Bacterial artificial chromosomes (BACs)eon-Beads (BoBs) assay and copy number variation sequencing (CNV-seq) are two frequently used methods in today's prenatal diagnosis. Several studies were conducted to investigate the performance of each approach, but they were never compared side by side. In this article, a comprehensive comparison of BoBs and CNV-seq was conducted using 1876 amniotic fluid and umbilical cord blood samples collected from Fujian Maternity and Child Health Hospital between 2015 and 2019. Karyotyping was used as the gold standard for chromosome structure variation, and chromosomal microarray analysis was performed to validate inconsistent results. Overall, 174 cases of confirmed chromosome anomalies were detected, including 73 chromosomal aneuploidies, 10 mosaics, 30 pathogenic CNVs, and 61 other structural anomalies. BoBs and CNV-seq achieved a 100% concordance in all 55 pathogenic euchromosome aneuploidies, but CNV-seq had a higher detection rate in sex chromosome aneuploidy and mosaic identification. For CNV detection, all of the 20 pathogenic CNVs discovered by the BoBs assay also were identified by CNV-seq and 10 additional pathogenic CNVs were observed by CNV-seq. The results of this study showed that CNV-seq was a reliable and more favorable method in terms of detection rate, costs, and disease range. In combination with karyotyping, CNV-seq could improve the efficiency and accuracy of a prenatal diagnosis to alleviate maternal emotional anxiety and deduce birth defects.

The prenatal BACs-on-Beads™ (BoBs) assay was introduced for rapid detection of abnormalities of chromosomes 13, 18, 21, X, and Y and specific nine significant microdeletion syndromes. The ability of prenatal BoBs to detect mosaicism ranged from 20 to 40%. However, there have been no prenatal studies of sex chromosome mosaicism in prenatal BoBs. Therefore, the present study was performed with an aim to uncover the detection level of sex chromosome mosaicism that application of prenatal BoBs assay, and then to assess the sensitivity of prenatal BoBs assay, thereby improving the prenatal diagnostic accuracy. A total of 31 samples of amniotic fluid (AF) and umbilical cord blood (UCB) for prenatal diagnosis were collected, and the results were confirmed through karyotyping, single nucleotide polymorphism microarray (SNP-array) and copy number variation sequencing (CNV-seq). 23 cases of sex chromosome mosaicism were prompted abnormal by prenatal BoBs, the minimum detection level of mosaicism was about 6% as detected by karyotype. The overall sensitivity of prenatal BoBs in the detection of sex chromosome mosaicism was 74.2% (23/31). This study evaluated the effectiveness of prenatal BoBs for detecting sex chromosome mosaicism in prenatal diagnosis, and the results will provide valuable information for genetic counseling.