Track topics on Twitter Track topics that are important to you
The objective of this project is to develop a non-invasive prenatal diagnostic test for trisomy 21 which is reliable, sensitive and cost-effective, and thus, offers an alternative to the currently employed invasive diagnostic tests amniocentesis and chorionic villus sampling.
Current prenatal screening methods (blood markers and ultrasound) for trisomy 21 (Down syndrome) detect about 90 % of cases and have a false positive rate of > 90 %. The results of these tests are expressed in risks for trisomy 21, the threshold being in France at 1/250. Women exhibiting a higher risk are offered to undergo invasive diagnostic testing, either by amniocentesis or chorionic villus sampling. However, these invasive diagnostic methods are associated with a considerable risk of miscarriage (1-3 %), and thus underline the importance to develop a safe and non-invasive prenatal diagnostic test for trisomy 21. The investigators have planned to assess the clinical impact of a non-invasive prenatal method to detect Trisomy 21 through genetic analysis of circulating trophoblastic cells.
The investigators have planned and developed the following approach: fetal cells are first enriched from blood of pregnant women, between 7 and 12 weeks gestation, employing the ISET (isolation by size of epithelial tumor cells) technique. Cells presumed to be of fetal origin are microdissected and subsequently genetically analyzed, using STR markers, to verify their fetal nature. The investigators then plan to test two strategies in order to assess the number of copies of chromosome 21. The first one involves the DNA of a single fetal cell to be analyzed with CGH (comparative genomic hybridization) array. In fact, our team has already developed an application of the metaphase CGH method to single cells isolated by ISET in which we were able to demonstrate the gain of chromosome 21 DNA in single fetal cells isolated from cord blood of a fetus with Down syndrome. The second strategy will be accomplished with the use of quantitative fluorescent PCR analysis of short tandem repeats (STRs), applied to single cells. At least 5-8 highly polymorphic STR markers specific for chromosome 21 will be tested to minimize the effects of a phenomenon called allele drop out, in which one allele fails to amplify, and to maximize the number of triallelic signals for an accurate diagnosis of disomy or trisomy 21.
This survey is performed in collaboration with the Department of Gynaecology-Obstetrics - Reproductive Medicine of Antoine Béclère Hospital in Clamart. The women included in the survey will be taken a 20 ml blood sample and a cervical Pap smear before the invasive test (amniocentesis). The blood sample will be treated by the ISET method within 3 hours after collection and the filter will be stored at - 20°C. The cells obtained by Pap smear will be kept in an appropriate liquid and then treated by the ISET method in the Biochemistry Laboratory of Necker Hospital. The molecular analyses directed to the Trophoblastic cells for the NI-PND of Trisomy 21 will be performed in a blind study.
The instigators have planned to use the ISET method in a blind study including 100 cases of trisomy 21 and 300 control cases with normal caryotype. This study will allow to obtain results with sensitivity higher than 97 % and specificity higher than 99 % (IC 95 % [70-100]). The validation will be obtained by the opening of the blind study and the comparison of results obtained by the invasive method (amniocentesis) and the non-invasive method.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Necker Enfants Malades Hospital
Assistance Publique - Hôpitaux de Paris
Published on BioPortfolio: 2014-09-25T15:08:23-0400
The overall significance of this study is to develop a laboratory developed test (LDT) to use a new marker in the maternal blood to better identify pregnancies that have a child with a chr...
Combined first-trimester screening represents the gold standard of risk assessment for the presence of trisomy 21, 18, and 13. The concept is based on the age risk, the measurement of feta...
Demonstrate that the High output shotgun sequencing of the foetal DNA in the maternal blood could allow a complete discrimination between the mothers of a trisomic fetus 21 or a DISOMIQUE ...
The primary objectives of this study are to determine if rigosertib sodium, given orally in the form of soft gel capsules, is safe and is associated with a reduction in the number of blood...
The obstructive sleep apnea syndrome (OSAS) is frequently reported in subjects with trisomy 21. The consequences of this syndrome are expressed in various disorders such as cognitive and c...
Should active treatment be available for children with trisomy 18? In the Netherlands, trisomy 18 is described as a lethal condition leading to death during or immediately after birth. The Dutch cours...
Aneuploidy including trisomy results in developmental disabilities and is the leading cause of miscarriages in humans. Unlike trisomy 21, pathogenic mechanisms of trisomy 18 remain unclear. Here, we s...
The morphologic features of embryos with full trisomy 15 are described.
Common fetal aneuploidies include Down syndrome (trisomy 21 or T21), Edward syndrome (trisomy 18 or T18), Patau syndrome (trisomy 13 or T13), Turner syndrome (45,X), Klinefelter syndrome (47,XXY), Tri...
Trisomy 13 is a chromosomal disorder that occurs in complete or partial mosaic forms. It is characterized by central apnea, mental retardation, seizure and congenital heart disease. The survival of th...
The fraction of a blood sample, following CENTRIFUGATION, that is distinguished as a thin light-colored layer between the RED BLOOD CELLS, underneath it, and the PLASMA, above it. It is composed mostly of WHITE BLOOD CELLS and PLATELETS.
The number of RED BLOOD CELLS per unit volume in a sample of venous BLOOD.
The number of LEUKOCYTES and ERYTHROCYTES per unit volume in a sample of venous BLOOD. A complete blood count (CBC) also includes measurement of the HEMOGLOBIN; HEMATOCRIT; and ERYTHROCYTE INDICES.
The taking of a blood sample to determine its character as a whole, to identify levels of its component cells, chemicals, gases, or other constituents, to perform pathological examination, etc.
The analysis of a chemical substance by inserting a sample into a carrier stream of reagent using a sample injection valve that propels the sample downstream where mixing occurs in a coiled tube, then passes into a flow-through detector and a recorder or other data handling device.
Radiology is the branch of medicine that studies imaging of the body; X-ray (basic, angiography, barium swallows), ultrasound, MRI, CT and PET. These imaging techniques can be used to diagnose, but also to treat a range of conditions, by allowing visuali...
Women's Health - key topics include breast cancer, pregnancy, menopause, stroke Follow and track Women's Health News on BioPortfolio: Women's Health News RSS Women'...