[Achondroplasia: molecular study of 28 patients]

Abstract

Background: The main goal of the study is to investigate in the Spanish population the value of searching for the Gly380Arg mutation in the transmembrane domain of fibroblast growth factor receptor-3 (FGFR3#) as the basis for the molecular diagnosis of achondroplasia.

Patients and methods: Twenty eight achondroplastic patients were studied. Genomic DNA obtained from blood was used to amplify using PCR a 164 bp segment of FGFR3 encompassing the transmembrane domain. The occurrence of the G-->A transition and of the G-->C transversion at the first base of codon 380 were investigated by digestion with the restriction enzymes Sfcl and Mspl followed by electrophoretic analysis of the products.

Results: All achondroplastic patients were found to be heterozygous for the Gly380Arg mutation, as a consequence of the G-->A transition in 27 cases and of the G-->C transversion in the remaining patient. None of these changes were found in control subjects including a hypochondroplastic patient.

Conclusions: The identification of the Gly380Arg mutation can be used in Spain for conclusive diagnosis of achondroplasia. The guanine at the first position of codon 380 of FGFR3 exhibits similarly increased frequency of mutation than in other populations, an thus it is unlikely that the genetic background of the population determines the mutation potential of this guanine.