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

Abstract

Mutation analysis of the fibroblast growth factor receptor 3 gene in fetuses with thanatophoric dysplasia, type I Q.C. Wu, W.B. Wang, L. Sun, Y.S. Xu, X.J. Xie, X.M. Ma, Z.Y. Su Prenatal Diagnosis Center of Xiamen’s Maternal & Child Health Care Hospital, Xiamen City, Fujian Province (China) Summary 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 dwarfismdetected by antenatal ultrasonography were referred to this center. Before the termination of pregnancy, cordocentesis was per- formed for FGFR3 gene-sequencing analysis. Postmortem radiographic examination was performed in each instance for definitive di- agnosis. 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 phe- notypes among FGFR3-related skeletal dysplasias. Key words: Thanatophoric dysplasia; FGFR3 gene; Mutation; Prenatal diagnosis.