Application of prenatal bacterial artificial chromosome-on-beads identification/isolation technology in the diagnosis of chromosomal aneuploidy and microdeletion/microduplication syndrome / 中华检验医学杂志

ABSTRACT

Objective:To explore the indication of bacterial artificial chromosome-on-beads identification/separation technology in prenatal diagnosis and its application value.Methods:The inclusion criteria were as follows age ≥35 years, high risk/critical risk of serological prenatal screening, high risk of non-invasive gene testing (NIPT), abnormal ultrasonic indexes or adverse pregnancy history. From April 2016 to December 2020, 3579 amniotic fluid samples collected from pregnant women with singletons were detected by bacterial artificial chromosome-on-beads identification/separation technique (BoBs) and G-banding karyotype analysis simultaneously. The aneuploid abnormality/microdeletion/microdeletion samples detected by karyotype analysis or BoBs were verified by fluorescence in situ hybridization (FISH)/SNP array as needed.Results:(1) The percentage of samples with indications of advanced maternal age, high risk of NIPT and high risk of serological screening was 89.44%(3 201/3 579), the detection rate of aneuploidy was 96.19%(202/210), and the detection rate of microdeletion/microduplication was 87.5%(28/32),the total abnormal detection rate was 95.04% (230/242). The samples with abnormal ultrasonic indexes, adverse pregnancy history and critical risk indications of serological screening in the second trimester accounted for 10.66%, and the abnormality of aneuploidy and micro-duplication/micro-deletion was 4.96%. (2) 198 common chromosome aneuploidies (13/18/21/X/Y) were detected by BoBs, and 12 cases with chimeras ≥20% were found, which were consistent with karyotype results. Two copies of 21-trisomy, three copies of X/Y, seven copies of 2, 7, 8, 9, 10, 20, mar karyotype chimerism, eight copies of arm inversion and five copies of translocation outside the detection range of probes were detected by karyotype analysis. The sensitivity, specificity and false negative rate of BoBs detection for five aneuploidies were 94.6%(210/222), 100% and 5.4%(12/222), respectively. BoBs and karyotype analysis detected 32 and 9 cases of microdeletions/microduplications respectively. Compared with single karyotype analysis, the combined application of G-banding karyotype analysis and BoBs can detect an additional 9.4% (23/244)positive samples.Conclusion:The samples with elder age, high risk of NIPT, and high risk of serological screening are more suitable as indications for the application of BoBs in prenatal diagnosis.