Dilemmas in Prenatal Chromosomal Diagnosis Revealed Through a Single Center's 30 Years' Experience and 90,000 Cases

2015 ◽  
Vol 38 (3) ◽  
pp. 218-232 ◽  
Author(s):  
Christopher Konialis ◽  
Constantinos Pangalos ◽  
. InterGenetics
Keyword(s):  
Detection Rate ◽  
Chromosomal Abnormalities ◽  
Diagnostic Yield ◽  
Prenatal Testing ◽  
Minimal Invasive ◽  
Molecular Diagnostic ◽  
Comparative Genomic ◽  
High Detection Rate ◽  
Molecular Approaches ◽  
The One

Introduction: The aim of this article is to provide a perspective of prenatal chromosomal diagnosis (PCD) derived from a single center's evolving experience from ∼90,000 consecutive prenatal cases and to highlight important issues and current dilemmas. Materials and Methods: Prenatal cases in this study (1985-2013) were referred for various indications, and PCD was performed by standard karyotype in 84,255 cases, multiplex ligation-dependent probe amplification (MLPA) panel in 3,010 cases and standalone array comparative genomic hybridization (aCGH) in 3,122 cases. Results: Classic karyotype revealed 1.7 and 7.9% of pathological cases in amniotic fluid and CVS samples, respectively, with common aneuploidies accounting for 59.6 and 64.3% of the total abnormal. Molecular approaches increased the diagnostic yield by 0.6% for MLPA and 1.6% for aCGH, uncovering pathogenic chromosomal abnormalities undetectable by karyotype analysis. Conclusions: Current molecular diagnostic capabilities and the recent introduction of noninvasive prenatal testing (NIPT) point to one current major dilemma in PCD, with serious implications in genetic counseling, relating on the one hand to reaping the benefits from the high detection rate afforded through aCGH but accepting an invasive risk, and on the other hand, offering a lower detection rate practically only for Down syndrome, with minimal invasive risk.

scholarly journals A placental trisomy 2 detected by NIPT evolved in a fetal small Supernumerary Marker Chromosome (sSMC).

2021 ◽  
Author(s):  
Justyna Anna Domaradzka ◽  
Marta Deperas ◽  
Ewa Obersztyn ◽  
Anna Kucińska-Chahwan ◽  
Nathalie Brison ◽  
...  
Keyword(s):  
Cell Line ◽  
Chromosomal Abnormalities ◽  
Marker Chromosome ◽  
Prenatal Testing ◽  
Comparative Genomic ◽  
Chromosome 2 ◽  
Non Invasive ◽  
Small Supernumerary Marker Chromosome ◽  
A Cell ◽  
Cytogenetic Analyses

Abstract Background: Non-invasive prenatal testing (NIPT) is a rapidly developing and widely used method in the prenatal screening. Recently, the widespread use of the NIPT caused a neglecting of the limitations of this technology. Case presentation: The 38-year-old woman underwent amniocentesis because of a high risk of trisomy 2 revealed by the genome-wide Non-Invasive Prenatal Test (NIPT). The invasive prenatal diagnosis revealed the mosaicism for a small supernumerary marker chromosome sSMC derived from chromosome 2. Interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes revealed three signals of centromere 2 in 30% of the cells. GTG-banded metaphases revealed abnormal karyotype (47,XX,+mar[21]/46,XX[19]) and was confirmed by array comparative genomic hybridization (aCGH). Cytogenetic analyses (FISH, aCGH, karyotype) on fetal skin biopsies were performed and confirmed the genomic gain of the centromeric region of chromosome 2. In the placenta, three cell lines were detected: a normal cell line, a cell line with trisomy 2 and a third one with only the sSMC.Conclusion: Whole-genome Non-Invasive Prenatal Testing allows not only the identification of common fetal trisomies but also diagnosis of rare chromosomal abnormalities. Especially in such cases, it is extremely important to perform not only NIPT verification on a sample of material other than trophoblast, but also to apply appropriate research methods. Such conduct allows detailed analysis of the detected aberration, thus appropriate clinical validity.

scholarly journals Application of the BACs-on-Beads assay for the prenatal diagnosis of chromosomal abnormalities in Quanzhou, China

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jianlong Zhuang ◽  
Chunnuan Chen ◽  
Yuying Jiang ◽  
Qi Luo ◽  
Shuhong Zeng ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
High Risk ◽  
Chromosomal Abnormalities ◽  
Karyotype Analysis ◽  
Prenatal Testing ◽  
High Risk Group ◽  
Success Rates ◽  
High Detection Rate ◽  
High Risk Factors ◽  
Initial Objective

Abstract Background An increasing number of techniques have been used for prenatal diagnosis of genetic abnormalities. Our initial objective was to explore the value of the BACs-on-Beads (BoBs) assay for the prenatal diagnosis of aneuploidies and microdeletion/microduplication syndromes in Quanzhou, Southeast China. Methods A total of 1409 pregnant women with high-risk factors for chromosomal abnormalities admitted to Quanzhou Women’s and Children’s Hospital were enrolled in this study. BoBs assays and karyotype analyses were conducted for all subjects. Subsequently, chromosome microarray analysis (CMA) or fluorescence in situ hybridization (FISH) was performed to validate the findings. Results In this study, karyotype analysis and BoBs assay failed in 4 cases, and 2 cases, respectively. A total of 1403 cases were successfully analyzed, with success rates of 99.72% (1405/1409) and 99.85% (1407/1409) for karyotype analysis and Bobs assay, respectively. BoBs assay rapidly detected chromosomal aneuploidies in line with the karyotyping data. Additionally, 23 cases of microdeletions/microduplications were detected by BoBs assay but missed by karyotyping, including 22q11.2 microdeletions/microduplications, 5p15.32p15.33 microdeletion, Xp22.31 microdeletions/microduplications, Xq27.3 microdeletion, and Yp11.2 and Yq11.22q11.222 microduplication. In comparison with karyotyping, fewer mosaicisms were identified by BoBs assay. A high detection rate of chromosomal abnormalities was observed in the high-risk group during noninvasive prenatal testing (NIPT) (41.72%) and the abnormal ultrasound group (13.43%). Conclusions BoBs assay can be used for the rapid and efficient prenatal diagnosis of common aneuploidies and microdeletion/microduplication syndromes. Moreover, the combined use of BoBs assay and karyotyping in prenatal diagnosis may allow for a more effective detection of chromosomal abnormalities.

scholarly journals Implementation of High Resolution Whole Genome Array CGH in the Prenatal Clinical Setting: Advantages, Challenges, and Review of the Literature

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Paola Evangelidou ◽  
Angelos Alexandrou ◽  
Maria Moutafi ◽  
Marios Ioannides ◽  
Pavlos Antoniou ◽  
...  
Keyword(s):  
Detection Rate ◽  
Array Cgh ◽  
Chromosomal Abnormalities ◽  
Normal Karyotype ◽  
Comparative Genomic ◽  
Whole Genome ◽  
Review Of The Literature ◽  
Oligonucleotide Arrays ◽  
Ultrasound Findings ◽  
Diagnostic Capacity

Array Comparative Genomic Hybridization analysis is replacing postnatal chromosomal analysis in cases of intellectual disabilities, and it has been postulated that it might also become the first-tier test in prenatal diagnosis. In this study, array CGH was applied in 64 prenatal samples with whole genome oligonucleotide arrays (BlueGnome, Ltd.) on DNA extracted from chorionic villi, amniotic fluid, foetal blood, and skin samples. Results were confirmed with Fluorescence In Situ Hybridization or Real-Time PCR. Fifty-three cases had normal karyotype and abnormal ultrasound findings, and seven samples had balanced rearrangements, five of which also had ultrasound findings. The value of array CGH in the characterization of previously known aberrations in five samples is also presented. Seventeen out of 64 samples carried copy number alterations giving a detection rate of 26.5%. Ten of these represent benign or variables of unknown significance, giving a diagnostic capacity of the method to be 10.9%. If karyotype is performed the additional diagnostic capacity of the method is 5.1% (3/59). This study indicates the ability of array CGH to identify chromosomal abnormalities which cannot be detected during routine prenatal cytogenetic analysis, therefore increasing the overall detection rate. In addition a thorough review of the literature is presented.

scholarly journals A Placental Trisomy 2 Detected by NIPT Evolved in a Fetal Small Supernumerary Marker Chromosome (sSMC).

2020 ◽  
Author(s):  
Justyna Anna Domaradzka ◽  
Marta Deperas ◽  
Ewa Obersztyn ◽  
Anna Kucińska-Chahwan ◽  
Nathalie Brison ◽  
...  
Keyword(s):  
Cell Line ◽  
Chromosomal Abnormalities ◽  
Marker Chromosome ◽  
Prenatal Testing ◽  
Comparative Genomic ◽  
Chromosome 2 ◽  
Non Invasive ◽  
Small Supernumerary Marker Chromosome ◽  
A Cell ◽  
Cytogenetic Analyses

Abstract Background: Non-invasive prenatal testing (NIPT) is known to be more sensitive and more specific for common aneuploidy as well as sex determination at an early pregnancy compared to traditional biochemical and sonographic screening. However, recently the widespread use of the NIPT caused a neglecting of the limitations of this technology. Case presentation: The 38-year-old woman underwent amniocentesis because of a high risk of trisomy 2 revealed by the genome-wide Non-Invasive Prenatal Test (NIPT). The invasive prenatal diagnosis revealed the mosaicism for a small supernumerary marker chromosome sSMC derived from chromosome 2. Interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes revealed three signals of centromere 2 in 30% of the cells. GTG-banded metaphases revealed abnormal karyotype (47,XX,+mar[21]/46,XX[19]) and was confirmed by array comparative genomic hybridization (aCGH). Cytogenetic analyses (FISH, aCGH, karyotype) on fetal skin biopsies were performed and confirmed the genomic gain of the centromeric region of chromosome 2. In the placenta, three cell lines were detected: a normal cell line, a cell line with trisomy 2 and a third one with only the sSMC.Conclusion: Whole-genome Non-Invasive Prenatal Testing allows not only the identification of common fetal trisomies but also diagnosis of rare chromosomal abnormalities. Especially in such cases, it is extremely important to perform not only NIPT verification on a sample of material other than trophoblast, but also to apply appropriate research methods. Such conduct allows detailed analysis of the detected aberration, thus appropriate clinical validity.

scholarly journals A placental trisomy 2 detected by NIPT evolved in a fetal small Supernumerary Marker Chromosome (sSMC)

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Justyna Domaradzka ◽  
Marta Deperas ◽  
Ewa Obersztyn ◽  
Anna Kucińska-Chahwan ◽  
Nathalie Brison ◽  
...  
Keyword(s):  
Cell Line ◽  
Chromosomal Abnormalities ◽  
Marker Chromosome ◽  
Prenatal Testing ◽  
Comparative Genomic ◽  
Chromosome 2 ◽  
Non Invasive ◽  
Small Supernumerary Marker Chromosome ◽  
A Cell ◽  
Cytogenetic Analyses

Abstract Background Non-invasive prenatal testing (NIPT) is a rapidly developing and widely used method in the prenatal screening. Recently, the widespread use of the NIPT caused a neglecting of the limitations of this technology. Case presentation The 38-year-old woman underwent amniocentesis because of a high risk of trisomy 2 revealed by the genome-wide Non-Invasive Prenatal Test (NIPT). The invasive prenatal diagnosis revealed the mosaicism for a small supernumerary marker chromosome sSMC derived from chromosome 2. Interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes revealed three signals of centromere 2 in 30% of the cells. GTG-banded metaphases revealed abnormal karyotype (47,XX,+mar[21]/46,XX[19]) and was confirmed by array comparative genomic hybridization (aCGH). Cytogenetic analyses (FISH, aCGH, karyotype) on fetal skin biopsies were performed and confirmed the genomic gain of the centromeric region of chromosome 2. In the placenta, three cell lines were detected: a normal cell line, a cell line with trisomy 2 and a third one with only the sSMC. Conclusion Whole-genome Non-Invasive Prenatal Testing allows not only the identification of common fetal trisomies but also diagnosis of rare chromosomal abnormalities. Especially in such cases, it is extremely important to perform not only NIPT verification on a sample of material other than trophoblast, but also to apply appropriate research methods. Such conduct allows detailed analysis of the detected aberration, thus appropriate clinical validity.

scholarly journals Early Gastric Cancer: Current Advances of Endoscopic Diagnosis and Treatment

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Linlin Zhu ◽  
Jinyu Qin ◽  
Jin Wang ◽  
Tianjiao Guo ◽  
Zijing Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Gastric Cancer ◽  
Detection Rate ◽  
Diagnostic Yield ◽  
Endoscopic Diagnosis ◽  
Diagnosis And Treatment ◽  
High Detection Rate ◽  
Endoscopic Techniques ◽  
High Detection ◽  
Gastric Cancer Screening

Endoscopy is a major method for early gastric cancer screening because of its high detection rate, but its diagnostic accuracy depends heavily on the availability of endoscopic instruments. Many novel endoscopic techniques have been shown to increase the diagnostic yield of early gastric cancer. With the improved detection rate of EGC, the endoscopic treatment has become widespread due to advances in the instruments available and endoscopist’s experience. The aim of this review is to summarize frequently-used endoscopic diagnosis and treatment in early gastric cancer (EGC).

scholarly journals Security of Things Intrusion Detection System for Smart Healthcare

Electronics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1375
Author(s):  
Celestine Iwendi ◽  
Joseph Henry Anajemba ◽  
Cresantus Biamba ◽  
Desire Ngabo
Keyword(s):  
Genetic Algorithm ◽  
Intrusion Detection ◽  
False Alarm ◽  
False Alarm Rate ◽  
Detection Rate ◽  
Web Security ◽  
Intrusion Detection Systems ◽  
High Detection Rate ◽  
Detection Systems ◽  
Smart Healthcare

Web security plays a very crucial role in the Security of Things (SoT) paradigm for smart healthcare and will continue to be impactful in medical infrastructures in the near future. This paper addressed a key component of security-intrusion detection systems due to the number of web security attacks, which have increased dramatically in recent years in healthcare, as well as the privacy issues. Various intrusion-detection systems have been proposed in different works to detect cyber threats in smart healthcare and to identify network-based attacks and privacy violations. This study was carried out as a result of the limitations of the intrusion detection systems in responding to attacks and challenges and in implementing privacy control and attacks in the smart healthcare industry. The research proposed a machine learning support system that combined a Random Forest (RF) and a genetic algorithm: a feature optimization method that built new intrusion detection systems with a high detection rate and a more accurate false alarm rate. To optimize the functionality of our approach, a weighted genetic algorithm and RF were combined to generate the best subset of functionality that achieved a high detection rate and a low false alarm rate. This study used the NSL-KDD dataset to simultaneously classify RF, Naive Bayes (NB) and logistic regression classifiers for machine learning. The results confirmed the importance of optimizing functionality, which gave better results in terms of the false alarm rate, precision, detection rate, recall and F1 metrics. The combination of our genetic algorithm and RF models achieved a detection rate of 98.81% and a false alarm rate of 0.8%. This research raised awareness of privacy and authentication in the smart healthcare domain, wireless communications and privacy control and developed the necessary intelligent and efficient web system. Furthermore, the proposed algorithm was applied to examine the F1-score and precisionperformance as compared to the NSL-KDD and CSE-CIC-IDS2018 datasets using different scaling factors. The results showed that the proposed GA was greatly optimized, for which the average precision was optimized by 5.65% and the average F1-score by 8.2%.

scholarly journals Performance of Cell-Free DNA Screening for Fetal Common Aneuploidies and Sex Chromosomal Abnormalities: A Prospective Study from a Less Developed Autonomous Region in Mainland China

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 478
Author(s):  
Yunli Lai ◽  
Xiaofan Zhu ◽  
Sheng He ◽  
Zirui Dong ◽  
Yanqing Tang ◽  
...  
Keyword(s):  
Sex Chromosome ◽  
Chromosomal Abnormalities ◽  
False Negative ◽  
Prenatal Testing ◽  
Read Depth ◽  
Trisomy 13 ◽  
Prognostic Information ◽  
Aneuploidy Screening ◽  
Predictive Values ◽  
Risk Result

To evaluate the performance of noninvasive prenatal screening (NIPS) in the detection of common aneuploidies in a population-based study, a total of 86,262 single pregnancies referred for NIPS were prospectively recruited. Among 86,193 pregnancies with reportable results, follow-up was successfully conducted in 1160 fetuses reported with a high-risk result by NIPS and 82,511 cases (95.7%) with a low-risk result. The screen-positive rate (SPR) of common aneuploidies and sex chromosome abnormalities (SCAs) provided by NIPS were 0.7% (586/83,671) and 0.6% (505/83,671), respectively. The positive predictive values (PPVs) for Trisomy 21, Trisomy 18, Trisomy 13 and SCAs were calculated as 89.7%, 84.0%, 52.6% and 38.0%, respectively. In addition, less rare chromosomal abnormalities, including copy number variants (CNVs), were detected, compared with those reported by NIPS with higher read-depth. Among these rare abnormalities, only 23.2% (13/56) were confirmed by prenatal diagnosis. In total, four common trisomy cases were found to be false negative, resulting in a rate of 0.48/10,000 (4/83,671). In summary, this study conducted in an underdeveloped region with limited support for the new technology development and lack of cost-effective prenatal testing demonstrates the importance of implementing routine aneuploidy screening in the public sector for providing early detection and precise prognostic information.

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