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 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 Diagnosis of Monogenic Diseases by Targeted Massively Parallel Sequencing of Maternal Plasma: Application to β-Thalassemia

2012 ◽  
Vol 58 (10) ◽  
pp. 1467-1475 ◽  
Author(s):  
Kwan-Wood G Lam ◽  
Peiyong Jiang ◽  
Gary J W Liao ◽  
K C Allen Chan ◽  
Tak Y Leung ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Massively Parallel Sequencing ◽  
Globin Gene ◽  
Maternal Plasma ◽  
Massively Parallel ◽  
Sequencing Data ◽  
Plasma Dna ◽  
Parallel Sequencing ◽  
Noninvasive Prenatal Diagnosis ◽  
Monogenic Diseases

Abstract BACKGROUND A genomewide genetic and mutational profile of a fetus was recently determined via deep sequencing of maternal plasma DNA. This technology could have important applications for noninvasive prenatal diagnosis (NIPD) of many monogenic diseases. Relative haplotype dosage (RHDO) analysis, a core step of this procedure, would allow one to elucidate the maternally inherited half of the fetal genome. For clinical applications, the cost and complexity of data analysis might be reduced via targeted application of this approach to selected genomic regions containing disease-causing genes. There is thus a need to explore the feasibility of performing RHDO analysis in a targeted manner. METHODS We performed target enrichment by using solution-phase hybridization followed by massively parallel sequencing of the β-globin gene region in 2 families undergoing prenatal diagnosis for β-thalassemia. We used digital PCR strategies to physically deduce parental haplotypes. Finally, we performed RHDO analysis with target-enriched sequencing data and parental haplotypes to reveal the β-thalassemic status for the fetuses. RESULTS A mean sequencing depth of 206-fold was achieved in the β-globin gene region by targeted sequencing of maternal plasma DNA. RHDO analysis was successful for the sequencing data obtained from the target-enriched samples, including a region in one of the families in which the parents had similar haplotype structures. Data analysis revealed that both fetuses were heterozygous carriers of β-thalassemia. CONCLUSIONS Targeted sequencing of maternal plasma DNA for NIPD of monogenic diseases is feasible.

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
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