Non-invasive fetal genotyping for maternal alleles with droplet digital PCR: A comparative study of analytical approaches.
Journal
Prenatal diagnosis
ISSN: 1097-0223
Titre abrégé: Prenat Diagn
Pays: England
ID NLM: 8106540
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
revised:
22
12
2022
received:
02
11
2022
accepted:
31
01
2023
medline:
18
4
2023
pubmed:
11
2
2023
entrez:
10
2
2023
Statut:
ppublish
Résumé
To develop a flexible droplet digital PCR (ddPCR) workflow to perform non-invasive prenatal diagnosis via relative mutation dosage (RMD) for maternal pathogenic variants with a range of inheritance patterns, and to compare the accuracy of multiple analytical approaches. Cell free DNA (cfDNA) was tested from 124 archived maternal plasma samples: 88 cases for sickle cell disease and 36 for rare Mendelian conditions. Three analytical methods were compared: sequential probability ratio testing (SPRT), Bayesian and z-score analyses. The SPRT, Bayesian and z-score analyses performed similarly well with correct prediction rates of 96%, 97% and 98%, respectively. However, there were high rates of inconclusive results for each cohort, particularly for z-score analysis which was 31% overall. Two samples were incorrectly classified by all three analytical methods; a false negative result predicted for a fetus affected with sickle cell disease and a false positive result predicting the presence of an X-linked IDS variant in an unaffected fetus. ddPCR can be applied to RMD for diverse conditions and inheritance patterns, but all methods carry a small risk of erroneous results. Further evaluation is required both to reduce the rate of inconclusive results and explore discordant results in more detail.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
477-488Subventions
Organisme : NIHR Biomedical Research Centre at Great Ormond Street Hospital
Organisme : National Institute for Health and Care Research
Informations de copyright
© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.
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