Noninvasive prenatal test for FGFR3-related skeletal dysplasia based on next-generation sequencing and plasma cell-free DNA: Test performance analysis and feasibility exploration.
Prenat Diagn
; 38(11): 821-828, 2018 10.
Article
em En
| MEDLINE
| ID: mdl-30048571
ABSTRACT
OBJECTIVE:
To explore the feasibility and accuracy of a noninvasive prenatal test for fibroblast growth factor receptor 3 (FGFR3)-related skeletal dysplasia based on next-generation sequencing (NGS) of plasma cell-free DNA.METHOD:
Fragmented genome DNA (gDNA) of fetuses with achondroplasia (ACH) and thanatophoric dysplasia type I (TD I) was mixed with postdelivery maternal plasma cell-free DNA to generate spiked samples of different modeled fetal fractions. Multiplex polymerase chain reaction was used to amplify the 19 FGFR3 loci, and the amplification products were then sequenced by NGS to detect the fetal mutant alleles. Then, maternal plasma samples of pregnant women carrying ACH (n = 4) and TD I fetuses (n = 2), as well as healthy controls (n = 15), were tested by NGS, and the test performance was evaluated.RESULTS:
Fetal FGFR3 mutations were detected in all artificial mixtures with fetal gDNA concentrations above 3%. In clinical validation, our method identified all fetal FGFR3 mutant alleles from maternal plasma, with no false positive results. The sensitivity and specificity of our method were 100% (95% CI, 54.1%-100%) and 100% (78.2%-100%), respectively.CONCLUSION:
Our method had a favorable performance for noninvasively detecting fetal FGFR3 mutations in maternal plasma, highlighting its promising value in developing a noninvasive prenatal test for de novo and paternally inherited disorders.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Displasia Tanatofórica
/
Receptor Tipo 3 de Fator de Crescimento de Fibroblastos
/
Testes para Triagem do Soro Materno
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
Prenat Diagn
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China