Confined placental mosaicism of double trisomies 9 and 21: discrepancy between non-invasive prenatal testing, chorionic villus sampling and postnatal confirmation

<p>Prenatal screening for chromosomal abnormalities has two components i.e. prenatal screening (maternal serum screening and cell-free fetal DNA screening) and prenatal diagnosis (chorionic villus sampling, amniocentesis, and cordocentesis). Prenatal testing in the past decade is evolving towards non-invasive methods to determine the chromosome abnormality disorders in the fetus without incurring the risk of miscarriage. Conventional tools for prenatal screening included maternal age, maternal serum markers, ultrasound marker (nuchal thickness), and their combinations. With the increased risk of screening test patients were offered diagnostic tests (chorionic villus sampling, amniocentesis, and cordocentesis). After the availability of noninvasive prenatal tests for commercial use in 2011, a great marketing drive is there to establish it as a master tool for prenatal testing. However various society guidelines i.e. ACOG, RCOG, and ISUOG have clearly stated that cell-free fetal DNA based noninvasive prenatal tests is a screening test, not a diagnostic test. In the succeeding paragraph, we will review current trends in the field of cell-free fetal DNA noninvasive prenatal tests and the relevance of invasive testing in the context of noninvasive prenatal tests. Noninvasive prenatal tests does not entirely replace invasive prenatal testing procedures. Positive noninvasive prenatal tests findings must be confirmed by diagnostic tests based on an invasive sample source, mainly chorionic villus sampling or amniocentesis due to false positive and false negative reports of cell-free fetal DNA based tests. Continuing research and development efforts are focused on overriding noninvasive prenatal tests limitations. Recent studies show that procedure-associated risks in the case of prenatal invasive testing are very low as compared to previous studies. Prenatal invasive testing will remain as the backbone of prenatal diagnostic testing until the limitation of noninvasive prenatal tests is overcome.</p>

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Noninvasive Prenatal Testing as Compared to Chorionic Villus Sampling Is More Sensitive for the Detection of Confined Placental Mosaicism Involving the Cytotrophoblast

Obstetrical & Gynecological Survey ◽

10.1097/01.ogx.0000733524.21362.2c ◽

2021 ◽

Vol 76 (2) ◽

pp. 81-83

Author(s):

Diane Van Opstal ◽

Geerke M. Eggenhuizen ◽

Marieke Joosten ◽

Karin Diderich ◽

Lutgarde Govaerts ◽

...

Keyword(s):

Chorionic Villus ◽

Prenatal Testing ◽

Chorionic Villus Sampling ◽

Noninvasive Prenatal Testing ◽

Placental Mosaicism

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Cell free DNA: revolution in molecular diagnostics – the journey so far

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2019-0012 ◽

2020 ◽

Vol 41 (1) ◽

Cited By ~ 1

Author(s):

Kajal Nandi ◽

Rashmi Verma ◽

Rajni Dawar ◽

Binita Goswami

Keyword(s):

Chorionic Villus ◽

Prenatal Testing ◽

Blood Stream ◽

The Body ◽

Chorionic Villus Sampling ◽

Cell Free Dna ◽

Genetic Profiling ◽

Non Invasive ◽

Free Dna

AbstractCell free DNA (cf-DNA) refers to all non -ncapsulated DNA present in the blood stream which may originate from apoptotic cells as a part of the physiological cell turnover, or from cancer cells or fetal cells. Recent studies have highlighted the utility of cfDNA analysis for genetic profiling of cancer, non-invasive prenatal testing besides many other clinical applications. In our review we discuss the sources of cfDNA in the body, the techniques most commonly being used for its isolation and analysis, the applications of cfDNA testing and the associated pros-cons. We conclude that for prenatal testing, cfDNA analysis provides an effective, non-invasive and safer alternative to traditional amniocentesis and chorionic villus sampling tests. Also, in cancer patients, cfDNA analysis is useful for genetic profiling and follow-up during treatment. However, standardization of methods of isolation and analysis has become crucial for the success of widespread use of cfDNA analysis.

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Discordant structural chromosomal aberrations in chorionic villi and amniotic fluid leading to a formation of an isochromosome 21: a case report

Molecular Cytogenetics ◽

10.1186/s13039-021-00549-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Eini Westenius ◽

Maria Pettersson ◽

Erik Björck

Keyword(s):

Amniotic Fluid ◽

Chromosomal Aberrations ◽

Trisomy 21 ◽

Chorionic Villus ◽

Prenatal Testing ◽

Chorionic Villus Sampling ◽

Chorionic Villi ◽

Non Invasive ◽

Increased Risk ◽

A Cell

Abstract Background Fetoplacental discrepancies occur in approximately 1–2% of analyzed prenatal cases. They are typically due to confined placental mosaicism, where an aberration is observed in the placental cells but not found in the fetal cells. Confined placental mosaicism usually involves aneuploidies and more sparsely structural chromosomal aberrations. To the best of our knowledge, this is the first reported case of a discrepancy in the analyses of chorionic villus sampling and amniocentesis involving two different structural chromosomal aberrations of chromosome 21. Case presentation We report a 33-year-old woman who was referred for a non-invasive prenatal testing due to an increased risk of trisomy 21 gleaned from a combined ultrasound and blood test. The non-invasive prenatal testing showed an increased risk of trisomy 21 with a normalized coverage signal that did not match the fetal cell-free DNA fraction. Rapid aneuploidy detection performed on uncultured chorionic villi indicated mosaicism for trisomy 21. The follow-up analyses revealed discordant chromosomal aberrations: 46,XY,der(21)t(10;21)(p11.21;q10) in the analysis of the chorionic villus sampling and 46,XY, + 21,der(21;21)(q10;q10) in the analysis of the amniocentesis. Thus, the analyses indicated mosaicism for a cell line containing trisomy 21 and a cell line containing a partially duplicated short arm of chromosome 10 in the chorionic villi and complete trisomy 21 resulting from an isochromosome 21 in the amniotic fluid. The analyses of the lymphocytes and the fibroblasts of the woman were normal. Conclusions We propose a multiple-step mechanism as a possible theoretical explanation for the formation of these discordant structural chromosomal aberrations in the chorionic villi and amniotic fluid. With this case report, we want to highlight the importance of understanding the possible underlying embryological mechanisms when interpreting results from different prenatal analyses.

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Risk of fetal mosaicism when placental mosaicism is diagnosed by chorionic villus sampling

American Journal of Obstetrics and Gynecology ◽

10.1016/s0002-9378(96)70312-5 ◽

1996 ◽

Vol 174 (3) ◽

pp. 850-855 ◽

Cited By ~ 50

Author(s):

Owen P. Phillips ◽

Avirachan T. Tharapel ◽

Jody L. Lerner ◽

Vicki M. Park ◽

Stephen S. Wachtel ◽

...

Keyword(s):

Chorionic Villus ◽

Chorionic Villus Sampling ◽

Placental Mosaicism

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Non Invasive Prenatal Diagnosis of Aneuploidy: Next Generation Sequencing or Fetal DNA Enrichment?

Balkan Journal of Medical Genetics ◽

10.2478/v10034-012-0013-z ◽

2012 ◽

Vol 15 (Supplement) ◽

pp. 17-26 ◽

Cited By ~ 3

Author(s):

Neil D. Avent ◽

A Webb ◽

TE Madgett ◽

T Miran ◽

K Sillence ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Detection Rate ◽

Improve Patient Safety ◽

Chorionic Villus ◽

Diagnostic Procedures ◽

Chorionic Villus Sampling ◽

Group Status ◽

Non Invasive ◽

Fetal Dna ◽

Cell Free Fetal Dna

ABSTRACT Current invasive procedures [amniocentesis and chorionic villus sampling (CVS)] pose a risk to mother and fetus and such diagnostic procedures are available only to high risk pregnancies limiting aneuploidy detection rate. This review seeks to highlight the necessity of investing in non invasive prenatal diagnosis (NIPD) and how NIPD would improve patient safety and detection rate as well as allowing detection earlier in pregnancy. Non invasive prenatal diagnosis can take either a proteomics approach or nucleic acid-based approach; this review focuses on the latter. Since the discovery of cell free fetal DNA (cffDNA) and fetal RNA in maternal plasma, procedures have been developed for detection for monogenic traits and for some have become well established (e.g., RHD blood group status). However, NIPD of aneuploidies remains technically challenging. This review examines currently published literature evaluating techniques and approaches that have been suggested and developed for aneuploidy detection, highlighting their advantages and limitations and areas for further research.

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Invasive Prenatal Diagnosis

10.2310/obg.19130 ◽

2020 ◽

Author(s):

Kimberly Zayhowski

Keyword(s):

Genetic Counseling ◽

Prenatal Diagnosis ◽

Genetic Testing ◽

Prenatal Care ◽

Chorionic Villus ◽

Prenatal Testing ◽

Chorionic Villus Sampling ◽

Genetic Tests ◽

Genetic Technologies ◽

Invasive Techniques

Despite recent advances in genetic technologies that are making invasive prenatal diagnosis less common, amniocentesis and chorionic villus sampling (CVS) remain an integral part of prenatal care. A multitude of tests, including a variety of genetic tests, can be performed using samples collected from either procedure. Although invasive testing has limitations, many genetic conditions can only be diagnosed through invasive techniques during pregnancy. Invasive testing continues to assist patients and providers in making informed decisions regarding the care of pregnancies. This review details amniocentesis and chorionic villus sampling with a focus on genetic testing, describing why the tests are performed, the way in which they are performed, and the associated limitations and complications of the procedures. This review 5 figures, 3 tables, and 26 references. Keywords: prenatal diagnosis, amniocentesis, chorionic villus sampling, genetic testing, genetic counseling, invasive prenatal testing, pregnancy, aneuploidy

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Uptake of Noninvasive Prenatal Testing in Chinese Women following Positive Down Syndrome Screening

Fetal Diagnosis and Therapy ◽

10.1159/000365811 ◽

2014 ◽

Vol 37 (2) ◽

pp. 141-147 ◽

Cited By ~ 7

Author(s):

C.F. Poon ◽

W.C. Tse ◽

K.O. Kou ◽

K.Y. Leung

Keyword(s):

Down Syndrome ◽

Chinese Women ◽

Multivariable Analysis ◽

Chorionic Villus ◽

Prenatal Testing ◽

First Trimester ◽

Screening Methods ◽

Chorionic Villus Sampling ◽

Noninvasive Prenatal Testing ◽

Down Syndrome Screening

Objectives: To investigate how the introduction of noninvasive prenatal testing (NIPT) influenced women's testing choices following a positive Down syndrome screening. Methods: A retrospective study was conducted to compare differences in the uptake rates of invasive prenatal diagnosis (IPD) or no testing in one public hospital 1 year before (pre-NIPT) and 1 and 2 years after the introduction of NIPT in private in August 2011 using descriptive analysis and a χ2 test. Conventional screening was funded publicly, but NIPT was not. Multivariable binary logistic regression was used to determine factors affecting choices. Results: In pre-NIPT and in years 1 and 2 after the introduction of NIPT, 306, 362 and 401 women who screened positive were seen, respectively. In year 1 and year 2, 12.6 and 26.7% of them underwent NIPT while IPD was decreased by 16.3 and 25.6%, respectively (p < 0.001). Both chorionic villus sampling and amniocentesis decreased in year 1, but only the former in year 2. However, the rate of declining further testing was similar before and after NIPT (p = 0.213). In multivariable analysis, first trimester screening, nulliparity and working women were significant predictors of accepting NIPT, while only nulliparity was a predictor of declining IPD (OR = 0.61). Conclusions: Introduction of NIPT resulted in a significant decrease in IPD for 2 consecutive years.

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