Integrated CNV-seq, Karyotyping and SNP-array Analyses for Effective Prenatal Diagnosis of Chromosomal Mosaicism

Ma, Na; Xi, Hui; Chen, Jing; Peng, Ying; Jia, Zhengjun; Yang, Shunli; Hu, Junfeng; Pang, Jialun; Zhang, Yalan; Hu, Rong; Wang, Hua; Liu, Jing

doi:10.21203/rs.3.rs-80004/v1

Cited by 2 publications

(4 citation statements)

References 23 publications

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“…It has been suggested that the difference in cell proliferation with various karyotypes might lead to inconsistencies between cultured samples (karyotyping) and uncultured samples (SNP array) under in vitro cell culture. Cell culture, reported to increase with the age of the culture, tended to promote the growth of euploid cells rather than aneuploid cells [ 39 ].…”

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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“…As for the deletion of 2p21 7q32.3 6q25.1 17p13.3 and4p16.3 in this series, prenatal diagnosis of this syndrome in association with abnormal ultrasonographic features has been reported little, and we considered them to be incidental ndings. CNV-seq can detect structural abnormalities larger than 100 kb and mosaicism as low as 5% [13]. The karyotype of case 12 showed a mosaic monosomy of chromosome X with a ratio of 61% (45, X [61%]/46, XX [39%]).…”

Section: Discussionmentioning

confidence: 99%

“…Chromosome microarray analysis (CMA) studies are gradually replacing traditional karyotype analysis in prenatal setting and can detect submicroscopic copy number variations (CNV) [13]. However, its high cost and low throughput limit its large-scale application in prenatal diagnosis.…”

Section: Introductionmentioning

confidence: 99%

“…Due to its high resolution, high throughput, and relatively low cost, the genome copy number variation sequencing (CNV-seq) technology based on next generation sequencing (NGS) has been gradually developed. The diagnostic yield of CNV-seq testing in foetuses with SUA has been previously estimated rarely and the studies were quite limited due to small sample size [11][12][13]. The diagnostic yield and clinical utility of CNV-seq in prenatal cases of SUA remained to be determined [14].…”

Section: Introductionmentioning

confidence: 99%

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Prenatal evaluation of chromosomal abnormalities and copy number variations in fetuses with single umbilical artery

Han

Feng

Meng

2022

Preprint

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Background A normal umbilical cord has a single umbilical vein and two umbilical arteries. Single umbilical artery (SUA) is one of the most common umbilical anomaly detected by prenatal ultrasonography. The objective of this study was to evaluate the usefulness of copy number variation sequencing (CNV-seq) and standard karyotyping in fetuses with single umbilical artery (SUA) and to investigate the genetic etiology of prenatal SUA. Methods Data from pregnancies referred for invasive testing and copy number variation sequencing (CNV-seq) due to sonographic diagnosis of fetal with SUA from 2013 to 2022 were obtained retrospectively from the computerized database. The rates of chromosome aberrations and abnormal CNV-seq findings for isolated SUA, SUA accompanied with soft markers and ultrasound malformations were calculated. Results Of the 474 fetuses with SUA that underwent karyotyping, chromosomal abnormalities were detected in fetuses, with a chromosomal abnormality rate of 10.3% (49/474). The use of CNV-seq provides a 10.2% (18/177) incremental yield of detecting pathogenic CNVs in fetuses with SUA and normal karyotype. our study showed that the risk of pathogenic chromosomal abnormalities and copy number variations were increased in the SUA combined malformation or soft markers group compared to that in the isolated SUA group.Meanwhile, fetuses with isolated SUA had an additional 3.4% (6/177) of pathogenic CNVs on top of chromosome aneuploidies. Conclusion CNV-seq could aid in the risk assessment and genetic counseling in fetuses with isolated SUA, Integrating CNV analysis and karyotyping for prenatal diagnosis of SUA in prenatal diagnosis can provide more accurate genetic proof for prenatal counseling and prediction of fetal outcomes.

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Integrated CNV-seq, Karyotyping and SNP-array Analyses for Effective Prenatal Diagnosis of Chromosomal Mosaicism

Cited by 2 publications

References 23 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

Prenatal evaluation of chromosomal abnormalities and copy number variations in fetuses with single umbilical artery

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