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- Title
Noninvasive fetal genotyping in pregnancies at risk for PKU using a comprehensive quantitative cSMART assay for PAH gene mutations: a clinical feasibility study.
- Authors
Lv, W; Li, Z; Wei, X; Zhu, H; Teng, Y; Zhou, M; Gong, Y; Cram, DS; Liang, D; Han, L; Wu, L; Cram, D S
- Abstract
<bold>Objective: </bold>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).<bold>Design: </bold>Blinded NIPT analysis of pregnancies at high risk for PKU.<bold>Setting: </bold>Shanghai Xinhua Hospital and Hunan Jiahui Genetics Hospital, China.<bold>Population: </bold>Couples (n = 33) with a child diagnosed with PKU.<bold>Methods: </bold>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.<bold>Main Outcome Measures: </bold>Concordance of fetal genotyping results between IPD and NIPT, and the sensitivity and specificity of the NIPT assay.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.<bold>Tweetable Abstract: </bold>NIPT of couples at high risk for PKU using a full-coverage cSMART PAH gene test.
- Subjects
CHINA; HIGH-risk pregnancy; INVASIVE diagnosis; SINGLE molecules; PRENATAL diagnosis; FEASIBILITY studies; COMPARATIVE studies; DNA; LONGITUDINAL method; RESEARCH methodology; MEDICAL cooperation; PHENYLKETONURIA; PREGNANCY complications; SECOND trimester of pregnancy; RESEARCH; RESEARCH funding; EVALUATION research; SEQUENCE analysis; GENOTYPES
- Publication
BJOG: An International Journal of Obstetrics & Gynaecology, 2019, Vol 126, Issue 12, p1466
- ISSN
1470-0328
- Publication type
journal article
- DOI
10.1111/1471-0528.15869