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A single-center retrospective study of G-band karyotyping and chromosomal microarray analysis (CMA) for the invasive prenatal diagnosis of 6159 fetuses with ultrasound abnormalities was conducted. This study aimed to investigate the incidence rates of chromosomal abnormalities and pregnancy outcomes and postpartum clinical manifestations by long-term follow-up and to explore the correlation between different types of prenatal ultrasound abnormalities and pathogenic chromosomal abnormalities. The overall incidence of pathogenic chromosomal aberrations in fetuses with ultrasound abnormalities was 7.58% (467/6159), which comprised 41.7% (195/467) with chromosome number abnormalities, 57.6% (269/467) with pathogenic copy-number variations (pCNVs), and 0.64% (3/467) with uniparental disomy (UPD). In addition, 1.72% (106/6159) with likely pathogenic copy-number variations (lpCNVs) and 3.04% (187/6159) with variants of unknown significance (VOUS) were detected by CMA. Ultrasound abnormalities were categorized into structural anomalies and soft marker anomalies. The incidence rate of pathogenic and likely pathogenic chromosomal abnormalities was significantly higher among fetuses with structural anomalies than soft markers (11.13% vs 7.59%, p < 0.01). We retrospectively analyzed the prenatal genetic outcomes for a large cohort of fetuses with different types of ultrasound abnormalities. The present study showed that the chromosomal abnormality rate and clinical outcomes of fetuses with different types of ultrasound abnormalities varied greatly. Our data have important implications for prenatal genetic counseling for fetuses with different types of ultrasound abnormalities., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Background: Central nervous system (CNS) abnormalities are a group of serious birth defects associated with high rates of stillbirths, infant death, or abnormal development, and various disease-causing copy number variations play a much more important role in the etiology of CNS abnormalities. This study intends to present a retrospective study of the prenatal diagnosis and the pregnancy outcome of fetuses diagnosed with CNS abnormalities, and evaluate the clinical value of chromosomal microarray analysis (CMA) in prenatal diagnosis of CNS abnormalities., Methods: A total of 356 fetuses with CNS abnormalities with or without other ultrasound abnormalities subjected to invasive prenatal diagnosis at the first affiliated hospital of Air Force Medical University from January 2015 to August 2018. All cases have performed both karyotyping and CMA concurrently, but 20 fetuses with chromosome aneuploidy were excluded in the current study., Results: The CMA identified pathogenic copy number variants (pCNVs) in 27/336 (8.03%) fetuses, likely pCNVs in 8/336 (2.38%) fetuses, and variants of unknown significance (VOUS) in 11/336 (3.27%) fetuses. A total of 222 cases had single CNS abnormalities and the pCNVs detection rate was 5.86% (13/222), the remaining 114 cases including CNS abnormalities plus other structural abnormalities, ultrasonographic soft markers and two or more CNS abnormalities, the pCNVs detection rate was 12.3% (14/114)., Conclusions: Fetuses with CNS abnormalities have a higher risk of chromosomal abnormalities, our study showed that CNVs play an important role in the etiology of CNS abnormalities. The application of CMA could increase the detection rate of pCNVs causing CNS abnormalities., (© 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals LLC.)

Background: The present study aimed to determine the accuracy (Z-value) of non-invasive prenatal testing (NIPT) results for sex chromosome aneuploidy (SCA) in routine clinical practice., Methods: Among a cohort of 12505 pregnant females, maternal plasma samples collected from our hospital were utilized for SCA analysis by NIPT detection. The positive samples were validated through an invasive procedure and karyotyping analysis. The predictive value from positive samples in sex chromosomes was compared to analyze the accuracy of the Z-value., Results: There were 65 females with sex chromosome abnormalities within 12,505 pregnant females in the NIPT detection, which was validated by karyotype analysis of amniotic fluid puncture through sequencing, as well as bioinformatics analysis, with 18 true-positive samples. The true-positive results with 45,X, 47,XXY, 47,XXX and 47,XYY karyotypes predicted by NIPT were 14.29%, 50.00%, 66.67% and 71.43%, respectively. Among sex chromosome cases, the findings indicated that positive NIPT results with Z ≥ 9 show a higher accuracy., Conclusions: The findings of the present study demonstrate that the positive predictive value of NIPT for sex chromosome abnormalities is distinctive. The positive predictive value was highest for 47,XYY and lowest for 45,X. Additionally, the Z-value results are considered to be correlated with the accuracy of NIPT, although further studies need to be made., (© 2020 John Wiley & Sons, Ltd.)

Objective: To evaluate the diagnostic accuracy of the BACs-on-Beads (BoBs) assay for the rapid diagnosis of common aneuploidies and microdeletion syndromes., Methods: BACs-on-Beads and chromosomal karyotyping were used for detecting 3647 cases of amniotic fluid samples with indications for prenatal diagnosis, which were collected from January 2015 to June 2017 in Xijing Hospital. Fluorescence in situ hybridization (FISH) or chromosomal microarray analysis (CMA) provided further validation., Results: The overall abnormality detection rate (BoBs combined with karyotyping) was 7.73% (282/3647). A total of 209 chromosomal aneuploidies, 10 mosaic cases, 11 microdeletion/microduplication syndromes, and 52 structural abnormalities were observed. Both assays were concordant for trisomy 21 (4.22%, 154/3647), trisomy 18 (0.69%, 25/3647), trisomy 13 (0.05%, 2/3647), and sex chromosome aneuploidies (0.77%, 28/3647). Meanwhile, DiGeorge syndrome (0.05%, 2/3647), 22q11.2 microduplication (0.08%, 3/3647), Smith-Magenis syndrome (0.03%, 1/3647), 17p11.2 microduplication (0.03%, 1/3647), Wolf-Hirschhorn syndrome (0.03%, 1/3647), Williams-Beuren syndrome (0.03%, 1/3647), Cri du Chat syndrome (0.03%, 1/3647), and Miller-Dieker syndrome (0.03%, 1/3647) were identified by BoBs assay, thus giving the incidence of the detection of these syndromes of 0.30% (11/3647)., Conclusion: BACs-on-Beads assay is a reliable test for rapid detection of common aneuploidies and microdeletion syndromes, combining with karyotyping, FISH, and CMA, to improve the efficiency and accuracy of prenatal diagnosis to alleviate maternal emotional anxiety.

Background: Non-invasive prenatal testing (NIPT) is extensively used in the detection of fetal trisomies 21, 18, and 13, which is promptly becoming a common clinical practice. Concerned about the clinical application of non-invasive detection of the fetal autosomal duplications or deletion., Case Presentation: A 34-year-old, healthy pregnant woman was referred to the First Affiliated Hospital of the Air Force Medical University. The ultrasound examination indicates that low-lying placenta, the fetus has a left ventricular bright spot and small amount of pericardial effusion. NIPT was chosen to further screen for fetal chromosomal abnormalities. NIPT results indicated an approximately 18 Mb deletion, which was verified by prenatal diagnosis. The chromosome microarray analysis (CMA) result showed about 19.2 Mb deletions in 21q11.2-q22.11. The karyotype analysis result showed 46,XN,del(21)(q11.2q22.1). Prenatal diagnosis was consistent with NIPT results, and the paternal karyotype revealed no obvious abnormalities., Conclusion: In this study, we successfully detected and diagnosed deletions of large fragments in chromosome 21 in a fetus using NIPT. This indicates that NIPT can provide effective genetic information for detecting fetal subchromosomal deletions/duplications., (© 2019 The Authors Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.)

Background: With the increasing availability of chromosomal microarray analysis (CMA) for congenital heart defect (CHD), genetic testing now faces new challenges due to results with uncertain clinical impact. Studies are needed to better define the penetrance of genetic variants. The aim of the study was to examine the association between CMA and CHDs in fetuses with normal karyotype., Methods: This was a retrospective study of 190 fetuses with normal karyotype that underwent CMA after a diagnosis of CHD by fetal ultrasound. Invasive prenatal diagnosis was performed between January 2015 and December 2016 at the first affiliated hospital of Air Force Medical University., Results: Chromosomal microarray analysis detected pathogenic copy number variants (pCNVs) in 13/190 (6.84%) fetuses, likely pCNVs in 5/190 (2.63%), and variants of unknown significance (VOUS) in 14/190 (7.37%). Among those with pCNVs, none (0%) yielded a normal live birth. Among those with likely pCNVs, 2/5 (40.0%) yielded a live birth. Among the fetuses with VOUS, 10/14 (71.5%) yielded a live birth., Conclusion: These results highlight the usefulness of CMA for prenatal genetic diagnosis of fetuses with CHDs and normal karyotype. In fetuses with CHD, the application of CMA could increase the detection rate of pCNVs causing CHDs. In this study, some VOUS were likely pathogenic, but additional studies are necessary to confirm these findings., (© 2018 Wiley Periodicals, Inc.)

Objectives: Cell-free fetal DNA has been widely used in prenatal genetic testing during recent years. We explored the feasibility of non-invasive prenatal testing (NIPT) for analysis of common fetal aneuploidies among pregnancies in northwest China., Material and Methods: A total of 8594 maternal blood samples were collected from October 2014 to December 2017 in the Department of Obstetrics and Gynecology at the First Affiliated Hospital of the Air Force Medical University. Cases with positive screening results by NIPT detection were validated using karyotype analysis., Results: Of 8594 clinical pregnancies, 88 had positive NIPT results and 78 of 88 (88.6%) positive NIPT results were shown to be false-positive by amniotic fluid puncture and chromosome karyotyping analysis. There were 44 cases (49.44%) with trisomy 21, 18, and 13 syndromes (30 cases of trisomy 21, 9 cases of trisomy 18, and 5 cases of trisomy 13). There were 44 cases (50.56%) with sex chromosome abnormalities, including 11 cases with Turner syndrome (45, X), 17 cases with Triple X syndrome (47, XXX), 2 cases with Klinefelter syndrome (47, XXY), and 14 cases with 47, XYY syndrome (47, XYY)., Conclusions: The accuracy, specificity, high efficiency, and acceptance of NIPT can effectively avoid birth defects and improve the quality of the birth population. We should deepen mining and analysis of the clinical data and explore ways to use NIPT. It is recommended that the NIPT guidelines be extended to low-risk patients to further explore the impact of a significant increase in screening.

Background: To offer 4-year clinical prenatal diagnosis experience of Duchenne muscular dystrophy (DMD)., Methods: Denaturing high-performance liquid chromatography (DHPLC) and Sanger sequencing were used for molecular diagnosis of 237 DMD families., Results: In the study, deletions, duplications, complex rearrangement and small mutations accounted for 47.3%, 8.4%, 1.7% and 42.6% of 237 families, respectively. Sixty-six different deletion patterns were identified in 112 families. Fourteen different duplication patterns were identified in 20 families and 4 complex rearrangements were identified. About 87.1% different small mutation patterns were identified, including 37.6% different nonsense mutation patterns, 24.8% different frameshift mutation patterns, 7.9% different missense mutation patterns, and 16.8% different splice site mutation patterns. There was no significant difference in the age of onset and mutation patterns (P > .05). The follow-up examinations revealed that the pregnancies of 14 cases were interrupted. Two cases were preterm births, 151 cases were delivered at term, 63 cases continued to pregnancy, and 7 cases were lost to follow-up., Conclusion: DHPLC and Sanger sequencing technique are efficient, sensitive, and specific in screening for DMD gene mutations. And pre-pregnancy DMD gene examination is an important step to assess mutation type of family with suspected DMD and guides exactly prenatal diagnosis in high-risk families., (© 2018 Wiley Periodicals, Inc.)

Objective: There is scant information available about fetuses with 7q11.23 copy number variants (CNVs) found during pregnancy. We studied the clinical significance of 7q11.23 CNVs in prenatal diagnosis. Materials and methods: The amniocentesis was performed on pregnant women who underwent ultrasound (US) of fetal abnormalities. After karyotype analysis, CNVs were detected using BACs-on-Beads (BoBs) technique and chromosome microarray analysis (CMA). Results: Of seven fetuses with CNV of 7q11.23, five had microdeletions and two had microduplications. Case 1 had a 7q11.23 microdeletion along with other CNVs. Case 7 was a newborn with a normal phenotype and 7q11.23 microduplication. Conclusion: The CNVs in 7q11.23 results in many clinical manifestations, but the specificity of clinical features is not high. This study demonstrated that BoBs combined with CMA allows prenatal diagnosis of CNVs involving 7q11.23, and provide a clinical basis for prenatal diagnosis and genetic counseling of such CNVs. [ABSTRACT FROM AUTHOR]