Experience Using a Rapid Assay for Aneuploidy and Microdeletion/Microduplication Detection in over 2,900 Prenatal Specimens

Abstract

Background: While microarray testing can identify chromosomal abnormalities missed by karyotyping, its prenatal use is often avoided in low-risk pregnancies due to the possible identification of variants of uncertain significance (VOUS). Methods: We tested 2,970 prenatal samples of all referral indications using a rapid BACs-on-Beads-based assay with probes for sex chromosomes, common autosomal aneuploidies, and 20 microdeletion/microduplication syndromes, designed as an alternative to microarray in low-risk pregnancies and an alternative to rapid aneuploidy testing in pregnancies also undergoing microarray analysis. Results: Interpretable results were obtained in 2,940 cases (99.0%), with 89% receiving results in 1 day. Aneuploidies were detected in 7.3% and partial chromosome abnormalities in 0.45% (n = 13), including 5 referred for maternal age, abnormal maternal serum screen, or isolated ultrasound markers. The added detection above karyotype was 1 in 745 in lower-risk cases with normal ultrasounds or isolated ultrasound markers/increased nuchal measurements and 1 in 165 for fetuses with structural/growth abnormalities. Neither false negatives nor false positives were found within test limitations. Female polyploidy could not be detected, while polyploidies with Y chromosomes were suspected and confirmed through additional analysis. Conclusion: When combined with karyotyping, this assay provides increased interrogation of specific chromosomal regions, while limiting VOUS identification.

Application of the BACs‐on‐Beads™ assay for rapid prenatal detection application of BoBs™ for PND of aneuploidies and microdeletions

“…These cases all involved microdeletions or microduplications, which conventional karyotyping might not be able to detect because they are less than 5 Mb in size—the resolution limit of the method, unless the banding is above the 750‐band level (Choy et al, ); indeed, false‐negative diagnoses occurs most often in karyotyping when the abnormality is less than 5 Mb (Shaffer & Bui, ). Thus, from a cytogenetic point of view, the BoBs™ assay could offer extra diagnostic benefits compared with karyotyping because it provides more diversity and sensitivity to detect microdeletions and microduplications (Garcia‐Herrero et al, ; Rosenfeld et al, ; Sheath, Duffy, Asquith, Love, & George, ).…”

Application of karyotype analysis combined with BACs-on-Beads for prenatal diagnosis

“…Prenatal diagnosis is the only way to prevent birth of children with defects (5). Therefore, early screening, early diagnosis, and timely termination of pregnancy are important measures to reduce birth defects (6). …”

Combined use of bacterial artificial chromosomes-on-beads with karyotype detection improves prenatal diagnosis

“…A study by Rosenfeld et al [19] in the United States examined 2940 prenatal samples using a quick BoBs™ assay, in which 89% of the results were obtained within 1 day. There were 7.9% aneuploidies and 0.45% partial chromosomal abnormalities.…”

“…There were 7.9% aneuploidies and 0.45% partial chromosomal abnormalities. When combined with karyotyping, these researchers detected 1 of 745 cases that had low risk (such as a normal ultrasound or isolated ultrasound marker and increased nuchal measurements) and 1 of 165 cases that had fetal structural or growth abnormalities [19].…”