Achondroplasia is defined by recurrent G380R mutations of FGFR3

Am J Hum Genet. 1995 Feb;56(2):368-73.


Genomic DNA from 154 unrelated individuals with achondroplasia was evaluated for mutations in the fibroblast growth factor receptor 3 (FGFR3) transmembrane domain. All but one, an atypical case, were found to have a glycine-to-arginine substitution at codon 380. Of these, 150 had a G-to-A transition at nt 1138, and 3 had a G-to-C transversion at this same position. On the basis of estimates of the prevalence of achondroplasia, the mutation rate at the FGFR3 1138 guanosine nucleotide is two to three orders of magnitude higher than that previously reported for tranversions and transitions in CpG dinucleotides. To date, this represents the most mutable single nucleotide reported in the human genome. The homogeneity of mutations in achondroplasia is unprecedented for an autosomal dominant disorder and may explain the relative lack of heterogeneity in the achondroplasia phenotype.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Achondroplasia / genetics*
  • Amino Acid Sequence
  • Arginine / genetics
  • Base Sequence
  • Fibroblast Growth Factors / metabolism
  • Glycine / genetics
  • Humans
  • Molecular Sequence Data
  • Point Mutation*
  • Polymerase Chain Reaction
  • Protein-Tyrosine Kinases*
  • Receptor, Fibroblast Growth Factor, Type 3
  • Receptors, Fibroblast Growth Factor / genetics*
  • Sequence Analysis, DNA


  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factors
  • Arginine
  • FGFR3 protein, human
  • Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 3
  • Glycine

Associated data

  • GENBANK/S76733