Prenatal diagnosis of thanatophoric dysplasia by mutational analysis of the fibroblast growth factor receptor 3 gene and a proposed correction of previously published PCR results

Thanatophoric dysplasia (TD) is the most frequent form of neonatal lethal s keletal dysplasia. Recently, mutations in the fibroblast growth factor rece ptor 3 (FGFR3) gene that cause two subtypes of this disorder, type I (TDI) and type II (TDII), have been identified. This discovery has now made it po ssible to make a definite diagnosis of TD by molecular methods. To date, pr enatal diagnosis of TD has been accomplished by ultrasonography in the seco nd trimester. However, it is not always possible to distinguish TD fetuses in utero from the other osteochondrodysplasias by ultrasonography or radiog raphy. We report on the prenatal diagnosis of a TD fetus, showing severe sh ortness of limbs and polyhydramnios, by identification of a mutation in the FGFR3 gene. Genomic DNA was isolated from the amniotic fluid and then subj ected to PCR amplification. The common TDI mutation, C --> T transition at nucleotide 742 in the FGFR3 gene, was identified using restriction enzyme a nalysis. This information was critical in obstetric management decisions la ter in pregnancy. However, although the mutation responsible for TDI was de tected previously, we noticed some inconsistencies in the published PCR res ults and have proposed a correction. Copyright (C) 1999 John Wiley & Sons, Ltd.