Analysis of Genomic Copy Number Variation in Miscarriages During Early and Middle Pregnancy

Wu, Heming; Huang, Qingyan; Zhang, Xia; Yu, Zhikang; Zhong, Zhixiong

doi:10.3389/fgene.2021.732419

Cited by 18 publications

(28 citation statements)

References 72 publications

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“…In the present study, the chromosomal structural abnormality rate (6.8%, 18/264) of miscarriage samples in AMA was lower than that (12.6%, 113/896) of miscarriage samples in YMA, which is in line with a previous research [14], because the frequency of embryotic chromosomal structural abnormalities did not seem to be correlated with AMA [14,48]. A larger population study is needed to further clarify the noncorrelation.…”

Section: The Associations Between Chromosomal Abnormalities Of Cvss A...supporting

confidence: 88%

“…In this study, all 449 and 711 CVSs were successfully examined via CNV-seq and SNP array, respectively, thus, the detection success rate of both methods was 100%. The overall rate of chromosomal abnormalities was 65% (754/1160), which is slightly higher than the reported rates in previous researches [14,31,32] (Table 2). The chromosomal abnormality detection rates were 58.4% (415/711) and 75.5% (339/449), for CMA and CNV-seq, respectively, and the difference in the abnormality rates detected by the two methods was statistically signi cant (p < 0.001).…”

Section: The Associations Between Chromosomal Abnormalities Of Cvss A...contrasting

confidence: 60%

“…Recently, CNV-seq is gradually being used in detecting the genetic causes of CVSs [14,27,28]. Both molecular karyotyping technologies do not require cell culture and are reliable in detecting CNVs.…”

Section: The Associations Between Chromosomal Abnormalities Of Cvss A...mentioning

confidence: 99%

“…The number of reads after sample quality control is more than 8M Sequence depth is ~0.1x. Burrows-Wheeler algorithm for calculating CNV was performed according to the previous study [14]. Data were analyzed using the human genome hg19 reference sequence.…”

Section: Cnv Sequencingmentioning

confidence: 99%

“…It is well known that segmental deletion and/or duplication can cause miscarriage. Additionally, submicroscopic pathogenic CNVs (pCNVs) are the second-highest aberrations identi ed in products of conception [10][11][12][13][14][15]. However, speci c data regarding the association between submicroscopic CNVs and spontaneous miscarriage is still limited.…”

Section: Introductionmentioning

confidence: 99%

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Chromosomal copy-number variation analysis of villous tissues using molecular karyotyping in early missed abortions

Xue

Guo

et al. 2022

Preprint

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Karyotype abnormalities are the most common etiology of early spontaneous miscarriage. However, traditional karyotyping of chorionic villus samples (CVSs) is limited by cell culture and its low resolution. The objective of our study was to investigate the efficiency of molecular karyotyping technology in detecting the CNVs of early missed abortion tissues. Chromosome analysis of 1160 abortion CVSs in early pregnancy, collected by hysterosuction, was conducted in Fujian, China, with informed consent secured from the participants; 449 chromosomal CNV analyses were conducted via CNV-seq and 711 analyses were conducted using microarray. Clinically submicroscopic CNVs of abortion villous tissues were identified to clarify the cause of the abortion and to guide the participants’ subsequent pregnancies. Among the 1160 samples, 754 cases (65.0%) with genetic abnormalities were identified, of which, 531 (45.8%) were single aneuploidies, 31 (2.7%) were multiple aneuploidies, 50 (4.3%) were polyploidies, 53 (4.6%) were partial aneuploidies, 78 (6.7%) had a microdeletion or microduplication, and 8 cases (0.7%) were uniparental disomies. However, compared with the young maternal age group, the embryotic numerical and structural chromosomal rate was significantly different in the advanced maternal age group, while there was no significant positive correlation between maternal age and other types of genetic abnormalities. A higher detection rate of embryotic chromosomal abnormalities, especially submicroscopic CNVs, was achieved using CNV-seq and microarray. Our results indicate that embryonic CNVs cause early miscarriage and highlight the importance of CNV analysis in CVSs, irrespective of maternal age.

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Section: The Associations Between Chromosomal Abnormalities Of Cvss A...supporting

confidence: 88%

Section: The Associations Between Chromosomal Abnormalities Of Cvss A...contrasting

confidence: 60%

Section: The Associations Between Chromosomal Abnormalities Of Cvss A...mentioning

confidence: 99%

Section: Cnv Sequencingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chromosomal copy-number variation analysis of villous tissues using molecular karyotyping in early missed abortions

Xue

Guo

et al. 2022

Preprint

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Sequential application of copy number variation sequencing and quantitative fluorescence polymerase chain reaction in genetic analysis of miscarriage and stillbirth

Chen

Zhang

et al. 2023

Molec Gen & Gen Med

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BackgroundCopy number variation sequencing (CNV‐seq) could detect most chromosomal abnormalities except polyploidy, and quantitative fluorescence polymerase chain reaction (QF‐PCR) is a supplementary method to CNV‐seq in triploid detection. This study aimed to evaluate the feasibility of sequential application of CNV‐seq and QF‐PCR in genetic analysis of miscarriage and stillbirth.MethodsA total of 261 fetal specimens were analyzed by CNV‐seq, and QF‐PCR was only further performed for samples with normal female karyotype identified by CNV‐seq. Cost and turnaround time (TAT) was analyzed for sequential detection strategy. Subgroup analysis and logistic regression were carried out to evaluate the relationship between clinical characteristics (maternal age, gestational age, and number of pregnancy losses) and the occurrence of chromosomal abnormalities.ResultsAbnormal results were obtained in 120 of 261 (45.98%) cases. Aneuploidy was the most common abnormality (37.55%), followed by triploidy (4.98%) and pathogenic copy number variations (pCNVs) (3.45%). CNV‐seq could detect the triploidy with male karyotype, and QF‐PCR could further identify the remaining triploidy with female karyotype. In this study, we found more male triploidies than female triploidies. With the same ability in chromosomal abnormalities detection, the cost of sequential strategy decreased by 17.35% compared with combined strategy. In subgroup analysis, significant difference was found in the frequency of total chromosomal abnormalities between early abortion group and late abortion group. Results of logistic regression showed a trend that pregnant women with advanced age, first‐time abortion, and abortion earlier than 12 weeks were more likely to detect chromosomal aberrations in their products of conception.ConclusionSequential application of CNV‐seq and QF‐PCR is an economic and practical strategy to identify chromosomal abnormalities in fetal tissue.

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Exposure to endogenous and exogenous sex hormones and reproductive history influence prognosis in women with ALS

et al. 2023

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Introduction/AimsAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a higher incidence in men suggesting an influence of sex steroids. Our objective was to investigate past exposure to endogenous and synthetic steroids in female ALS patients and controls.MethodsWe administered a questionnaire to 158 postmenopausal women (75 ALS patients and 83 controls). We calculated reproductive time span (RTS), lifetime endogenous estrogen (LEE) and progesterone exposures (LPE), oral contraceptive pill (OCP) use, and reproductive history.ResultsALS patients showed shorter LEE and LPE, a lower proportion of breast cancer, and 11% showed no history of pregnancies vs. 4% of controls. Odds ratios (ORs) showed that <17 y of LEE and a delayed menarche (>13 y) constitute risk factors for ALS [OR = 2.1 (95% confidence interval {CI}, 1.08–4.2); and OR = 2.4 (95% CI, 1.1–5.1) respectively]. According to Cox survival analysis, for each year the LEE increased over 17 y, it was independently associated with longer survival [hazard ratio (HR) = 0.37 (95% CI, 0.16–0.85)] after adjusting for smoking, age and site of onset. Multivariate regression analysis demonstrated that for each month using OCP for longer than 40 mo increased the risk of ALS [adjusted OR = 4.1 (95% CI, 1.2–13.8)].DiscussionThus, longer exposure to endogenous female sex steroids increased survival and reduced ALS susceptibility. In contrast, longer exposure to synthetic sex steroids showed a negative impact by reducing the production of endogenous female sex steroids or due to crossover with other steroid receptors. Given the neuroprotective effects of sex steroids, we suggest that abnormalities of neuroendocrine components may alter motor function in women with ALS.

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Analysis of Genomic Copy Number Variation in Miscarriages During Early and Middle Pregnancy

Cited by 18 publications

References 72 publications

Chromosomal copy-number variation analysis of villous tissues using molecular karyotyping in early missed abortions

Chromosomal copy-number variation analysis of villous tissues using molecular karyotyping in early missed abortions

Sequential application of copy number variation sequencing and quantitative fluorescence polymerase chain reaction in genetic analysis of miscarriage and stillbirth

Exposure to endogenous and exogenous sex hormones and reproductive history influence prognosis in women with ALS

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