Detection of copy number variants with chromosomal microarray in 10 377 pregnancies at a single laboratory

Lin, Yi Hui; Jong, Yiin Jeng; Huang, Pin Chia; Tsai, Chris

doi:10.1111/aogs.13886

Cited by 12 publications

(5 citation statements)

References 26 publications

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“…Wapner et al enrolled 4406 women and demonstrated an increased diagnostic rate in microarray over karyotyping of 6.0% among cases with ultrasound abnormalities and 1.7% among pregnant women with advanced maternal age or positive screening results [ 33 ]. A 2020 study indicated that the frequency of pathogenic or likely pathogenic CNVs is 1.2% in all indications by prenatal SNP array [ 34 ]. A recent review summarized a total of 29,612 cases using array techniques in foetuses with abnormal structures and the rate of pathogenic or likely pathogenic CNVs was 0.4–2.5% [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Detection rates of abnormalities in over 10,000 amniotic fluid samples at a single laboratory

Kakongoma

et al. 2023

BMC Pregnancy Childbirth

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Background A growing number of cytogenetic techniques have been used for prenatal diagnosis. This study aimed to demonstrate the usefulness of karyotyping, BACs-on-Beads (BoBs) assay and single nucleotide polymorphism (SNP) array in prenatal diagnosis during the second trimester based on our laboratory experience. Methods A total of 10,580 pregnant women with a variety of indications for amniocentesis were enrolled in this retrospective study between January 2015 and December 2020, of whom amniotic fluid samples were analysed in 10,320 women. The main technical indicators of participants in the three different technologies were summarized, and cases of chromosome abnormalities were further evaluated. Results The overall abnormality detection rate of karyotyping among all the amniotic fluid samples was 15.4%, and trisomy 21 was the most common abnormality (20.9%). The total abnormality detection rate of the BoBs assay was 5.6%, and the diagnosis rate of microdeletion/microduplication syndromes that were not identified by karyotyping was 0.2%. The detection results of the BoBs assay were 100.0% concordant with karyotyping analysis in common aneuploidies. Seventy (87.5%) cases of structural abnormalities were missed by BoBs assay. The total abnormality detection rate of the SNP array was 21.6%. The detection results of common aneuploidies were exactly the same between SNP array and karyotyping. Overall, 60.1% of structural abnormalities were missed by SNP array. The further detection rate of pathogenic significant copy number variations (CNVs) by SNP was 1.4%. Conclusions Karyotyping analysis combined with BoBs assay or SNP array for prenatal diagnosis could provide quick and accurate results. Combined use of the technologies, especially with SNP array, improved the diagnostic yield and interpretation of the results, which contributes to genetic counselling. BoBs assay or SNP array could be a useful supplement to karyotyping.

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Section: Discussionmentioning

confidence: 99%

Detection rates of abnormalities in over 10,000 amniotic fluid samples at a single laboratory

Kakongoma

et al. 2023

BMC Pregnancy Childbirth

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“…[1][2][3] Their detection, especially in prenatal diagnosis where fetal anomalies are identified, is vital for clinical decision-making and parental counseling. [3][4][5] Chromosomal microarray (CMA) has long been considered the gold standard for identifying CNVs and is widely accepted as the first tier diagnostic tool in cases of congenital anomalies Additionally, the use of single nucleotide polymorphism (SNP) arrays provides valuable genotyping information which enables the detection of copy number neutral absence of heterozygosity (AOH), which may arise from a deletion, autozygosity (identity-by-descent), or certain types of uniparental disomy (UPD)-isodisomy. However, with advancements in NGS technology, it is prudent to recognize the limitations of microarray technology and consider the benefits of NGS.…”

Section: Introductionmentioning

confidence: 99%

“…Chromosomal abnormalities including Copy Number Variants (CNVs) are a well‐recognized cause of human disease, many of which are present in prenatal and neonatal periods as fetal structural anomalies and congenital malformations 1–3 . Their detection, especially in prenatal diagnosis where fetal anomalies are identified, is vital for clinical decision‐making and parental counseling 3–5 …”

Section: Introductionmentioning

confidence: 99%

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Validation of low‐pass genome sequencing for prenatal diagnosis

Mighton,

Noor,

Watkins

et al. 2024

Prenatal Diagnosis

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ObjectiveChromosomal microarray (CMA), while considered the gold standard for detecting copy number variants (CNVs) in prenatal diagnostics, has its limitations, including the necessity to replace aging microarray equipment, low throughput, a static design, and an inefficient multi‐day workflow. This study evaluates the feasibility of low‐pass genome sequencing (LP‐GS) as a potential replacement for CMA in prenatal diagnostics.MethodsWe comprehensively compared LP‐GS at 10x and 5x average depths with CMA in a prenatal laboratory. We examined parameters, including concordance, sensitivity, specificity, workflow efficiency, and cost‐effectiveness.ResultsWe found a high degree of agreement between LP‐GS and CMA for detecting CNVs and absence of heterozygosity. Furthermore, compared to CMA, LP‐GS increased workflow efficiency and proved to be cost‐neutral at 10x and cost‐effective at 5x.ConclusionOur study suggests that LP‐GS is a promising alternative to CMA in prenatal diagnostics, offering advantages, including a more efficient workflow and scalability for larger testing volumes. Importantly, for clinical laboratories that have adopted next‐generation sequencing in a separate capacity, LP‐GS facilitates a unified NGS‐centric approach, enabling workflow consolidation. By offering a single, streamlined platform for detecting a broad range of genetic variants, LP‐GS may represent a critical step toward enhancing the diagnostic capabilities of prenatal laboratories.

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“…Previous studies showed that the yield of pCNV was 6%-7% in ultrasonography anomalous fetuses with a normal karyotype, 7,8 and 0.4%-2% in fetuses without anomalies. [9][10][11] Cardiovascular, genitourinary, skeletal, and central nervous system defects were reported to be most commonly associated with chromosomal aberrations. [12][13][14][15][16][17][18] Therefore, the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) recommend CMA as a first-tier test in the diagnostic evaluation of fetal structural abnormalities for fetuses undergoing prenatal diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Low-pass genome sequencing reveals associations between copy number variations and fetal ultrasonographic anomalies and soft markers in a cohort of 43,721 fetuses

Pan¹,

Zhang²,

Yuan³

et al. 2022

Preprint

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Objective To systematically explore the association between pathogenic/likely pathogenic copy number variations (pCNV) and ultrasonographic anomalies and soft markers. Design Retrospective cohort study. Setting Data were obtained from multiple centers in china. Population or Sample Fetuses performed low-pass genome sequencing and ultrasonography between 2016 and 2020. Method The yields of pCNV under various ultrasonographic indications were compared with that of fetuses with no identifiable anomalies. In addition, the ultrasonographic characteristics of aneuploidy and pCNV were described in comparison with those of fetuses without chromosomal aberrations. Main Outcome Measures Yields of aneuploidy and pCNV in different ultrasonographic indications. Results Ten of the 12 ultrasonographic anomalies had significantly higher yield of pCNV, except for fetal hydrops and abnormal amniotic fluid, of which the gastrointestinal, facial, respiratory systems, and abdominal wall defect were rarely reported. Similarly, five of the 12 soft markers had significantly higher yield of pCNV, with single umbilical artery being rarely reported. Furthermore, this study reported that four duplications/deletions were associated with novel ultrasonographic findings. Conclusions Based on specific ultrasonographic phenotypes, prenatal genetic testing could be considered in a tailored fashion. Keywords Low-pass genome sequencing; ultrasonographic anomaly; soft marker; copy number variations; aneuploidy; prenatal diagnosis Tweetable abstract Fetuses with structural anomalies and specific soft markers are recommended for copy number variations analysis

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Detection of copy number variants with chromosomal microarray in 10 377 pregnancies at a single laboratory

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 12 publications

References 26 publications

Detection rates of abnormalities in over 10,000 amniotic fluid samples at a single laboratory

Detection rates of abnormalities in over 10,000 amniotic fluid samples at a single laboratory

Validation of low‐pass genome sequencing for prenatal diagnosis

Low-pass genome sequencing reveals associations between copy number variations and fetal ultrasonographic anomalies and soft markers in a cohort of 43,721 fetuses

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