Multiplex PCR in noninvasive prenatal diagnosis for FGFR3-related disorders.

Abstract

Thanatophoric dysplasia and achondroplasia are allelic disorders caused by a constitutively active mutation in the FGFR3 gene. Because thanatophoric dysplasia is a lethal disorder and achondroplasia is non-lethal, they need to be distinguished after ultrasound identification of fetal growth retardation with short limbs. Accordingly, we have developed a noninvasive prenatal test using cell-free fetal DNA in the maternal circulation to distinguish thanatophoric dysplasia and achondroplasia. A multiplex PCR system encompassing five mutation hotspots in the FGFR3 gene allowed us to efficiently identify the responsible mutation in cell-free DNA in all examined pregnancies with a suspected thanatophoric dysplasia or achondroplasia fetus. This system will be helpful in the differential diagnosis of thanatophoric dysplasia and achondroplasia in early gestation and in couples concerned about the recurrence of thanatophoric dysplasia due to germinal mosaicism.

• Authors: Sumire Terasawa, Asuka Kato, Haruki Nishizawa, Takema Kato, Hikari Yoshizawa, Yoshiteru Noda, Jun Miyazaki, Mayuko Ito, Takao Sekiya, Takuma Fujii, Hiroki Kurahashi
• Journal: Congenital anomalies (Congenit Anom (Kyoto)) Vol. 59 Issue 1 Pg. 4-10 (Jan 2019) ISSN: 1741-4520 [Electronic] Australia
• PMID: 29542187 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2018 Japanese Teratology Society.

Chemical References

• Biomarkers
• Cell-Free Nucleic Acids
• FGFR3 protein, human
• Receptor, Fibroblast Growth Factor, Type 3

Topics

• Achondroplasia (blood, diagnostic imaging, genetics, pathology)
• Adult
• Base Sequence
• Biomarkers (blood)
• Cell-Free Nucleic Acids (blood, genetics)
• Diagnosis, Differential
• Female
• Fetal Growth Retardation (blood, diagnostic imaging, genetics, pathology)
• Fetus
• Gene Expression
• Humans
• Mosaicism
• Multiplex Polymerase Chain Reaction (methods)
• Mutation
• Pregnancy
• Pregnancy Trimester, Second
• Pregnancy Trimester, Third
• Prenatal Diagnosis (methods)
• Receptor, Fibroblast Growth Factor, Type 3 (blood, genetics)
• Thanatophoric Dysplasia (blood, diagnostic imaging, genetics, pathology)
• Tomography, X-Ray Computed
• Ultrasonography