Non-invasive prenatal detection of achondroplasia using circulating fetal DNA in maternal plasma.

PURPOSE: To perform a reliable non-invasive detection of the fetal achondroplasia using maternal plasma.

METHODS

We developed a quantitative fluorescent-polymerase chain reaction (QF-PCR) method suitable for detection of the FGFR3 mutation (G1138A) causing achondroplasia. This method was applied in a non-invasive detection of the fetal achondroplasia using circulating fetal-DNA (cf-DNA) in maternal plasma. Maternal plasmas were obtained at 27 weeks of gestational age from women carrying an achondroplasia fetus or a normal fetus.

RESULTS

Two percent or less achondroplasia DNA was reliably detected by QF-PCR. In a woman carrying a normal fetus, analysis of cf-DNA showed only one peak of the wild-type G allele. In a woman expected an achondroplasia fetus, analysis of cf-DNA showed the two peaks of wild-type G allele and mutant-type A allele and accurately detected the fetal achondroplasia.

CONCLUSIONS

The non-invasive method using maternal plasma and QF-PCR may be useful for diagnosis of the fetal achondroplasia.