Analysis of copy number variations and candidate genes in recurrent pregnancy loss

Background Recurrent pregnancy loss (RPL) is often associated with genetic factors. This study investigates chromosomal abnormalities in RPL by analyzing copy number variations (CNVs) and single-nucleotide variants (SNVs). Methods We conducted a retrospective analysis of 400 RPL patients, with 393 successfully analyzed using CNV-seq and single nucleotide polymorphism (SNP)-array after excluding maternal cell contamination (MCC). Additionally, 16 families with normal results underwent whole exome sequencing (WES). Results Among the patients, 187 (47.6%) showed normal results, while 206 (52.4%) exhibited abnormalities, including 152 aneuploidies (73.8%), 37 CNVs (18.0%), and 17 triploidies (8.3%). Statistical analysis revealed a significant increase in chromosomal abnormalities with advancing maternal age, but no significant differences in rates were observed before 24 weeks of pregnancy in patients with two or more miscarriages. We identified 28 pathogenic (P)/likely pathogenic (LP) CNVs and six P/LP SNVs, implicating 808 morbid genes. Enrichment analysis and protein-protein interaction (PPI) network construction revealed 69 key genes in critical pathways, with IL6 , TNF , and ACTB as hub genes. Discussion These findings contribute to establishing genetic markers for RPL screening in the Chinese population, enhancing our understanding of miscarriage etiology and facilitating prenatal diagnosis.