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
en 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diagnóstico Prenatal
/
Reacción en Cadena de la Polimerasa
/
Neurofibromatosis 1
/
Regulador de Conductancia de Transmembrana de Fibrosis Quística
/
Trastornos del Neurodesarrollo
/
Mutación
Tipo de estudio:
Diagnostic_studies
/
Guideline
/
Screening_studies
Límite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Clin Chem Lab Med
Asunto de la revista:
QUIMICA CLINICA
/
TECNICAS E PROCEDIMENTOS DE LABORATORIO
Año:
2018
Tipo del documento:
Article
País de afiliación:
Francia