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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.
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Objective@#To investigate the value of karyotype analysis, bacterial artificial chromosomes-on-beads (BoBs), chromosome microarray analysis (CMA) and fluorescence in situ hybridization (FISH) in the diagnosis of sex chromosome numerical and structural abnormalities.@*Methods@#Conventional G-banding staining technique was used to analyze the karyotypes of amniotic fluid cells and parental peripheral blood cells in two pregnancies with prenatal diagnosis indications. Sex chromosome numerical and structural abnormalities were analyzed based on the results of G-banding, BoBs, CMA and FISH.@*Results@#The results of G-banding karyotype analysis showed that there were mosaics in amniotic fluid cells collected from both cases. Karyotype of Case A was 45,X[25]/46,X,idic(Y)(q11.2?)[6], and Case B was 45,X[39]/46,X,psu idic(X)(q21.32?)[44]. Parental peripheral blood karyotypes of both families were normal. Prenatal BoBs indicated copy number abnormalities in sex chromosomes (Y chromosome in Case A and X chromosome in Case B). CMA results suggested a 20.1 Mb duplication in Yp11.32q11.222, and a 7.7 Mb deletion in Yq11.222q11.23 in fetus A with possible karyotype of 46,X,idic(Y)(q11.222); for fetus B, a 92.0 Mb duplication in Xp22.33q21.32, and a 63.0 Mb deletion in Xq21.32q28 were detected, and the karyotype might be 46,X,psu idic(X)(q21.32). The mid-term FISH test of amniotic fluid cells showed that 90% of the amniotic cells from Case A were 45,X, and 10% were 46,X,idic(Y)(q11.2); about 38% were 45,X, and 62% were 46,X,psu dic(X)(q21.3) from Case B.@*Conclusions@#Numerical and structural abnormalities of sex chromosomes could be accurately diagnosed by combination of several methods including G-banding karyotype analysis, prenatal BoBs, CMA and FISH, which would help to effectively reduce birth defects.