Clinical outcomes of screen-positive genome-wide cfDNA cases for trisomy 20: results from the global expanded NIPT Consortium.

Trisomy 20 has been shown to be one of the most frequent rare autosomal trisomies in patients that undergo genome-wide noninvasive prenatal testing. Here, we describe the clinical outcomes of cases that screened positive for trisomy 20 following prenatal genome-wide cell-free (cf.) DNA screening.

Use of cell-free signals as biomarkers for early and easy prediction of preeclampsia.

Introduction: Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity worldwide. However, current methods of screening are complicated and require special skill sets. In this observational study of prospectively collected samples, we wanted to evaluate if cell-free () DNA could be an efficient biomarker for identification of at-risk patients.

Patient attitudes and preferences about expanded noninvasive prenatal testing.

Noninvasive prenatal testing (NIPT) using cell-free DNA (cfDNA) is typically carried out to screen for common fetal chromosomal anomalies, with the option to screen for a wider range of chromosomal changes (expanded NIPT) becoming increasingly available. However, little is known about pregnant patients' attitudes and preferences regarding expanded NIPT. To address this gap, we surveyed general-risk patients having first-tier cfDNA screening at a private prenatal clinic on their expectations for expanded NIPT.

A Collaborative Model to Implement Flexible, Accessible and Efficient Oncogenetic Services for Hereditary Breast and Ovarian Cancer: The C-MOnGene Study.

Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a collaborative oncogenetic model was recently developed and implemented at the CHU de Québec-Université Laval; Quebec; Canada. Here, we present the protocol of the C-MOnGene (Collaborative Model in OncoGenetics) study, funded to examine the context in which the model was implemented and document the lessons that can be learned to optimize the delivery of oncogenetic services.

Comparison of first-tier cell-free DNA screening for common aneuploidies with conventional publically funded screening.

Objective: This study evaluates the impact of offering cell-free DNA (cfDNA) screening as a first-tier test for trisomies 21 and 18.

Methods: This is a prospective study of pregnant women undergoing conventional prenatal screening who were offered cfDNA screening in the first trimester with clinical outcomes obtained on all pregnancies.

Results: A total of 1198 pregnant women were recruited.

Cell-Free DNA-Based Non-invasive Prenatal Screening for Common Aneuploidies in a Canadian Province: A Cost-Effectiveness Analysis.

Objective: Yearly, 450 000 pregnant Canadians are eligible for voluntary prenatal screening for trisomy 21. Different screening strategies select approximately 4% of women for invasive fetal chromosome testing. Non-invasive prenatal testing (NIPT) using maternal blood cell-free DNA could reduce those invasive procedures but is expensive.

Juvenile myelomonocytic leukemia-associated variants are associated with neo-natal lethal Noonan syndrome.

Gain-of-function variants in some RAS-MAPK pathway genes, including PTPN11 and NRAS, are associated with RASopathies and/or acquired hematological malignancies, most notably juvenile myelomonocytic leukemia (JMML). With rare exceptions, the spectrum of germline variants causing RASopathies does not overlap with the somatic variants identified in isolated JMML. Studies comparing these variants suggest a stronger gain-of-function activity in the JMML variants.

Non-invasive prenatal testing for fetal chromosome abnormalities: review of clinical and ethical issues.

Genomics-based non-invasive prenatal screening using cell-free DNA (cfDNA screening) was proposed to reduce the number of invasive procedures in current prenatal diagnosis for fetal aneuploidies. We review here the clinical and ethical issues of cfDNA screening. To date, it is not clear how cfDNA screening is going to impact the performances of clinical prenatal diagnosis and how it could be incorporated in real life.

Three new cases of terminal deletion of the long arm of chromosome 7 and literature review to correlate genotype and phenotype manifestations.

Partial monosomy of the long arm of chromosome 7 has been characterized by wide phenotypic manifestations, but holoprosencephaly (HPE) and sacral agenesis have frequently been associated with this chromosomal deletion. A clear relationship between genotype and phenotype remains to be defined in the 7q deletion syndrome. Three patients (1, 2, and 3) were investigated with 7q terminal deletion and compared with similar deletion cases in the literature in order to stratify the phenotypes associated with 7q35 and 7q36 terminal deletion patients.

Identification of trisomy 18, trisomy 13, and Down syndrome from maternal plasma.

Current prenatal diagnosis for fetal aneuploidies (including trisomy 21 [T21]) generally relies on an initial biochemical serum-based noninvasive prenatal testing (NIPT) after which women who are deemed to be at high risk are offered an invasive confirmatory test (amniocentesis or chorionic villi sampling for a fetal karyotype), which is associated with a risk of fetal miscarriage. Recently, genomics-based NIPT (gNIPT) was proposed for the analysis of fetal genomic DNA circulating in maternal blood. The diffusion of this technology in routine prenatal care could be a major breakthrough in prenatal diagnosis, since initial research studies suggest that this novel approach could be very effective and could reduce substantially the number of invasive procedures.

Cost-effectiveness of the management of rh-negative pregnant women.

Objective: The purpose of this study was to determine the most cost-effective option to prevent alloimmunization against the Rh factor.

Methods: A virtual population of Rh-negative pregnant women in Quebec was built to simulate the cost-effectiveness of preventing alloimmunization. The model considered four options: (1) systematic use of anti-D immunoglobulin; (2) fetal Rh(D) genotyping; (3) immunological determination of the father's Rh type; (4) mixed screening: immunological determination of the father's Rh type, followed if positive by fetal Rh(D) genotyping.

Recurrent anencephaly: a case report and examination of the VANGL1 and FOXN1 genes.

We report a new and rare case of recurrent anencephaly in a family with no other apparent abnormalities. The karyotypes of the family and all affected subjects were normal. Thorough mutational analyses of VANGL1 of chromosome 1p13.

Molecular prenatal diagnosis of a sporadic alobar holoprosencephalic fetus: genotype-phenotype correlations.

Objective: holoprosencephaly is the most common forebrain malformation syndrome with a multifactorial etiology. Currently, mutations are identified in 5-10% of non syndromic, non-chromosomal cases in at least 12 genes. We report the molecular prenatal diagnosis of a fetus with alobar holoprosencephaly.

Myoblasts derived from normal hESCs and dystrophic hiPSCs efficiently fuse with existing muscle fibers following transplantation.

Human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) have an endless self-renewal capacity and can theoretically differentiate into all types of lineages. They thus represent an unlimited source of cells for therapies of regenerative diseases, such as Duchenne muscular dystrophy (DMD), and for tissue repair in specific medical fields. However, at the moment, the low number of efficient specific lineage differentiation protocols compromises their use in regenerative medicine.

Holoprosencephaly-polydactyly (pseudotrisomy 13) syndrome: case report and diagnostic criteria.

We report a new case of a fetus with holoprosencephaly-polydactyly syndrome, also known as pseudo-trisomy 13 syndrome, and no other apparent abnormalities except for septal agenesis of the left lung. The fetal karyotype was normal. Mutational analysis of five genes (SHH, SIX3, TGIF, ZIC2, and GLI3), which are major genes associated with holoprosencephaly, did not disclose any mutational findings.

Midtrimester intra-amniotic sludge and the risk of spontaneous preterm birth.

We examined the association between midtrimester intra-amniotic sludge and spontaneous preterm birth (PTB) in asymptomatic women undergoing amniocentesis. We performed a prospective cohort study of women having an amniocentesis for fetal karyotyping between 14 and 24 weeks' gestation. Cervical length and the presence of amniotic sludge were assessed by transvaginal ultrasound.

Clinical validity of karyotyping for the diagnosis of chromosomal imbalance following array comparative genomic hybridisation.

Background: Array comparative genomic hybridisation (aCGH) represents a major advance in the ability to detect chromosomal imbalances (CI). A recent meta-analysis recommended aCGH for replacing karyotyping for patients with unexplained disabilities. However, favouring aCGH over karyotyping must be based on solid evidence due to the major implications of selecting a preferential diagnostic tool.

A survey of APC mutations in Quebec.

This is an 11-year survey of molecular analysis of APC germline mutations for the province of Quebec done at the Molecular Pathology Unit of the Jewish General Hospital which offers genetic testing for hereditary forms of colorectal cancer for the whole of Quebec province. We report on 47 unique mutations seen in 66 families affected with familial adenomatous polyposis. Of these unique mutations, 60% are short indels, 28% are point mutations, and 6% are whole exon deletions.

Cost-effectiveness and accuracy of prenatal Down syndrome screening strategies: should the combined test continue to be widely used?

Objective: We analyzed the cost-effectiveness (CE) and performances of commonly used prenatal Down syndrome (DS) screening strategies.

Study Design: We performed computer simulations to compare 8 screening options by applying empirical data from Serum, Urine, and Ultrasound Screening Study trials on the population of 110,948 pregnancies. Screening strategies outcomes, CE ratios, and incremental CE ratios were measured.

Current perspectives on the etiology of agnathia-otocephaly.

Agnathia-otocephaly, a rare, sporadic and lethal malformation, is characterized by microstomia (small mouth), aglossia (absence of the tongue), agnathia (absence of the lower jaw) and abnormally positioned ears. It is a principal anomaly derived from the first pharyngeal arch as a consequence of failed mesenchymal migration of the maxillary prominence and atrophy in the development of the mandibular prominences. Unfortunately, these patients have poor prognoses and may succumb to death shortly after birth due to respiratory problems if appropriate airway management is not implemented.

Rapid testing versus karyotyping in Down's syndrome screening: cost-effectiveness and detection of clinically significant chromosome abnormalities.

In all, 80% of antenatal karyotypes are generated by Down's syndrome screening programmes (DSSP). After a positive screening, women are offered prenatal foetus karyotyping, the gold standard. Reliable molecular methods for rapid aneuploidy diagnosis (RAD: fluorescence in situ hybridization (FISH) and quantitative fluorescence PCR (QF-PCR)) can detect common aneuploidies, and are faster and less expensive than karyotyping.

Prenatal diagnosis and molecular genetic studies on a new case of agnathia-otocephaly.

Otocephaly is a severe and lethal malformation. We report a new case of a fetus with agnathia-otocephaly, presenting only the facial findings but with otherwise normal organs. The fetal karyotype was normal.

In vitro and in vivo study of human amniotic fluid-derived stem cell differentiation into myogenic lineage.

Recent findings have shown that amniotic fluid (AF) could be a putative new source of multipotent stem cells (SC). We investigated whether these human SC could efficiently differentiate into myogenic lineage in vitro and integrate in vivo skeletal muscle in severe combined immunodeficiency (SCID) mice. C/kit immunomagnetic-sorted AF (AF c/kit+) SC were characterized by immunocytochemistry and Southern blotting for myogenic markers (desmin, MyoD).