Prenatal diagnosis of BACs-on-Beads assay in 1520 cases from Fujian Province, China

Abstract

Background: The aim of this study was to evaluate the application of BACs-on-Beads (BoBs™) assay for rapid detection of chromosomal abnormalities for prenatal diagnosis (PND).

Methods: A total of 1520 samples, including seven chorionic villi biopsy samples, 1328 amniotic fluid samples, and 185 umbilical cord samples from pregnant women were collected to detect the chromosomal abnormalities using BoBs™ assay and karyotyping. Furthermore, abnormal specimens were verified by chromosome microarray analysis (CMA) and fluorescence in situ hybridization (FISH).

Results: The results demonstrated that the success rate of karyotyping and BoBs™ assay in PND was 98.09% and 100%, respectively. BoBs™ assay was concordant with karyotyping for Trisomy 21, Trisomy 18, and Trisomy 13, sex chromosomal aneuploidy, Wolf-Hirschhorn syndrome, and mosaicism. BoBs™ assay also detected Smith-Magenis syndrome, Williams-Beuren syndrome, DiGeorge syndrome, Miller-Dieker syndrome, Prader-Willi syndrome, Xp22.31 microdeletions, 22q11.2, and 17p11.2 microduplications. However, karyotyping failed to show these chromosomal abnormalities. A case of 8q21.2q23.3 duplication which was found by karyotyping was not detected by BoBs™ assay. Furthermore, all these chromosomal abnormalities were consistent with CMA and FISH verifications. According to the reports, we estimated that the detection rates of karyotyping, BoBs™, and CMA in the present study were 4.28%, 4.93%, and 5%, respectively, which is consistent with the results of a previous study. The respective costs for the three methods were about $135-145, $270-290, and $540-580.

Conclusion: BoBs™ assay is considered a reliable, rapid test for use in PND. A variety of comprehensive technological applications can complement each other in PND, in order to maximize the diagnosis rate and reduce the occurrence of birth defects.

Keywords: BoBs™; CMA; FISH; PND; karyotyping; microdeletions; microduplications.

Figure 1

The maps of aneuploidies involving Chromosomes 13, 18, and 21 and the sex chromosomes to which BoBs™ assay was applied. (a) Trisomy 13. (b) Trisomy 18. (c) Trisomy 21. (d) XXX. (e) XXY. (f) XYY. The blue dots represent the proportion of tested DNA compared with the male reference DNA. The red dots represent the proportion of tested DNA compared with female reference DNA. The green lines are at the normal signal range. 93 × 46 mm (300 × 300 DPI)

Figure 2

The maps within the detection range of BoBs™ assay. (a) SMS deletion syndrome (4.78 Mb lost in 17p11.2). (b) WHS deletion syndrome (35 Mb lost in 4p16.3p15.1). (c) WBS deletion syndrome (1.4 Mb lost in 7q11.23). (d) DGS deletion syndrome (1.8 Mb lost in 21q11.2). (e) MDS deletion syndrome (5.2 Mb lost in 17p11.3). (f) PWS deletion syndrome (5.7 Mb lost in 15q11.2q13.1). CMA: The red lines represent lost; the blue lines represent gain

Figure 3

The maps outside of the detection range of BoBs™ assay. (a) Xp22.31 microdeletions (1.2 Mb). (b) 22q11.2 microduplications (2.0 Mb) (c) 17p11.2 microduplications (4.8 Mb). (d) 8q21.2q23.2 duplication (28 Mb)

Figure 4

Mosaicism maps employing BoBs™, CMA, and FISH assays. (a) Yp11.31q11.21 duplication (15.3 Mb) and Yq11.221q11.23 deletion (10.7 Mb). (b) Xp22.33q11.21 deletion (62 Mb) and Xq21.31q28 deletion (68 Mb). FISH using DXZ1 and D18Z1 probes for the X and 18 chromosomes centromeres (green and turquoise signals, respectively). (c) Xp22.33q11.1 deletion (56 Mb) and Xq21.1q28 deletion (75 Mb). (d) Trisomy21 (mosaicism)