scholarly journals Screening for Fetal Aneuploidy and Sex Chromosomal Anomalies in a Pregnant Woman With Mosaicism for Turner Syndrome—Applications and Advantages of Cell-Based NIPT

2021 ◽  
Vol 12 ◽  
Author(s):  
Line Dahl Jeppesen ◽  
Lotte Hatt ◽  
Ripudaman Singh ◽  
Palle Schelde ◽  
Lotte Andreasen ◽  
...  
Keyword(s):  
Pregnant Woman ◽  
Turner Syndrome ◽  
First Trimester ◽  
Maternal Blood ◽  
Chromosomal Microarray ◽  
Chromosomal Anomalies ◽  
Str Analysis ◽  
High Background ◽  
Fetal Cells ◽  
Fetal Fraction

Background: Cell-free NIPT and cell-based NIPT are risk-free testing options using maternal blood samples to screen for fetal aneuploidies, but the methods differ. For cell-free NIPT, the fetal fraction of cell-free DNA in plasma is analyzed with a high background of maternal DNA. In contrast, for cell-based NIPT, a limited number of the rare, intact fetal cells are isolated for the genetic analysis. This case demonstrates the differences regarding testing for fetal sex-chromosomes anomalies (SCAs) between these two tests.Materials and Methods: A pregnant woman with mosaicism for Turner syndrome opted for NIPT in first trimester. For the cell-free NIPT analysis, DNA extraction, genome-wide massive parallel sequencing, and data analysis were carried out as described by the kit manufacturer (Illumina©, San Diego, CA, USA). For cell-based NIPT, the first sample gave no result, but the woman consented to repeat cell-based NIPT. After whole genome amplification and STR analysis, fetal DNA from three individual fetal cells was subjected to chromosomal microarray (aCGH, Agilent oligoarray, 180 kb).Results: Fetal fraction was 7%, and cell-free NIPT showed 2 copies of chromosomes 13, 18, and 21 and a decreased proportion of chromosome X, suggestive of fetal Turner syndrome. In contrast, the cell-based NIPT result showed no aneuploidy and two X-chromosomes in the fetus.Conclusion: cell-based NIPT may provide a non-invasive testing option to screen for SCAs in women with mosaicism for monosomy-X in blood, where cell-free NIPT cannot discriminate whether the X-loss is maternal or fetal.

scholarly journals First-trimester Screening: An Overview

2005 ◽  
Vol 53 (3) ◽  
pp. 281-283 ◽  
Author(s):  
Bernd Eiben ◽  
Ralf Glaubitz
Keyword(s):  
Prenatal Screening ◽  
Heart Defects ◽  
Protein A ◽  
Nasal Bone ◽  
First Trimester ◽  
Nuchal Translucency ◽  
Maternal Blood ◽  
Chromosomal Anomalies ◽  
Detection Rates ◽  
Trimester Screening

An improvement in prenatal screening for chromosomal defects has been achieved by combining sonography and biochemical markers. Analyzing markers taken from maternal blood such as pregnancy-associated plasma protein A and free β-human chorionic gonadotropin in combination with the ultrasound marker nuchal translucency provides detection rates of 90% for the most important chromosomal anomalies. In addition, nuchal translucency is a marker for severe heart defects. This report discusses the potential of new markers such as the nasal bone.

scholarly journals Report of a pregnant woman with mosaic Turner syndrome

2021 ◽  
pp. 46-48
Author(s):  
Yunus Emre TOPDAĞI
Keyword(s):  
Pregnant Woman ◽  
High Risk ◽  
Turner Syndrome ◽  
First Trimester ◽  
Cardiovascular Complications ◽  
Incidence Rates ◽  
Spontaneous Pregnancy ◽  
High Incidence ◽  
History Of

Spontaneous pregnancy in women with Turner syndrome is rare (5%) and relative- ly high risk. A number of methods to preserve fertility in such women have been discussed. Careful follow-up is required during these pregnancies due to the high incidence rates of neonatal, obstetric, maternal, and cardiovascular complications. A 39-year-old multigravid woman (G5, P3, A2) with mosaic Turner syndrome with a history of three spontaneous pregnancies and two miscarriages was evaluated at our clinic. The analysis showed mos 45,X [9]/46,XX [38] mosaic Turner syndrome. Her first and fourth pregnancies resulted in miscarriages during the first trimester. Here, we discuss a pregnant woman with mosaic Turner syndrome with unaffected fertility but with a history of spontaneous pregnancies/miscarriages, with reference to the current literature.

First trimester prenatal diagnosis of trisomy 21 in fetal cells from maternal blood

The Lancet ◽  
1992 ◽  
Vol 340 (8826) ◽  
pp. 1033 ◽  
Author(s):  
Sherman Elias ◽  
James Price ◽  
Michael Dockter ◽  
Stephen Wachtel ◽  
Avirachan Tharapel ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Trisomy 21 ◽  
First Trimester ◽  
Maternal Blood ◽  
Fetal Cells

scholarly journals Cell-Free DNA in the Investigation of Miscarriage

2020 ◽  
Vol 9 (11) ◽  
pp. 3428
Author(s):  
Emily Colley ◽  
Adam J. Devall ◽  
Helen Williams ◽  
Susan Hamilton ◽  
Paul Smith ◽  
...  
Keyword(s):  
Chromosomal Abnormalities ◽  
First Trimester ◽  
Maternal Blood ◽  
Tissue Cell ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna ◽  
Genome Wide ◽  
Prenatal Test ◽  
Fetal Fraction

Approximately one in four pregnancies result in pregnancy loss, and ~50% of these miscarriages are caused by chromosomal abnormalities. Genetic investigations are recommended after three consecutive miscarriages on products of conception (POC) tissue. Cell-free DNA (cfDNA) has been utilised for prenatal screening, but very little work has been carried out in nonviable pregnancies. We investigated the use of cfDNA from maternal blood to identify chromosomal abnormalities in miscarriage. One hundred and two blood samples from women experiencing a first trimester miscarriage were collected and stored. The mean gestational age was 7.1 weeks (range: 5–11 weeks). In this research, samples without a genetic test result from POC were not analysed. CfDNA was extracted and analysed using a modified commercial genome-wide non-invasive prenatal test. No results were provided to the patient. In 57 samples, cytogenetic results from POC analysis were available. Chromosomal abnormalities were identified in 47% (27/57) of POC analyses, and cfDNA analysis correctly identified 59% (16/27) of these. In total, 75% (43/57) of results were correctly identified. The average cfDNA fetal fraction was 6% (2–19%). In conclusion, cfDNA can be used to detect chromosomal abnormalities in miscarriages where the ‘fetal fraction’ is high enough; however, more studies are required to identify variables that can affect the overall results.

scholarly journals Evaluation of a Microhaplotype-Based Noninvasive Prenatal Test in Twin Gestations: Determination of Paternity, Zygosity, and Fetal Fraction

Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 26
Author(s):  
Zhaochen Bai ◽  
Hu Zhao ◽  
Shaobin Lin ◽  
Linhuan Huang ◽  
Zhiming He ◽  
...  
Keyword(s):  
Prenatal Testing ◽  
Maternal Plasma ◽  
Clinical Settings ◽  
Str Analysis ◽  
Forensic Research ◽  
Combined Use ◽  
Prenatal Test ◽  
Mz Twins ◽  
Twin Pregnancies ◽  
Fetal Fraction

As a novel type of genetic marker, the microhaplotype has shown promising potential in forensic research. In the present study, we analyzed maternal plasma cell-free DNA (cfDNA) samples from twin pregnancies to validate microhaplotype-based noninvasive prenatal testing (NIPT) for paternity, zygosity, and fetal fraction (FF). Paternity was determined with the combined use of the relMix package, zygosity was evaluated by examining the presence of informative loci with two fetal genome complements, and FF was assessed through fetal allele ratios. Paternity was determined in 19 twin cases, among which 13 cases were considered dizygotic (DZ) twins based on the presence of 3~10 informative loci and the remaining 6 cases were considered monozygotic (MZ) twins because no informative locus was observed. With the fetal genomic genotypes as a reference, the accuracy of paternity and zygosity determination were confirmed by standard short tandem repeat (STR) analysis. Moreover, the lower FF, higher FF, and combined FF in each DZ plasma sample were closely related to the estimated value. This present preliminary study proposes that microhaplotype-based NIPT is applicable for paternity, zygosity, and FF determination in twin pregnancies, which are expected to be advantageous for both forensic and clinical settings.

scholarly journals A prenatal diagnosis case of partial duplication 21q21.1-q21.2 with normal phenotype maternally inherited

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Chunyan Jin ◽  
Zhiping Gu ◽  
Xiaohan Jiang ◽  
Pei Yu ◽  
Tianhui Xu
Keyword(s):  
Down Syndrome ◽  
Pregnant Woman ◽  
Prenatal Testing ◽  
Chromosome 21 ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Serological Screening ◽  
Partial Duplication ◽  
Her Family ◽  
Clinical Consequences

Abstract Background Down syndrome is characterized by trisomy 21 or partial duplication of chromosome 21. Extensive studies have focused on the identification of the Down Syndrome Critical Region (DSCR). We aim to provide evidence that duplication of 21q21.1-q21.2 should not be included in the DSCR and it has no clinical consequences on the phenotype. Case presentation Because serological screening was not performed at the appropriate gestational age, noninvasive prenatal testing (NIPT) analysis was performed for a pregnant woman with normal prenatal examinations at 22 weeks of gestation. The NIPT results revealed a 5.8 Mb maternally inherited duplication of 21q21.1-q21.2. To assess whether the fetus also carried this duplication, ultrasound-guided amniocentesis was conducted, and the result of chromosomal microarray analysis (CMA) with amniotic fluid showed a 6.7 Mb duplication of 21q21.1-q21.2 (ranging from position 18,981,715 to 25,707,009). This partial duplication of 21q21.1-q21.2 in the fetus was maternally inherited. After genetic counseling, the pregnant woman and her family decided to continue the pregnancy. Conclusion Our case clearly indicates that 21q21.1-q21.2 duplication is not included in the DSCR and most likely has no clinical consequences on phenotype.

scholarly journals Development of a Specific Monoclonal Antibody to Detect Male Cells Expressing the RPS4Y1 Protein

2021 ◽  
Vol 22 (4) ◽  
pp. 2001
Author(s):  
Silvia Spena ◽  
Chiara Cordiglieri ◽  
Isabella Garagiola ◽  
Flora Peyvandi
Keyword(s):  
Monoclonal Antibody ◽  
Prenatal Diagnosis ◽  
Maternal Blood ◽  
Limiting Factors ◽  
Inherited Disease ◽  
Specific Monoclonal Antibody ◽  
Native Form ◽  
Fetal Cells ◽  
Non Invasive ◽  
Reliable Isolation

Hemophilia is an X-linked recessive bleeding disorder. In pregnant women carrier of hemophilia, the fetal sex can be determined by non-invasive analysis of fetal DNA circulating in the maternal blood. However, in case of a male fetus, conventional invasive procedures are required for the diagnosis of hemophilia. Fetal cells, circulating in the maternal bloodstream, are an ideal target for a safe non-invasive prenatal diagnosis. Nevertheless, the small number of cells and the lack of specific fetal markers have been the most limiting factors for their isolation. We aimed to develop monoclonal antibodies (mAbs) against the ribosomal protein RPS4Y1 expressed in male cells. By Western blotting, immunoprecipitation and immunofluorescence analyses performed on cell lysates from male human hepatoma (HepG2) and female human embryonic kidney (HEK293) we developed and characterized a specific monoclonal antibody against the native form of the male RPS4Y1 protein that can distinguish male from female cells. The availability of the RPS4Y1-targeting monoclonal antibody should facilitate the development of novel methods for the reliable isolation of male fetal cells from the maternal blood and their future use for non-invasive prenatal diagnosis of X-linked inherited disease such as hemophilia.

scholarly journals Comparison of Different Blood Collection, Sample Matrix, and Immunoassay Methods in a Prenatal Screening Setting

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Jeroen L. A. Pennings ◽  
Jacqueline E. Siljee ◽  
Sandra Imholz ◽  
Sylwia Kuc ◽  
Annemieke de Vries ◽  
...  
Keyword(s):  
Prenatal Screening ◽  
Protein A ◽  
Correlation Coefficients ◽  
First Trimester ◽  
Dried Blood Spots ◽  
Maternal Blood ◽  
Blood Collection ◽  
Antibody Microarray ◽  
Sample Matrix ◽  
Finger Prick

We compared how measurements of pregnancy-associated plasma protein A (PAPP-A) and the free beta subunit of human chorionic gonadotropin (fβ-hCG) in maternal blood are influenced by different methods for blood collection, sample matrix, and immunoassay platform. Serum and dried blood spots (DBS) were obtained by venipuncture and by finger prick of 19 pregnant women. PAPP-A and fβ-hCG from serum and from DBS were measured by conventional indirect immunoassay on an AutoDELFIA platform and by antibody microarray. We compared methods based on the recoveries for both markers as well as marker levels correlations across samples. All method comparisons showed high correlations for both marker concentrations. Recovery levels of PAPP-A from DBS were 30% lower, while those of fβ-hCG from DBS were 50% higher compared to conventional venipuncture serum. The recoveries were not affected by blood collection or immunoassay method. The high correlation coefficients for both markers indicate that DBS from finger prick can be used reliably in a prenatal screening setting, as a less costly and minimally invasive alternative for venipuncture serum, with great logistical advantages. Additionally, the use of antibody arrays will allow for extending the number of first trimester screening markers on maternal and fetal health.

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