| Summary: | Background Karyotyping and genome copy number variation sequencing (CNV-seq) are two techniques frequently used in prenatal diagnosis. This study aimed to explore the diagnostic potential of using a combination of these two methods in order to provide a more accurate clinical basis for prenatal diagnosis. Methods We selected 822 pregnant women undergoing amniocentesis and separated them into six groups according to different risk indicators. Karyotyping and CNV-seq were performed simultaneously to compare the diagnostic performance of the two methods. Results Among the different amniocentesis indicators, abnormal fetal ultrasounds accounted for 39.29% of the total number of examinees and made up the largest group. The abnormal detection rate of non-invasive prenatal testing (NIPT) high risk was 37.93% and significantly higher than the other five groups (P < 0.05). The abnormal detection rate of mixed indicators was significantly higher than the history of the adverse reproductive outcomes group (P = 0.0151). The two methods combined found a total of 119 abnormal cases (14.48%). Karyotyping detected 57 cases (6.93%) of abnormal karyotypes, 30 numerical aberrations, and 27 structural aberrations. CNV-seq identified 99 cases (12.04%) with altered CNVs, 30 cases of chromosome aneuploidies, and 69 structural aberrations (28 pathogenic, eight that were likely pathogenic, and 33 microdeletion/duplication variants of uncertain significance (VUS)). Thirty-seven cases were found abnormal by both methods, 20 cases were detected abnormally by karyotyping (mainly mutual translocation and mostly balanced), and 62 cases of microdeletion/duplication were detected by CNV-seq. Steroid sulfatase gene (STS) deletion was identified at chromosome Xp22.31 in three cases. Postnatal follow-up confirmed that babies manifested skin abnormalities one week after birth. Six fetuses had Xp22.31 duplications ranging from 1.5 Kb to 1.7 Mb that were detected by CNV-seq. Follow-up showed that five babies presented no abnormalities during follow-up, except for one terminated pregnancy due to a history of adverse reproductive outcomes. Conclusion The combination of using CNV-seq and karyotyping significantly improved the detection rate of fetal pathogenic chromosomal abnormalities. CNV-seq is an effective complement to karyotyping and improves the accuracy of prenatal diagnosis.
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