Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia

Cell. 1994 Jul 29;78(2):335-42. doi: 10.1016/0092-8674(94)90302-6.


Achondroplasia (ACH) is the most common genetic form of dwarfism. This disorder is inherited as an autosomal dominant trait, although the majority of cases are sporadic. A gene for ACH was recently localized to 4p16.3 by linkage analyses. The ACH candidate region includes the gene encoding fibroblast growth factor receptor 3 (FGFR3), which was originally considered as a candidate for the Huntington's disease gene. DNA studies revealed point mutations in the FGFR3 gene in ACH heterozygotes and homozygotes. The mutation on 15 of the 16 ACH-affected chromosomes was the same, a G-->A transition, at nucleotide 1138 of the cDNA. The mutation on the only ACH-affected chromosome 4 without the G-->A transition at nucleotide 1138 had a G-->C transversion at this same position. Both mutations result in the substitution of an arginine residue for a glycine at position 380 of the mature protein, which is in the transmembrane domain of FGFR3.

Publication types

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

MeSH terms

  • Achondroplasia / genetics*
  • Alleles
  • Amino Acid Sequence
  • B-Lymphocytes
  • Base Sequence
  • Cells, Cultured
  • Child
  • DNA Mutational Analysis
  • DNA, Complementary / biosynthesis
  • Female
  • Fibroblasts
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Molecular Sequence Data
  • Point Mutation / genetics*
  • Point Mutation / physiology
  • Polymorphism, Restriction Fragment Length
  • Protein-Tyrosine Kinases*
  • Receptor, Fibroblast Growth Factor, Type 3
  • Receptors, Fibroblast Growth Factor / genetics*


  • DNA, Complementary
  • Receptors, Fibroblast Growth Factor
  • FGFR3 protein, human
  • Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 3