Role of subminiature and recurrent chromosome copy number variations in recurrent spontaneous abortion
Objective To explore the key copy number variation(CNV)regions,abortion candidate genes and signaling pathways associated with recurrent spontaneous abortion(RSA).Methods A retrospective cohort study was conducted based on the data of 1 870 miscarriage cases of RSA patients who received CNV analysis by high-throughput sequencing technology in the Laboratory Medicine Department of the Third Affiliated Hospital of Zhengzhou University from January 2016 to September 2022.These cases were divided into different groups based on the age of miscarriage and gestational age of the pregnant women.Chi-square test or Fisher's exact test was used to analyze the distribution of chromosome abnormalities and CNV.Gene functions and signaling pathways in RSA-related CNV were identified by gene enrichment analysis.Results Among the 1 870 tissues,1 001(53.53%)cases were detected with chromosomal abnormalities.A total of 140 CNVs were detected in 93 tissues(9.29%),including 34 submicroscopic CNVs(segment<10 Mb)and 106 large CNVs with segment≥10 Mb.Submicroscopic pathogenicity CNVs with statistical differences were involved 1p36.33p36.23,2q37.3,4p16.3,22q11.21(χ2=6.99,P=0.008)in early RSA embryos(≤12 weeks).16p11.2 and Xp11.23p11.22 microdeletion were firstly reported in abortion cases.Significantly recurrent large CNVs were mainly involved 18q22q23(del/dup),4p16p15,9p24p22,8p23p22,and Xp22.3 regions,and the candidate genes mainly concentrated on PI3K-Akt and JAK-STAT signaling pathway.Conclusion Rare submicroscopic CNVs and recurrent large CNVs were associated with RSA in early pregnancy.GO and KEGG database analysis revealed potential abortion candidate genes and signaling pathways,providing new information for the genetic etiology of RSA.
Recurrent spontaneous abortionHigh-throughput sequencingCopy number variations
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