions were enriched as potential RM candidate genes and functions, which were mainly concentrated in 4 functional categories: chemokines and chemotaxis, protease activity and protein modification, defense response to bacterial and fungal infections, and immune response. The results of this study may improve our understanding of the etiology of RM and contribute to the establishment of a population-based genetic marker information for RM.