Skeletal Dysplasia Caused by FGFR3 Mutation in Taiwanese Patients

Abstract

Background. The identification of a missense mutation (G380R) in the fibroblast growth factor receptor 3 (FGFR3) gene in patients with achondroplasia was followed by the detection of common FGFR3 mutations in two clinically related occurrences of skeletal dysplasia.: hypochondroplasia, and thanatophoric dysplasia. In this study, we investigated the FGFR3 mutation of achondroplasia, hypochondroplasia, and thanatophoric dysplasia in Taiwanese patients. Methods: There were 28 patients with achondroplasia, 18 with hypochondroplasia and two with thanatophoric dysplasia type I included in this study. Polymerase chain reaction (PCR), direct sequencing, and amplification created restriction site (ACRS) tests were performed to analyze the mutations on FGFR3 in these patients. Results: Genetic homogeneity of achondroplasia was demonstrated as recurrent G380R mutations in all patients hitherto reported. Although all detected mutations of hypochondroplasia were accounted for by a recurrent N540K mutation in the first tyrosine kinase domain of the receptor, a significant portion (45%) of our patients did not harbor the N540K mutation. Two patients with type I thanatophoric dysplasia were found to carry the R248C mutation. Conclusions: We used either a natural restriction enzyme site or ACRS to detect the recurrent G380R mutation of achondroplasia. The use of the ACRS was found to be more cost-effective and efficient than the use of the natural restriction enzyme digest.