Mutation analysis of the fibroblast growth factor receptor 3 gene in fetuses with thanatophoric dysplasia, type I

Abstract

Objective: To analyze the fibroblast growth factor receptor 3 gene (FGFR3) mutations in fetuses with thanatophoric dysplasia type I (TD1) and to provide additional data for genotype-phenotype analyses. Materials and Methods: Eight cases of severe fetal short-limb dwarfism detected by antenatal ultrasonography were referred to this center. Before the termination of pregnancy, cordocentesis was performed for FGFR3 gene-sequencing analysis. Postmortem radiographic examination was performed in each instance for definitive diagnosis. Results: By FGFR3 gene sequencing, the authors identified six cases with missense mutations and two cases with stop codon mutations in the FGFR3 gene. Among the 6 FGFR3 missense mutations, four cases revealed a heterozygous p.Arg248Cys mutation, one case had a heterozygous p. Tyr373Cys mutation, and one case had a heterozygous p.Ser348Cys mutation. Discussion: The present data confirm the existence of hotspot FGFR3 mutations of TD1 and suggest that considerable overlap may occur between genotypes and phenotypes among FGFR3-related skeletal dysplasias.