scholarly journals Prenatal maternal plasma DNA screening for cystic fibrosis: A computer modelling study of screening performance

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1896
Author(s):  
Robert W. Old ◽  
Jonathan P. Bestwick ◽  
Nicholas J. Wald
Keyword(s):  
Cystic Fibrosis ◽  
Detection Rate ◽  
Computer Modelling ◽  
False Positive Rate ◽  
Chorionic Villus ◽  
Maternal Plasma ◽  
Carrier Testing ◽  
Chorionic Villus Sampling ◽  
Carrier Status ◽  
Dna Fragments

Background: Prenatal cystic fibrosis (CF) screening is currently based on determining the carrier status of both parents. We propose a new method based only on the analysis of DNA in maternal plasma. Methods: The method relies on the quantitative amplification of the CF gene to determine the percentage of DNA fragments in maternal plasma at targeted CF mutation sites that carry a CF mutation. Computer modelling was carried out to estimate the distributions of these percentages in pregnancies with and without a fetus affected with CF. This was done according to the number of DNA fragments counted and fetal fraction, using the 23 CF mutations recommended by the American College of Medical Genetics for parental carrier testing. Results: The estimated detection rate (sensitivity) is 70% (100% of those detected using the 23 mutations), the false-positive rate 0.002%, and the odds of being affected given a positive screening result 14:1, compared with 70%, 0.12%, and 1:3, respectively, with current prenatal screening based on parental carrier testing. Conclusions: Compared with current screening practice based on parental carrier testing, the proposed method would substantially reduce the number of invasive diagnostic procedures (amniocentesis or chorionic villus sampling) without reducing the CF detection rate. The expected advantages of the proposed method justify carrying out the necessary test development for use in a clinical validation study.

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

2012 ◽  
Vol 15 (Supplement) ◽  
pp. 17-26 ◽  
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.

scholarly journals Whole-genome fetal and maternal DNA methylation analysis using MeDIP-NGS for the identification of differentially methylated regions

2016 ◽  
Vol 98 ◽  
Author(s):  
ANNA KERAVNOU ◽  
MARIOS IOANNIDES ◽  
KYRIAKOS TSANGARAS ◽  
CHARALAMBOS LOIZIDES ◽  
MICHAEL D. HADJIDANIEL ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Chorionic Villus ◽  
Maternal Blood ◽  
Maternal Plasma ◽  
Chorionic Villus Sampling ◽  
Whole Genome ◽  
Differentially Methylated Regions ◽  
Epigenetic Marker ◽  
Novel Approach ◽  
Targeted Enrichment

SummaryDNA methylation is an epigenetic marker that has been shown to vary significantly across different tissues. Taking advantage of the methylation differences between placenta-derived cell-free DNA and maternal blood, several groups employed different approaches for the discovery of fetal-specific biomarkers. The aim of this study was to analyse whole-genome fetal and maternal methylomes in order to identify and confirm the presence of differentially methylated regions (DMRs). We have initially utilized methylated DNA immunoprecipitation (MeDIP) and next-generation sequencing (NGS) to identify genome-wide DMRs between chorionic villus sampling (CVS) and female non-pregnant plasma (PL) and peripheral blood (WBF) samples. Next, using specific criteria, 331 fetal-specific DMRs were selected and confirmed in eight CVS, eight WBF and eight PL samples by combining MeDIP and in-solution targeted enrichment followed by NGS. Results showed higher enrichment in CVS samples as compared to both WBF and PL samples, confirming the distinct methylation levels between fetal and maternal DNA for the selected DMRs. We have successfully implemented a novel approach for the discovery and confirmation of a significant number of fetal-specific DMRs by combining for the first time MeDIP and in-solution targeted enrichment followed by NGS. The implementation of this double-enrichment approach is highly efficient and enables the detailed analysis of multiple DMRs by targeted NGS. Also, this is, to our knowledge, the first reported application of MeDIP on plasma samples, which leverages the implementation of our enrichment methodology in the detection of fetal abnormalities in maternal plasma.

Selective Abortion: A New Moral Order? Consensus and Debate in the Medical Community

1995 ◽  
Vol 25 (1) ◽  
pp. 65-84 ◽  
Author(s):  
Louise Bouchard ◽  
Marc Renaud ◽  
Odile Kremp ◽  
Louis Dallaire
Keyword(s):  
Cystic Fibrosis ◽  
Trisomy 21 ◽  
Chorionic Villus ◽  
Medical Community ◽  
Moral Order ◽  
Chorionic Villus Sampling ◽  
Fetal Anomalies ◽  
Huntington's Chorea ◽  
Selective Abortion ◽  
French Speaking

The authors discuss the results of a survey of the attitudes of Canadian and French (Picardie, Nord-Pas de Calais) physicians toward selective abortion of fetal anomalies detected by ultrasound, amniocentesis, or chorionic villus sampling. The study documents the threshold of acceptability of abortion of fetuses with selected anomalies, as well as the physicians' own perceptions of their role in the decision to abort. While there was no consensus among all Canadian physicians regarding the acceptability of abortion, more than 55 percent from France and Quebec would accept selective abortion of a fetus affected with trisomy 21, Duchenne muscular dystrophy, cystic fibrosis, Huntington's chorea, or spina bifida. In the province of Quebec, Anglophone physicians showed a greater acceptance of abortion than did their French-speaking colleagues. In reference to the physician's role in the decision to abort, French physicians are more directive than North American physicians. Cultural predispositions may explain these differences in attitudes.

FETAL NUCLEIC ACIDS IN MATERNAL PLASMA

2006 ◽  
Vol 17 (2) ◽  
pp. 125-137
Author(s):  
TRACY YH LEE ◽  
YM DENNIS LO
Keyword(s):  
Prenatal Diagnosis ◽  
Pregnant Women ◽  
Chorionic Villus ◽  
Fetal Loss ◽  
Maternal Plasma ◽  
Chorionic Villus Sampling ◽  
Invasive Procedures ◽  
Noninvasive Prenatal Diagnosis ◽  
The World ◽  
Definitive Methods

Prenatal diagnosis is now an established part of modern obstetrical practice around the world. While the current definitive methods for prenatal diagnosis rely mainly on invasive procedures such as chorionic villus sampling and amniocentesis, such procedures carry a low but definite risk of fetal loss. As a consequence of the procedure-associated risk of miscarriage, prenatal diagnosis is currently limited to pregnant women with an increased likelihood of bearing an abnormal fetus. To extend the application of prenatal diagnosis to all pregnant women, it has been a long-sought goal of researchers worldwide to introduce safer methods for prenatal diagnosis, towards noninvasive prenatal diagnosis.

Cascade Testing for the Identification of Carriers of Cystic Fibrosis

1994 ◽  
Vol 1 (3) ◽  
pp. 159-164 ◽  
Author(s):  
Susan Holloway ◽  
David J H Brock
Keyword(s):  
Cystic Fibrosis ◽  
General Population ◽  
Positive Result ◽  
Detection Rate ◽  
Reproductive Age ◽  
Carrier Status ◽  
Cascade Testing ◽  
The Family

It has been suggested that cascade testing, in which relatives of a person affected with cystic fibrosis (CF) are tested for carrier status, is preferable to screening individuals in the general population. This idea was examined by calculating the number of relatives requiring testing, assuming that it is necessary to identify all those of reproductive age no more distantly related to the proband than second cousins. Two hypothetical programmes were used, in each of which only blood relatives of an affected proband were tested and subsequent analysis applied to relatives of those with a positive result. If started in the grandparental generation, cascade testing of about 28 relatives for each proband would detect 86.4% of carriers in the family. If only carried out for the parental generation and their descendants, testing of about 35 relatives for each proband would detect 92.1% of carriers in the family. If cascade testing were restricted to the second cousin level, however, these programmes would only detect between 8 and 24% of all carrier couples. This contrasts with the 50% detection rate that has already been demonstrated for antenatal CF screening.

scholarly journals Non invasive prenatal diagnosis of ?- Thalassemia, A narrative review study

2017 ◽  
Vol 16 (2) ◽  
pp. 196-202 ◽  
Author(s):  
Mandana Zafari ◽  
Mehrnoush Kowsaryan ◽  
Pooria Gill ◽  
Ali Banihashemi
Keyword(s):  
Prenatal Diagnosis ◽  
Medical Science ◽  
Chorionic Villus ◽  
Maternal Plasma ◽  
Paternal Allele ◽  
Chorionic Villus Sampling ◽  
Non Invasive ◽  
Invasive Method ◽  
Review Study ◽  
Chromosomal Aneuploidies

?- Thalassemia is major monogenic disorder. A practical way to prevention of Thalassemia is identification of carries couples; genetic counseling and offer prenatal diagnose services for both carrier couples. Routine prenatal diagnose are chorionic villus sampling and amniocentesis, but both of them are invasive method and they can be ended to bleeding and pregnancy loss. Recently non invasive prenatal diagnosis has been done by researchers for early detection of pre-eclampsia, chromosomal aneuploidies, RhD-genotyping. Regarding non invasive prenatal diagnosis of ?- Thalassemia, detection of paternally inherited mutation in maternal plasma is possible. If the fetus inherited normal paternal allele the performance of invasive method it is not necessary, so this method can be eliminate 50% performance of routine prenatal diagnosis.Bangladesh Journal of Medical Science Vol.16(2) 2017 p.196-202

scholarly journals Ultrasound-Guided Invasive Procedures in Genetic Prenatal Diagnostics

2011 ◽  
Vol 5 (2) ◽  
pp. 137-139
Author(s):  
Miroslaw Wielgos ◽  
Piotr Wegrzyn
Keyword(s):  
High Risk ◽  
False Positive Rate ◽  
Chorionic Villus ◽  
High Risk Group ◽  
Screening Methods ◽  
Chorionic Villus Sampling ◽  
Invasive Procedures ◽  
Fetal Blood Sampling ◽  
Wide Range ◽  
Positive Rate

ABSTRACT There is a wide range of noninvasive screening methods that aim to identify the subgroup of fetuses that are in a high risk of chromosomal defects. Invasive procedures should be offered to women in the high-risk group identified with the highest possible detection rate and the lowest false-positive rate. The method of choice at 11 + 0 - 13 + 6 weeks is chorionic villus sampling. An early amniocentesis is much more dangerous and should be abandoned. CVS should be performed not earlier than at 11 + 0 weeks of pregnancy. Amniocentesis should be performed no earlier that at 15 + 0 weeks. Earlier procedure is associated with significantly higher rate of talipes equinovarius, amniotic fluid leakage and miscarriage. The umbilical cord insertion is a preferable site for fetal blood sampling. Care must be taken to distinguish between the vein and the artery, and the vein must be sampled, not the artery. The operator's experience is very important issue. It has been postulated that to achieve a reasonable experience one should perform a minimum of 100 chorionic villus samplings, and a reasonable number of invasive procedures should be performed yearly.

Sign in / Sign up

Export Citation Format

Share Document