Noninvasive prenatal diagnosis for pregnancies at risk for β-thalassaemia: a retrospective study.
Circulating single molecule amplification and re-sequencing technology
HBB gene
fetal genotyping
invasive prenatal diagnosis
noninvasive prenatal diagnosis
β-thalassaemia
Journal
BJOG : an international journal of obstetrics and gynaecology
ISSN: 1471-0528
Titre abrégé: BJOG
Pays: England
ID NLM: 100935741
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
accepted:
16
04
2020
pubmed:
5
5
2020
medline:
5
3
2021
entrez:
5
5
2020
Statut:
ppublish
Résumé
To evaluate the clinical feasibility of noninvasive prenatal diagnosis (NIPD) for β-thalassaemia using circulating single molecule amplification and re-sequencing technology (cSMART). Through carrier screening, 102 pregnant Chinese couples carrying pathogenic HBB gene variants were recruited to the study. Pregnancies were managed using traditional invasive prenatal diagnosis (IPD). Retrospectively, we evaluated the archived pregnancy plasma DNA by NIPD to evaluate the performance of our cSMART assay for fetal genotyping. Chinese prenatal diagnostic centres specialising in thalassaemia testing. Chinese carrier couples at high genetic risk for β-thalassaemia. Fetal cell sampling was performed by amniocentesis and HBB genotypes were determined by reverse dot blot. NIPD was performed by a newly designed HBB cSMART assay and fetal genotypes were called by measuring the allelic ratios in the maternal cell-free DNA. Concordance of HBB fetal genotyping between IPD and NIPD and the sensitivity and specificity of NIPD. Invasive prenatal diagnosis identified 29 affected homozygotes or compound heterozygotes, 54 heterozygotes and 19 normal homozygotes. Compared with IPD results, 99 of 102 fetuses (97%) were correctly genotyped by our NIPD assay. Two of three discordant samples were false positives and the other sample involved an incorrect call of a heterozygote carrier as a homozygote normal. Overall, the sensitivity and specificity of our NIPD assay was 100% (95% CI 88.06-100.00%) and 97.26% (95% CI 90.45-99.67%), respectively. This study demonstrates that our cSMART-based NIPD assay for β-thalassaemia has potential clinical utility as an alternative to IPD for pregnant HBB carrier couples. A new noninvasive test for pregnancies at risk for β-thalassaemia.
Identifiants
pubmed: 32363759
doi: 10.1111/1471-0528.16295
doi:
Substances chimiques
beta-Globins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
448-457Subventions
Organisme : National Natural Science Foundation of China
ID : 81501268
Organisme : National Natural Science Foundation of China
ID : 81771599
Organisme : "555 Talent plan" of Changsha High-tech Zone, Science-Health Foundation of Hunan Province
ID : 2018JJ6006
Organisme : National Key Research and Development Program of China
ID : 2017YFC1001802
Organisme : National Key Research and Development Program of China
ID : 2018YFC1002201
Organisme : Hunan Major Projects for Science and Technology Development
ID : 2019SK1014
Informations de copyright
© 2020 Royal College of Obstetricians and Gynaecologists.
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