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.
Keywords:
FGFR3; achondroplasia; noninvasive prenatal testing; thanatophoric dysplasia.
© 2018 Japanese Teratology Society.
MeSH terms
-
Achondroplasia / blood
-
Achondroplasia / diagnostic imaging
-
Achondroplasia / genetics*
-
Achondroplasia / pathology
-
Adult
-
Base Sequence
-
Biomarkers / blood
-
Cell-Free Nucleic Acids / blood
-
Cell-Free Nucleic Acids / genetics*
-
Diagnosis, Differential
-
Female
-
Fetal Growth Retardation / blood
-
Fetal Growth Retardation / diagnostic imaging
-
Fetal Growth Retardation / genetics*
-
Fetal Growth Retardation / 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
-
Receptor, Fibroblast Growth Factor, Type 3 / genetics*
-
Thanatophoric Dysplasia / blood
-
Thanatophoric Dysplasia / diagnostic imaging
-
Thanatophoric Dysplasia / genetics*
-
Thanatophoric Dysplasia / pathology
-
Tomography, X-Ray Computed
-
Ultrasonography
Substances
-
Biomarkers
-
Cell-Free Nucleic Acids
-
FGFR3 protein, human
-
Receptor, Fibroblast Growth Factor, Type 3
Grants and funding
-
15H04710/grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan
-
16K11117/grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan
-
H27-nanchitou (nan)-ippan-024/Ministry of Health, Labour and Welfare, Japan
-
Ogyaa Donation Foundation from the Japan Association of Obstetricians and Gynecologists