Non-invasive prenatal diagnosis of paternally inherited disorders from maternal plasma: detection of NF1 and CFTR mutations using droplet digital PCR.
Clin Chem Lab Med
; 56(5): 728-738, 2018 04 25.
Article
em En
| MEDLINE
| ID: mdl-29613853
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Diagnóstico Pré-Natal
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Reação em Cadeia da Polimerase
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Neurofibromatose 1
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Regulador de Condutância Transmembrana em Fibrose Cística
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Transtornos do Neurodesenvolvimento
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Mutação
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
França