Clinical Utility of the Prenatal BACs-on-Beads™ Assay in Invasive Prenatal Diagnosis.

Yu Jiang,Yunshen Ge,Qichang Wu,Yanhong Zhang,Yanru Huang,Yulin Zhou,Jian Zhang,Lili Wu

doi:10.3389/fgene.2021.789625

Abstract

Background: The prenatal BACs-on-Beads™ (PNBoBs™) assay has been applied worldwide for prenatal diagnosis. However, there are neither guidelines nor consensus on choosing patients, sample types, or clinical pathways for using this technique. Moreover, different perspectives have emerged regarding its clinical value. This study aimed to evaluate its clinical utility in the context of clinical practice located in a prenatal diagnostic center in Xiamen, a city in southeast China. Methods: We tested 2,368 prenatal samples with multiple referral indications using both conventional karyotyping and PNBoBs™. Positive results from PNBoBs™ were verified using current gold-standard approaches. Results: The overall rates for the detection of pathogenic copy number variation (pCNV) by karyotyping and PNBoBs™ were 1.9% (46/2,368) and 2.0% (48/2,368), respectively. The overall detection rate of karyotyping combined with PNBoBs™ for pCNV was 2.3% (54/2,368). A total of 13 cases of copy number variation (CNV)with a normal karyotype were detected by PNBoBs™. Another case with a normal karyotype that was detected as a CNV of sex chromosomes by PNBoBs™ was validated to be maternal cell contamination by short tandem repeat analysis. Conclusion: Karyotyping combined with PNBoBs™ can improve both the yield and efficiency of prenatal diagnosis and is appropriate in the second trimester in all patients without fetal ultrasound anomalies who undergo invasive prenatal diagnosis.

Highlights

We present our recommendations on these issues based on our analysis of laboratory findings from one of the largest prenatal diagnosis centers in southeastern China
The 2,368 cases were categorized into seven subgroups by primary clinical indications for prenatal diagnosis
Due to the lack of sufficient validation data, at this stage, we propose verifying incidental findings by chromosome microarray analysis (CMA)/copy number variation sequencing (CNV-seq) to assess the pathogenicity of these CNVs

Summary

Introduction

To date, there is still no consensus on which patients undergoing invasive prenatal diagnosis are appropriate for TM PNBoBs testing and how to use its results to make clinical decisions. With the use of genome-wide copy-number variation detection techniques, including chromosome microarray analysis (CMA) and copy number variation sequencing (CNV-seq) in prenatal diagnosis (Stosic et al, 2018; Wang H. et al, 2020), doubts have been raised. TM regarding the clinical utility of PNBoBs in invasive prenatal diagnosis (Xu et al, 2020). We present our recommendations on these issues based on our analysis of laboratory findings from one of the largest prenatal diagnosis centers in southeastern China. This study aimed to evaluate its clinical utility in the context of clinical practice located in a prenatal diagnostic center in Xiamen, a city in southeast China

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Methods

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Conclusion