scholarly journals Chromosomal variants accumulate in genomes of the spontaneous aborted fetuses revealed by chromosomal microarray analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259518
Author(s):  
Sen Li ◽  
Lei-Ling Chen ◽  
Xing-Hua Wang ◽  
Hai-Jing Zhu ◽  
Xiao-Long Li ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Microarray Data ◽  
Copy Number Variations ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Success Rates ◽  
Male Patients ◽  
Relationship Of ◽  
The Relationship ◽  
Genome Variants

Spontaneous abortion is an impeding factor for the success rates of human assistant reproductive technology (ART). Causes of spontaneous abortion include not only the pregnant mothers’ health conditions and lifestyle habits, but also the fetal development potential. Evidences had shown that fetal chromosome aneuploidy is associated with fetal spontaneous abortion, however, it is still not definite that whether other genome variants, like copy number variations (CNVs) or loss of heterozygosity (LOHs) is associated with the spontaneous abortion. To assess the relationship between the fetal genome variants and abortion during ART, a chromosomal microarray data including chromosomal information of 184 spontaneous aborted fetuses, 147 adult female patients and 78 adult male patients during ART were collected. We firstly analyzed the relationship of fetal aneuploidy with maternal ages and then compared the numbers and lengths of CNVs (< 4Mbp) and LOHs among adults and aborted fetuses. In addition to the already known association between chromosomal aneuploidy and maternal ages, from the chromosomal microarray data we found that the numbers and the accumulated lengths of short CNVs and LOHs in the aborted fetuses were significantly larger or longer than those in adults. Our findings indicated that the increased numbers and accumulated lengths of CNVs or LOHs might be associated with the spontaneous abortion during ART.

scholarly journals Anti-Mullerian hormone (AMH) as predictor of ovarian reserve

2017 ◽  
Vol 6 (9) ◽  
pp. 4006 ◽  
Author(s):  
Chaitanya Ashok Shembekar ◽  
Jayshree Jayant Upadhye ◽  
Manisha Chaitanya Shembekar ◽  
Shravani H. Welekar
Keyword(s):  
Ovarian Response ◽  
Poor Responders ◽  
Success Rates ◽  
Antral Follicles ◽  
Relationship Of ◽  
The Relationship ◽  
High Chance ◽  
Antagonist Protocol ◽  
High Range

Background: Anti-Müllerian hormone (AMH) is produced by the granulosa cells of preantral and small antral follicles and its levels can be assessed in serum. Since the number of ovarian follicles declines with increasing age, AMH levels might be used as a marker for ovarian ageing. Therefore, we studied the relationship between AMH levels and ovarian response during ovarian stimulation for In vitro fertilization.Methods: A total of 100 patients who have undergone their ICSI treatment cycle using a GnRH antagonist protocol were retrospectively included. Co-relation between AMH and antral follicular count (AFC) was assessed.Results: In present study, 36% patients had normal AMH, 18% patients were in low normal range, 5% patients had low values and 2% patients had very low values. 41% of patients had values in high range suggestive of PCOS. Amongst this, 21% had values between 4 to 8 ng/ml where we got good AFC count and good result in terms of pregnancy. 80% were good responders while 20% were poor responders. When we evaluated the relationship of retrieved oocyte counts with the parameters included, we found that only basal AMH levels and the number of antral follicles were statistically correlated.Conclusions: High AMH levels correlated with low cancellation rates, retrieval of more eggs, higher live birth rates and a high chance for freezing of embryos. Low AMH levels (alone) do not predict low success rates in women under 35 years of age.

scholarly journals Diagnostic accuracy and value of chromosomal microarray analysis for chromosomal abnormalities in prenatal detection: a prospective clinical study

2020 ◽  
Author(s):  
Hailong Huang ◽  
Yan Wang ◽  
Min Zhang ◽  
Na Lin ◽  
Gang An ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Microarray Analysis ◽  
Operating Characteristic ◽  
Chromosomal Abnormalities ◽  
Area Under The Curve ◽  
Diagnostic Value ◽  
Chromosomal Microarray ◽  
Prospective Clinical Study ◽  
Chromosomal Microarray Analysis ◽  
Success Rates

Abstract Background Chromosomal microarray analysis (CMA) has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. The aim of this study was to compare the accuracy and diagnostic value of CMA and karyotyping on chromosomal abnormalities in Fujian province of South China. Methods In the study, 410 samples were obtained from pregnant women between March 2015 and December 2016, including 3 villus (0.73%, 3/410), 296 amniotic fluid (72.20%, 296/410), and 111 umbilical cord blood (27.07%, 111/410). Each sample was screening for chromosomal abnormalities by both using CMA and karyotyping. Results The success rates of CMA and karyotyping were 100% (410/410) and 99.27% (407/410), respectively. 61 (14.88%, 61/410) samples were presented with chromosomal abnormalities using CMA, whereas 47 (11.46%, 47/410) samples were shown with chromosomal abnormalities using karyotyping. 31 (7.56%, 31/410) samples with normal karyotypes were found to have chromosomal abnormalities using CMA. Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of CMA on the diagnosis of chromosomal abnormalities was 0.93, with 90.68% sensitivity and 94.40% specificity. The AUC of karyotyping on the diagnosis of chromosomal abnormalities was 0.90, with 87.56% sensitivity and 91.22% specificity. Conclusions Our data demonstrated that CMA has a better diagnostic value for screening chromosomal abnormalities, especially for pregnant women with normal karyotypes.

scholarly journals Comprehensive Evaluation of Non-invasive Prenatal Screening to Detect Fetal Copy Number Variations

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Wang ◽  
Bin Zhang ◽  
Lingna Zhou ◽  
Qin Zhou ◽  
Yingping Chen ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Pregnant Women ◽  
Copy Number ◽  
Prenatal Screening ◽  
Comprehensive Evaluation ◽  
Copy Number Variations ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Non Invasive ◽  
Pathogenic Cnvs

ObjectiveTo evaluate the effectiveness of non-invasive prenatal screening (NIPS) in prenatal screening of fetal pathogenic copy number variants (CNVs).Materials and MethodsWe evaluated the prenatal screening capacity using traditional and retrospective approaches. For the traditional method, we evaluated 24,613 pregnant women who underwent NIPS; cases which fetal CNVs were suggested underwent prenatal diagnosis with chromosomal microarray analysis (CMA). For the retrospective method, we retrospectively evaluated 47 cases with fetal pathogenic CNVs by NIPS. A systematic literature search was performed to compare the evaluation efficiency.ResultsAmong the 24,613 pregnant women who received NIPS, 124 (0.50%) were suspected to have fetal CNVs. Of these, 66 women underwent prenatal diagnosis with CMA and 13 had true-positive results. The positive predictive value (PPV) of NIPS for fetal CNVs was 19.7%. Among 1,161 women who did not receive NIPS and underwent prenatal diagnosis by CMA, 47 were confirmed to have fetal pathogenic CNVs. Retesting with NIPS indicated that 24 of these 47 cases could also be detected by NIPS, representing a detection rate (DR) of 51.1%. In total, 10 publications, namely, six retrospective studies and four prospective studies, met our criteria and were selected for a detailed full-text review. The reported DRs were 61.10–97.70% and the PPVs were 36.11–80.56%. The sizes of CNVs were closely related to the accuracy of NIPS detection. The DR was 41.9% (13/31) in fetuses with CNVs ≤ 3 Mb, but was 55.0% (11/20) in fetuses with CNVs &gt; 3 Mb. Finally, to intuitively show the CNVs accurately detected by NIPS, we mapped all CNVs to chromosomes according to their location, size, and characteristics. NIPS detected fetal CNVs in 2q13 and 4q35.ConclusionThe DR and PPV of NIPS for fetal CNVs were approximately 51.1% and 19.7%, respectively. Follow-up molecular prenatal diagnosis is recommended in cases where NIPS suggests fetal CNVs.

scholarly journals Carbohydrate antigen-125, calcium, and hemoglobin as predictive clinical indicator for ocular metastasis in male liver cancer patients

2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Qian-Hui Xu ◽  
Pei-Wen Zhu ◽  
Biao Li ◽  
Wen-Qing Shi ◽  
Qi Lin ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Primary Liver Cancer ◽  
Carbohydrate Antigen ◽  
Serum Biomarkers ◽  
Ca 125 ◽  
Carbohydrate Antigen 125 ◽  
Male Patients ◽  
Ocular Metastasis ◽  
Relationship Of ◽  
The Relationship

Abstract Background Primary liver cancer (PLC) is a common type of cancer among men worldwide. Little is known regarding the relationship of liver cancer with ocular metastasis (OM). Drinking has been also reported to be related not only to the occurrence of liver cancer but also to the causes of some ocular lesions. Purpose A diagnostic standard for the levels of serum biomarkers associated with OM derived from liver cancer in men is urgently needed. Material and methods We examined the association between OM in liver cancer and its serum biomarkers. A total of 1254 male patients with liver cancer were recruited in this retrospective study between July 2002 and December 2012. We assessed the relationship between drinking preference and OM in male patients with liver cancer, and aimed to identify an independent prognostic factor or establish a quantitative indicator for OM. Results By assessing the potential indicators, carbohydrate antigen-125 (CA-125), calcium, and hemoglobin (Hb) were found to be most valuable in the diagnosis of OM in male patients with liver cancer. Conclusion CA-125, calcium, and Hb are independent risk factors of OM in patients with liver cancer who consume alcohol.

scholarly journals Application of Chromosome Microarray Analysis in the Investigation of Developmental Disabilities and Congenital Anomalies: Single Center Experience and Review of NRXN3 and NEDD4L Deletions

2020 ◽  
Vol 11 (4) ◽  
pp. 197-206
Author(s):  
Alper Han Çebi ◽  
Şule Altıner
Keyword(s):  
Developmental Disabilities ◽  
Microarray Analysis ◽  
Congenital Anomalies ◽  
Copy Number Variations ◽  
Step Test ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Multiple Congenital Anomalies ◽  
Single Center Experience ◽  
Genome Wide

Chromosomal microarray analysis (CMA) is a first step test used for the diagnosis of patients with developmental delay, intellectual disability, autistic spectrum disorder, and multiple congenital anomalies. Its widespread usage has allowed genome-wide identification of copy number variations (CNVs). In our study, we performed a retrospective study on clinical and microarray data of 237 patients with developmental disabilities and/or multiple congenital anomalies and investigated the clinical utility of CMA. Phenotype-associated CNVs were detected in 15.18% of patients. Besides, we detected submicroscopic losses on 14q24.3q31.1 in a patient with speech delay and on 18q21.31q21.32 in twin patients with seizures. Deletions of <i>NRXN3</i> and <i>NEDD4L</i> were responsible for the phenotypes, respectively. This study showed that CMA is a powerful diagnostic tool in this patient group and expands the genotype-phenotype correlations on developmental disabilities.

scholarly journals Simultaneous Detection of CNVs and SNVs Improves the Diagnostic Yield of Fetuses with Ultrasound Anomalies and Normal Karyotypes

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1397
Author(s):  
Qingwei Qi ◽  
Yulin Jiang ◽  
Xiya Zhou ◽  
Hua Meng ◽  
Na Hao ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Diagnostic Yield ◽  
Simultaneous Detection ◽  
Genetic Diagnosis ◽  
Copy Number Variations ◽  
Molecular Diagnostic ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Single Nucleotide Variants ◽  
Sequential Approach

The routine assessment to determine the genetic etiology for fetal ultrasound anomalies follows a sequential approach, which usually takes about 6–8 weeks turnaround time (TAT). We evaluated the clinical utility of simultaneous detection of copy number variations (CNVs) and single nucleotide variants (SNVs)/small insertion-deletions (indels) in fetuses with a normal karyotype with ultrasound anomalies. We performed CNV detection by chromosomal microarray analysis (CMA) or low pass CNV-sequencing (CNV-seq), and in parallel SNVs/indels detection by trio-based clinical exome sequencing (CES) or whole exome sequencing (WES). Eight-three singleton pregnancies with a normal fetal karyotype were enrolled in this prospective observational study. Pathogenic or likely pathogenic variations were identified in 30 cases (CNVs in 3 cases, SNVs/indels in 27 cases), indicating an overall molecular diagnostic rate of 36.1% (30/83). Two cases had both a CNV of uncertain significance (VOUS) and likely pathogenic SNV, and one case carried both a VOUS CNV and an SNV. We demonstrated that simultaneous analysis of CNVs and SNVs/indels can improve the diagnostic yield of prenatal diagnosis with shortened reporting time, namely, 2–3 weeks. Due to the relatively long TAT for sequential procedure for prenatal genetic diagnosis, as well as recent sequencing technology advancements, it is clinically necessary to consider the simultaneous evaluation of CNVs and SNVs/indels to enhance the diagnostic yield and timely TAT, especially for cases in the late second trimester or third trimester.

scholarly journals High Detection Rate of Copy Number Variations Using Capture Sequencing Data: A Retrospective Study

2020 ◽  
Vol 66 (3) ◽  
pp. 455-462 ◽  
Author(s):  
Yu Sun ◽  
Xiantao Ye ◽  
Yanjie Fan ◽  
Lili Wang ◽  
Xiaomei Luo ◽  
...  
Keyword(s):  
Copy Number ◽  
Diagnostic Yield ◽  
Copy Number Variations ◽  
Systematic Evaluation ◽  
High Yield ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Large Sample Size ◽  
Analytical Sensitivity ◽  
Capture Sequencing

Abstract Background Capture sequencing (CS) is widely applied to detect small genetic variations such as single nucleotide variants or indels. Algorithms based on depth comparison are becoming available for detecting copy number variation (CNV) from CS data. However, a systematic evaluation with a large sample size has not been conducted to evaluate the efficacy of CS-based CNV detection in clinical diagnosis. Methods We retrospectively studied 3010 samples referred to our diagnostic laboratory for CS testing. We used 68 chromosomal microarray analysis–positive samples (true set [TS]) and 1520 reference samples to build a robust CS-CNV pipeline. The pipeline was used to detect candidate clinically relevant CNVs in 1422 undiagnosed samples (undiagnosed set [UDS]). The candidate CNVs were confirmed by an alternative method. Results The CS-CNV pipeline detected 78 of 79 clinically relevant CNVs in TS samples, with analytical sensitivity of 98.7% and positive predictive value of 49.4%. Candidate clinically relevant CNVs were identified in 106 UDS samples. CNVs were confirmed in 96 patients (90.6%). The diagnostic yield was 6.8%. The molecular etiology includes aneuploid (n = 7), microdeletion/microduplication syndrome (n = 40), and Mendelian disorders (n = 49). Conclusions These findings demonstrate the high yield of CS-based CNV. With further improvement of our CS-CNV pipeline, the method may have clinical utility for simultaneous evaluation of CNVs and small variations in samples referred for pre- or postnatal analysis.

Rapid Diagnosis of Imprinting Disorders Involving Copy Number Variation and Uniparental Disomy Using Genome-Wide SNP Microarrays

2015 ◽  
Vol 146 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Weiqiang Liu ◽  
Rui Zhang ◽  
Jun Wei ◽  
Huimin Zhang ◽  
Guojiu Yu ◽  
...  
Keyword(s):  
Copy Number ◽  
Snp Array ◽  
Uniparental Disomy ◽  
Copy Number Variations ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Imprinting Disorders ◽  
Genome Wide ◽  
Number Variation ◽  
Efficient Alternative

Imprinting disorders, such as Beckwith-Wiedemann syndrome (BWS), Prader-Willi syndrome (PWS) and Angelman syndrome (AS), can be detected via methylation analysis, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), or other methods. In this study, we applied single nucleotide polymorphism (SNP)-based chromosomal microarray analysis to detect copy number variations (CNVs) and uniparental disomy (UPD) events in patients with suspected imprinting disorders. Of 4 patients, 2 had a 5.25-Mb microdeletion in the 15q11.2q13.2 region, 1 had a 38.4-Mb mosaic UPD in the 11p15.4 region, and 1 had a 60-Mb detectable UPD between regions 14q13.2 and 14q32.13. Although the 14q32.2 region was classified as normal by SNP array for the 14q13 UPD patient, it turned out to be a heterodisomic UPD by short tandem repeat marker analysis. MS-MLPA analysis was performed to validate the variations. In conclusion, SNP-based microarray is an efficient alternative method for quickly and precisely diagnosing PWS, AS, BWS, and other imprinted gene-associated disorders when considering aberrations due to CNVs and most types of UPD.

scholarly journals Relationship between Clinical Parameters and Chromosomal Microarray Data in Infants with Developmental Delay

Healthcare ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 305
Author(s):  
Zeeihn Lee ◽  
Byung Joo Lee ◽  
Sungwon Park ◽  
Donghwi Park
Keyword(s):  
Developmental Delay ◽  
Diagnostic Yield ◽  
Copy Number Variations ◽  
Gene Copy ◽  
Chromosomal Microarray ◽  
Clinical Parameters ◽  
Brain Anomalies ◽  
Pathogenic Cnvs ◽  
Clinical Records ◽  
The Relationship

Chromosomal microarray (CMA) is considered a first-tier test for genetic analysis as it can be used to examine gene copy number variations (CNVs) throughout the entire genome, with enhanced sensitivity for detecting submicroscopic deletions and duplications. However, its cost can represent a heavy burden. Moreover, the diagnostic yield of CMA in infants with developmental delay (DD) was reported to be less than 10%. Therefore, we aimed to investigate the relationship between CMA results and clinical features and risk factors of DD. The study included 59 infants with DD who were recruited between August 2019 and February 2020 during a visit to the outpatient clinic of a rehabilitation department. We reviewed the clinical records of the infants regarding gender, age, body weight at birth, delivery method, brain imaging data, perinatal history, and parent-related clinical parameters, such as mother and father age at birth. The infants were categorized according to CMA results, and differences in clinical parameters were evaluated. Except for brain anomalies, there was no statistically significant differences between infants who had pathogenic and variants of unknown significance (VOUS)-likely pathogenic CNVs groups compared with those within the VOUS-likely no sub-classification, VOUS-likely benign, benign, and normal CNVs groups. The incidence of brain anomalies was significantly higher within infants with pathogenic and VOUS-likely pathogenic CNVs groups (p < 0.05). Our study suggests that infants with DD who present dysmorphism or brain anomaly may benefit from early CMA analysis, for adequate diagnosis and timely treatment. Further studies are warranted to confirm the relationship between DD clinical parameters and CMA results.

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