scholarly journals Non-Invasive Prenatal Diagnosis of Lethal Skeletal Dysplasia by Targeted Capture Sequencing of Maternal Plasma

PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0159355 ◽  
Author(s):  
Shan Dan ◽  
Yuan Yuan ◽  
Yaoshen Wang ◽  
Chao Chen ◽  
Changxin Gao ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Skeletal Dysplasia ◽  
Maternal Plasma ◽  
Non Invasive ◽  
Targeted Capture ◽  
Lethal Skeletal Dysplasia ◽  
Capture Sequencing

scholarly journals Noninvasive prenatal test of methylmalonic academia cblC type through targeted sequencing of cell-free DNA in maternal plasma

2018 ◽  
Author(s):  
Lianshu Han ◽  
Chao Chen ◽  
Fengyu Guo ◽  
Jun Ye ◽  
Zhiyu Peng ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Maternal Plasma ◽  
Sequencing Data ◽  
Non Invasive ◽  
Invasive Test ◽  
Target Capture ◽  
Wild Allele ◽  
Prenatal Test ◽  
Targeted Capture ◽  
Cobalamin Metabolism

AbstractMethylmalonic acidemia (MMA) cblC type is the most frequent inborn error of intracellular cobalamin metabolism which is caused by mutations of MMACHC gene. Non-invasive test of MMA for pregnant women facilitates safe and timely prenatal diagnosis of the disease. In our study, we aimed to design and validate a haplotype-based noninvasive prenatal test (NIPT) method for cblC type of MMA. Targeted capture sequencing using customized hybridization was performed utilizing gDNA (genomic DNA) of trios including parents and an affected proband to determine parental haplotypes associated with the mutant and wild allele. The fetal haplotype was inferred later based on the high depth sequencing data of maternal plasma as well as haplotype linkage analysis. The fetal genotypes deduced by NIPT were further validated by amniocentesis. Haplotype-based NIPT was successfully performed in 21 families. The results of NIPT of 21 families were all consistent with invasive prenatal diagnosis, which was interpreted in a blinded fashion. Three fetuses were identified as compound heterozygosity of MMACHC, 9 fetuses were carriers of MMACHC variant, and 9 fetuses were normal. These results indicated that the haplotype-based NIPT for MMA through small target capture region sequencing is technically accurate and feasible.

scholarly journals Case report: targeted whole exome sequencing enables the first prenatal diagnosis of the lethal skeletal dysplasia Osteocraniostenosis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Lara Pemberton ◽  
Robert Barker ◽  
Anna Cockell ◽  
Vijaya Ramachandran ◽  
Andrea Haworth ◽  
...  
Keyword(s):  
Case Report ◽  
Prenatal Diagnosis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Skeletal Dysplasia ◽  
Genetic Disorder ◽  
Specific Gene ◽  
Ultrasound Images ◽  
Whole Exome ◽  
Lethal Skeletal Dysplasia

Abstract Background Osteocraniostenosis (OCS) is a rare genetic disorder characterised by premature closure of cranial sutures, gracile bones and perinatal lethality. Previously, diagnosis has only been possible postnatally on clinical and radiological features. This study describes the first prenatal diagnosis of OCS. Case presentation In this case prenatal ultrasound images were suggestive of a serious but non-lethal skeletal dysplasia. Due to the uncertain prognosis the parents were offered Whole Exome Sequencing (WES), which identified a specific gene mutation in the FAMIIIa gene. This mutation had previously been detected in two cases and was lethal in both perinatally. This established the diagnosis, a clear prognosis and allowed informed parental choice regarding ongoing pregnancy management. Conclusions This case report supports the use of targeted WES prenatally to confirm the underlying cause and prognosis of sonographically suspected abnormalities.

Non-invasive prenatal diagnosis using cell-free fetal DNA in maternal plasma from PGD pregnancies

2009 ◽  
Vol 19 (5) ◽  
pp. 714-720 ◽  
Author(s):  
Ying Li ◽  
Gheona Altarescu ◽  
Paul Renbaum ◽  
Talia Eldar-Geva ◽  
Ephrat Levy-Lahad ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Maternal Plasma ◽  
Non Invasive ◽  
Fetal Dna ◽  
Cell Free Fetal Dna

Non-invasive prenatal diagnosis of paternally inherited disorders from maternal plasma: detection of NF1 and CFTR mutations using droplet digital PCR

2018 ◽  
Vol 56 (5) ◽  
pp. 728-738 ◽  
Author(s):  
Aurélia Gruber ◽  
Mathilde Pacault ◽  
Laila Allach El Khattabi ◽  
Nicolas Vaucouleur ◽  
Lucie Orhant ◽  
...  
Keyword(s):  
At Risk ◽  
Prenatal Diagnosis ◽  
Digital Pcr ◽  
Maternal Plasma ◽  
Droplet Digital Pcr ◽  
Compound Heterozygous ◽  
Inherited Disorders ◽  
Non Invasive ◽  
Cell Free Fetal Dna ◽  
Monogenic Diseases

Abstract Background: To limit risks of miscarriages associated with invasive procedures of current prenatal diagnosis practice, we aim to develop a personalized medicine-based protocol for non-invasive prenatal diagnosis (NIPD) of monogenic disorders relying on the detection of paternally inherited mutations in maternal blood using droplet digital PCR (ddPCR). Methods: This study included four couples at risk of transmitting paternal neurofibromatosis type 1 (NF1) mutations and four couples at risk of transmitting compound heterozygous CFTR mutations. NIPD was performed between 8 and 15 weeks of gestation, in parallel to conventional invasive diagnosis. We designed specific hydrolysis probes to detect the paternal mutation and to assess the presence of cell-free fetal DNA by ddPCR. Analytical performances of each assay were determined from paternal sample, an then fetal genotype was inferred from maternal plasma sample. Results: Presence or absence of the paternal mutant allele was correctly determined in all the studied plasma DNA samples. Conclusions: We report an NIPD protocol suitable for implementation in an experienced laboratory of molecular genetics. Our proof-of-principle results point out a high accuracy for early detection of paternal NF1 and CFTR mutations in cell-free DNA, and open new perspectives for extending the technology to NIPD of many other monogenic diseases.

Use of maternal plasma for non-invasive prenatal diagnosis of fetal ABO genotypes

2007 ◽  
Vol 45 (8) ◽  
Author(s):  
Jin-Lai Meng ◽  
Xie-Tong Wang ◽  
Yu Wang ◽  
Ya-Fei Yue ◽  
Xin Wang ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Maternal Plasma ◽  
Non Invasive ◽  
Abo Genotypes

The SAFE project: towards non-invasive prenatal diagnosis

2009 ◽  
Vol 37 (2) ◽  
pp. 460-465 ◽  
Author(s):  
Deborah G. Maddocks ◽  
Medhat S. Alberry ◽  
George Attilakos ◽  
Tracey E. Madgett ◽  
Kin Choi ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Large Scale ◽  
Single Gene ◽  
Cost Effective ◽  
Maternal Plasma ◽  
Molecular Techniques ◽  
Maternal Circulation ◽  
Haemolytic Disease ◽  
Non Invasive ◽  
New Biomarkers

After the revolutionary detection of ffDNA (free fetal DNA) in maternal circulation by real-time PCR in 1997 and advances in molecular techniques, NIPD (non-invasive prenatal diagnosis) is now a clinical reality. Non-invasive diagnosis using ffDNA has been implemented, allowing the detection of paternally inherited alleles, sex-linked conditions and some single-gene disorders and is a viable indicator of predisposition to certain obstetric complications [e.g. PET (pre-eclampsia)]. To date, the major use of ffDNA genotyping in the clinic has been for the non-invasive detection of the pregnancies that are at risk of HDFN (haemolytic disease of the fetus and newborn). This has seen numerous clinical services arising across Europe and many large-scale NIPD genotyping studies taking place using maternal plasma. Because of the interest in performing NIPD and the speed at which the research in this area was developing, the SAFE (Special Non-Invasive Advances in Fetal and Neonatal Evaluation) NoE (Network of Excellence) was founded. The SAFE project was set up to implement routine, cost-effective NIPD and neonatal screening through the creation of long-term partnerships within and beyond the European Community and has played a major role in the standardization of non-invasive RHD genotyping. Other research using ffDNA has focused on the amount of ffDNA present in the maternal circulation, with a view to pre-empting various complications of pregnancy. One of the key areas of interest in the non-invasive arena is the prenatal detection of aneuploid pregnancies, particularly Down's syndrome. Owing to the high maternal DNA background, detection of ffDNA from maternal plasma is very difficult; consequently, research in this area is now more focused on ffRNA to produce new biomarkers.

Sign in / Sign up

Export Citation Format

Share Document