Non-invasive prenatal testing of pregnancies at risk for phenylketonuria

Duan, Huikun; Ning, Liu; Zhao, Zhenhua; Wang, Yin; Li, Zhifeng; Xu, Mengnan; Cram, David S.; Kong, Xiangdong

doi:10.1136/archdischild-2017-313929

Cited by 25 publications

(22 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to previous studies that focused on hot‐spot PAH familial mutations, we were able to successfully develop and clinically validate a more comprehensive cSMART‐based NIPT genotyping assay for PKU. The high‐density primer sets that we designed ensured the efficient and uniform amplification of the exonic and immediate intronic splicing regions, where >95% of the known PAH gene mutations lie.…”

Section: Discussionmentioning

confidence: 90%

“…Approximately 4 ml of plasma was separated by two rounds of centrifugation and cfDNA was extracted using the QIAamp Circulating Nucleic Acid Kit (Qiagen, Hilden, Germany) (Figure A, I). Data analyses were carried out as originally described, with minor modifications (Figure ) . In brief, a pre‐library was prepared by end ligation of cfDNA fragments with fully degenerative barcode adapters (5´NNNNNNN3´) and a 15‐cycle PCR amplification step (Figure A, II).…”

Section: Methodsmentioning

confidence: 99%

“…In previous studies, we developed and validated circulating single‐molecule amplification and resequencing technology (cSMART) as a novel approach to quantitate the mutation load in pregnancy plasma, enabling fetal genotypes to be accurately deduced . More recently it was shown that cSMART could accurately genotype the fetus in pregnancies at risk for PKU; however, several limitations were noted, including using only primers to target the known parental mutations and the sole reliance of the plasma DNA mutation ratio to call fetal genotypes …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Noninvasive fetal genotyping in pregnancies at risk for PKU using a comprehensive quantitative cSMART assay for PAH gene mutations: a clinical feasibility study

Wei

et al. 2019

BJOG

View full text Add to dashboard Cite

Objective To assess the diagnostic performance of a novel circulating single molecule amplification and re‐sequencing technology (cSMART) method for noninvasive prenatal testing (NIPT) of Phenylketonuria (PKU). Design Blinded NIPT analysis of pregnancies at high risk for PKU. Setting Shanghai Xinhua Hospital and Hunan Jiahui Genetics Hospital, China. Population Couples (n = 33) with a child diagnosed with PKU. Methods Trio testing for pathogenic PAH mutations was performed by Sanger sequencing. In second pregnancies, invasive prenatal diagnosis (IPD) was used to determine fetal genotypes. NIPT was performed using a PAH gene‐specific cSMART assay. Based on the plasma DNA mutation ratio relative to the fetal DNA fraction, fetal genotypes were assigned using a maximum‐likelihood algorithm. Main outcome measures Concordance of fetal genotyping results between IPD and NIPT, and the sensitivity and specificity of the NIPT assay. Results Compared with gold standard IPD results, 32 of 33 fetuses (96.97%) were accurately genotyped by NIPT. The sensitivity and specificity of the NIPT assay was 100.00% (95% CI 59.04–100.00%) and 96.15% (95% CI 80.36–99.90%), respectively. Conclusions The novel cSMART assay demonstrated high accuracy for correctly calling fetal genotypes. We propose that this test has useful clinical utility for the rapid screening of high‐risk and low‐risk pregnancies with a known history of PKU on one or both sides of the family. Tweetable abstract NIPT of couples at high risk for PKU using a full‐coverage cSMART PAH gene test.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Noninvasive fetal genotyping in pregnancies at risk for PKU using a comprehensive quantitative cSMART assay for PAH gene mutations: a clinical feasibility study

Wei

et al. 2019

BJOG

View full text Add to dashboard Cite

show abstract

“…The study by Duan et al 1 demonstrates the use of NIPT to screen pregnancies at high risk of phenylketonuria. This has great potential to benefit families by allowing tailored care right from the start for children who would otherwise be at risk of severe disability due to untreated phenylketonuria, and in facilitating reproductive choice.…”

Section: Limitations Of Nipt/nipdmentioning

confidence: 99%

“…This avoids the miscarriage risk associated with invasive prenatal tests and can also be performed at an earlier stage of gestation. The paper by Duan et al 1 demonstrates the great potential benefits of this new technology for families affected by genetic conditions.…”

mentioning

confidence: 99%

Extending non-invasive prenatal testing to non-invasive prenatal diagnosis

Horton

2018

Arch Dis Child Fetal Neonatal Ed

View full text Add to dashboard Cite

Noninvasive prenatal prediction of fetal haplotype with Spearman rank correlation analysis model

Sun

Chen

et al. 2022

Molec Gen & Gen Med

View full text Add to dashboard Cite

Background Noninvasive prenatal testing (NIPT) has been widely used clinically to detect fetal chromosomal aneuploidy with high accuracy rates, gradually replacing traditional serological screening. However, the application of NIPT for monogenic diseases is still in an immature stage of exploration. The detection of mutations in peripheral blood of pregnant women requires precise qualitative and quantitative techniques, which limits its application. The bioinformatic strategies based on the SNP (single nucleotide polymorphism) linkage analysis are more practical, which can be divided into two types depending on whether proband information is needed. Hidden Markov Mode (HMM) and Sequential probability ratio test (SPRT) are suitable for families with probands. In contrast, methods based on databases and population demographic information are suitable for families without probands. Methods In this study, we proposed a Spearman rank correlation analysis method to infer the fetal haplotypes based on core family information. Allele frequencies of SNPs that were used to construct parental haplotypes were calculated as sets of nonparametric variables, in contrast to their theoretical values represented by a fetal fraction (FF). The effects on the calculation of the fetal concentration of two DNA enrichment methods, multiple‐PCR amplification, and targeted hybrid capture, were compared, and the heterozygosity distribution of SNPs within pedigrees was analyzed to reveal the best conditions for the model application. Results Predictions of the paternal haplotype inheritance were in line with expectations for both DNA library construction methods, while for maternal haplotype inheritance prediction, the rates were 96.55% for method multiple‐PCR amplification and 95.8% for method targeted hybrid capture. Conclusion Positive prediction rates showed that the maternal haplotype prediction was not as accurate as paternal one, due to the large amount of maternal noise in the mother's peripheral blood. Although this model is relatively immature, it provides a new perspective for noninvasive prenatal clinical tests of monogenic diseases.

show abstract

Non-invasive prenatal testing of pregnancies at risk for phenylketonuria

Abstract: The NIPT cSMART PKU assay was highly sensitive and specific for mutation detection and correct assignment of fetal genotypes. Based on comprehensive mutation coverage across the gene, the assay may initially have clinical utility as a pregnancy screening test for high-risk carrier couples.

Cited by 25 publications

References 18 publications

Noninvasive fetal genotyping in pregnancies at risk for PKU using a comprehensive quantitative cSMART assay for PAH gene mutations: a clinical feasibility study

Noninvasive fetal genotyping in pregnancies at risk for PKU using a comprehensive quantitative cSMART assay for PAH gene mutations: a clinical feasibility study

Extending non-invasive prenatal testing to non-invasive prenatal diagnosis

Noninvasive prenatal prediction of fetal haplotype with Spearman rank correlation analysis model

Contact Info

Product

Resources

About