Systematic Analysis of Copy-Number Variations Associated With Early Pregnancy Loss

Wang, Y.; Li, Y.; Chen, Y.; Zhou, Ruihao; Sang, Zhiqin; Meng, Lili; Tan, Jia Hui; Qiao, Fei; Bao, Qi; Luo, Di; Peng, Chieh Yu; Wang, Y. S.; Luo, Chao; Hu, Peng; Xu, Zhouwei

doi:10.1097/01.ogx.0000669276.29328.3f

Cited by 8 publications

(17 citation statements)

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“…We found the overall prevalence of genetic variants to be significantly higher in fetuses with non-isolated CHD vs those with isolated CHD (38.6% vs 18.8%, P < 0.001). Among the genetic abnormalities, aneuploidy in particular was found to be significantly more common in fetuses with non-isolated CHD, a finding consistent with our previous work and that of others 11,19,22 . Interestingly, we did not observe a significant difference in the prevalence of CNV and sequence variants among cases with non-isolated compared with isolated fetal CHD.…”

Section: Discussionsupporting

confidence: 92%

“…Two CMA platforms were introduced for detection of aneuploidies and CNVs: the HumanCytoSNP-12 array (Illumina, San Diego, CA, USA) and the Affymetrix CytoScan 750K array (Affymetrix, Santa Clara, CA, USA). Single nucleotide polymorphism array experiments and molecular karyotype analysis were performed as reported previously 19 . CNVs were reported according to the University of California Santa Cruz (UCSC) Human Genome build 19 and the National Center for Biotechnology Information (NCBI) build 37.…”

Section: Chromosomal Microarray Analysismentioning

confidence: 99%

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Comprehensive evaluation of genetic variants using chromosomal microarray analysis and exome sequencing in fetuses with congenital heart defect

Qiao

Wang

Zhang

et al. 2021

Ultrasound in Obstet & Gyne

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What are the novel findings of this work?Using chromosomal microarray analysis (CMA) and exome sequencing in 360 unselected fetuses with congenital heart defect (CHD), positive genetic diagnoses were made in 84 (23.3%) cases, including 60 (16.7%) cases with chromosomal abnormalities detected by CMA and a further 24 (6.7%) cases with sequence variants detected by exome sequencing. The prevalence of a genetic defect was highest in fetuses with an atrioventricular septal defect (36.8%), ventricular septal defect with or without atrial septal defect (28.4%), conotruncal defect (22.2%) or right ventricular outflow tract obstruction (20.0%). We also identified two novel missense mutations and a new phenotype caused by variants in PLD1. What are the clinical implications of this work?These findings may facilitate prenatal diagnosis and provide a basis for genetic counseling in pregnancies with fetal CHD. Exome sequencing should be offered to all CHD fetuses without chromosomal abnormality or pathogenic copy number variation identified by CMA.

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Section: Discussionsupporting

confidence: 92%

Section: Chromosomal Microarray Analysismentioning

confidence: 99%

Comprehensive evaluation of genetic variants using chromosomal microarray analysis and exome sequencing in fetuses with congenital heart defect

Qiao

Wang

Zhang

et al. 2021

Ultrasound in Obstet & Gyne

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“…A recent study performing a systematic analysis of copy number variations associated with early pregnancy loss showed that 22q11.2DS was the submicroscopic imbalance most frequent in miscarriage. Therefore, it was considered to be associated with early pregnancy loss, possibly due to major cardiac malformations incompatible with pregnancy progression and development [33]. While vanishing twin was a reason for exclusion in our study, cases may be missed if the gestational sac can no longer be identified.…”

Section: Discussionmentioning

confidence: 93%

First Trimester Screening for Common Trisomies and Microdeletion 22q11.2 Syndrome Using Cell-Free DNA: A Prospective Clinical Study

Kagan¹,

Hoopmann²,

Pfaff³

et al. 2020

Fetal Diagn Ther

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Objectives: The aims of the study were to assess the falsepositive and uninformative test rate with first trimester cellfree DNA (cfDNA) screening for common trisomies and microdeletion 22q11.2 (22q11.2DS) and to examine women's attitudes toward such an approach. Methods: This is a prospective study at the Prenatal Medicine Department of the University of Tübingen, Germany, at 11-13 weeks. In all pregnancies, a detailed ultrasound examination was carried out, followed by a cfDNA analysis for common trisomies and 22q11.2DS. In cases where the cfDNA analysis indicated 22q11.2DS, invasive prenatal diagnostic testing and parental testing were performed. After delivery, a detailed neonatal clinical examination was carried out including further genetic testing. Prior to counselling about the study, we asked the pregnant women who were potentially eligible for the study to anonymously report on their knowledge about 22q11.2DS. Results: A total of 1,127 pregnancies were included in the final analysis of the study. The first cfDNA test was uninformative in 15 (1.33%) pregnancies. In 10 (0.89%) cases, the test remained uninformative, even after the second blood sample. There were 3 (0.27%) cases with a positive cfDNA test for 22q11.2DS. In all, 983 women returned the anonymous questionnaire prior to study participation. Only 80 (8.1%) women responded that they felt familiar or very familiar with 22q11.2DS. Conclusion: The addition of 22q11.2DS in first trimester cfDNA screening for common trisomies is feasible. The uninformative test rate for common trisomies and 22q11.2DS is 0.9%, and the false-positive rate for 22q11.2DS is 0.3%. Awareness and education around 22q11.2DS should be improved.

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“…24 Dai et al 25 found that the fetal chromosomal abnormality rate in firsttrimester spontaneous abortion was significantly higher than the second-trimester spontaneous abortion. Wang et al 26 reported that 309 genes were identified as potential miscarriage candidate genes by analyzing 5,003 miscarriage specimens. These studies found that chromosomal aneuploidy was one of the main genetic factors for abortion and also that some pCNVs were associated with miscarriage and stillbirth.…”

Section: Introductionmentioning

confidence: 99%

Copy number variation characterization and possible candidate genes in miscarriage and stillbirth by next‐generation sequencing analysis

Zhang

Huang

et al. 2021

The Journal of Gene Medicine

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Background: The present study aimed to explore the etiological relationship between miscarriage and stillbirth and copy number variations (CNVs), as well as provide useful genetic guidance for high-risk pregnancy.Methods: In total, 659 fetal samples were recruited and subjected to DNA extraction and CNV sequencing (CNV-seq), relevant medical records were collected.Results: There were 322 cases (48.86%) with chromosomal abnormalities, including 230 with numerical abnormalities and 92 with structural abnormalities. Chromosomal monosomy variations mainly occurred on sex chromosomes and trisomy variations mainly occurred on chromosomes 16, 22, 21, 18, 13 and 15. In total, 41 pathogenic CNVs (23 microdeletions and 18 microduplications) were detected in 27 fetal tissues.The rates of numerical chromosomal abnormalities were 29.30% (109/372), 32.39% (57/176) and 57.66% (64/111) in < 30-year-old, 30-34-year-old and ≥ 35-year-old age pregnant women, respectively, and increased with an increasing age (p < 0.001).There was statistically significant difference (χ 2 = 7.595, p = 0.022) in the rates of structural chromosomal abnormalities in these groups (13.71%, 18.75% and 7.21%, respectively). The rates of numerical chromosomal abnormalities were 45.44% (219/482), 7.80% (11/141) and 0% (0/36) in the ≤ 13 gestational weeks, 14-27 weeks and ≥ 28 weeks groups, respectively, and decreased with respect to the increasing gestational age of the fetuses (p < 0.001). Conclusions:The present study has obtained useful and accurate genetic etiology information that will provide useful genetic guidance for high-risk pregnancies.

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Systematic Analysis of Copy-Number Variations Associated With Early Pregnancy Loss

Cited by 8 publications

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Comprehensive evaluation of genetic variants using chromosomal microarray analysis and exome sequencing in fetuses with congenital heart defect

Comprehensive evaluation of genetic variants using chromosomal microarray analysis and exome sequencing in fetuses with congenital heart defect

First Trimester Screening for Common Trisomies and Microdeletion 22q11.2 Syndrome Using Cell-Free DNA: A Prospective Clinical Study

Copy number variation characterization and possible candidate genes in miscarriage and stillbirth by next‐generation sequencing analysis

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