Diagnostic accuracy of the BACs-on-Beads assay versus karyotyping for prenatal detection of chromosomal abnormalities: a retrospective consecutive case series

Authors


Abstract

Objective

To evaluate the diagnostic performance of the BACs-on-Beads (BoBs) assay for prenatal detection of chromosomal abnormalities.

Design

Retrospective study.

Setting

Tertiary prenatal diagnosis centre.

Population

Women referred for prenatal diagnosis.

Methods

We retrieved 2153 archived DNA samples collected between January 2010 and August 2011 for the BoBs assay. These samples had previously been tested by quantitative fluorescence polymerase chain reaction (QF-PCR) and karyotyping. In the BoBs assay a sample was defined as normal disomic when the ratio of the fluorescence intensities in a chromosome locus lay within the threshold (mean ratio ± 2SD), and as deleted or duplicated when the ratio was below the lower threshold (0.6–0.8) or above the upper threshold (1.3–1.4), respectively. The BoBs results were further validated by microarray and compared in a blinded manner with the original QF-PCR and karyotyping results.

Main outcome measures

Concordance of any numerical, structural, and submicroscopic chromosomal abnormalities between the methods.

Results

BACs-on-Beads was similar to karyotyping and QF-PCR in detecting trisomy 13, trisomy 18, trisomy 21, and sex chromosomal aneuploidies, and superior to QF-PCR in detecting major structural abnormalities (53.3 versus 13.3%) and mosaicism (28.6 versus 0%) involving chromosomal abnormalities other than the common aneuploidies. BoBs detected six microdeletion syndromes missed by karyotyping and QF-PCR; however, BoBs missed two cases of triploidy identified by QF-PCR. Therefore, the sensitivity of BoBs is 96.7% (95% CI 92.6–98.7%), and its specificity is 100% (95% CI 99.8–100%).

Conclusions

BACs-on-Beads can replace QF-PCR for triaging in prenatal diagnosis, and gives a better diagnostic yield than current rapid aneuploidy tests.

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