Research On The Application Of Copy Number Variation Sequencing In Prenatal Diagnosis

Objective:Through Copy number variation sequencing and Chromosome karyotype analysis of fetal chromosomes in amniotic fluid cells,to discuss the application value of CNV-seq technology in prenatal diagnosis.Methods:1.The pregnant women who attended the Maternal and Child Health Care Hospital of Shanxi Province from March 2019 to June 2020 were selected as the research objects.2.To extract amniotic fluid from 447 pregnant women with prenatal diagnosis indications,chromosome karyotype analysis and CNV-seq test were performed on each specimen.Then analyzed and compared two techniques to detect fetal chromosomal abnormalities.Follow up their pregnancy outcome.3.SPSS 23.0 was used to analyze the data,and the measurement data was expressed as mean±standard deviation.The chi-square test was used to compare the rates between groups,and P<0.05 was considered statistically significant.4.Obtain the approval of the ethics committee of Maternal and Child Health Care Hospital of Shanxi Province.Results:1.The success rate of CNV-seq detection in 447 cases of amniotic fluid samples was 100%,and the success rate of karyotype analysis was 99.55%(445/447).The failure of amniotic fluid cells culture resulted in the failure of karyotype analysis in 2 cases,accounting for 0.45%(2/447).2.Chromosome karyotype analysis detected 353 normal chromosomes cases and 92 chromosome abnormalities cases,and 2 cases of chromosome karyotype analysis could not be detected due to the failure of amniotic fluid cell culture.CNV-seq detected 309 normal chromosomes cases,and 138 chromosomal abnormalities cases.3.In 353 amniotic fluid specimens with normal karyotype analysis,CNV-seq detected 55 microdeletions and microduplications,including 6 cases with pathogenic copy number variants,2 cases with likely pathogenic copy number variants,17 cases with benign copy number variants,6 cases with likely benign copy number variants,and24 cases with variants of uncertain significance.The pathogenic or likely pathogenic copy number variants accounted for 2.27%(8/353).2 specimens with failed amniotic fluid cells culture CNV-seq test was successful,and a case was normal,another was VUS.4.Compared with CNV-seq combined karyotype analysis and chromosome karyotype analysis,the detection rate of fetal chromosomal abnormalities was statistically significant difference(P < 0.05).Compared with CNV-seq combined karyotype analysis and CNV-seq,the detection rate of fetal chromosomal abnormalities was no significant difference(P>0.05).Compared with the rate of fetal chromosomal abnormalities detected by CNV-seq and chromosome karyotype analysis,the difference was statistically significant(P<0.05).5.In 447 cases of amniotic fluid samples,9 cases of fetal chromosome mosaicism were detected,accounting for 2.01%(9/447),8 cases were detected by karyotype analysis,accounting for 1.79%(8/447),and 6 cases were detected by CNV-seq,accounted for 1.34%(6/447).Conclusion:1.CNV-seq can detect more pathogenic copy number variations,as well as newly discovered CNVs,but it cannot detect chromosome balanced translocations,inversions and other balanced structural abnormalities.2.CNV-seq avoids cell culture and it can accurately detect low proportions of mosaicism.3.The combined application of CNV-seq and chromosome karyotype analysis can detect fetal chromosomal abnormalities comprehensively and effectively,it can improve the detection rate of prenatal diagnosis.It has important value in prenatal diagnosis.