Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3

Nat Genet. 1995 Mar;9(3):321-8. doi: 10.1038/ng0395-321.


Thanatophoric dysplasia (TD), the most common neonatal lethal skeletal dysplasia, affects one out of 20,000 live births. Affected individuals display features similar to those seen in homozygous achondroplasia. Mutations causing achondroplasia are in FGFR3, suggesting that mutations in this gene may cause TD. A sporadic mutation causing a Lys650Glu change in the tyrosine kinase domain of FGFR3 was found in 16 of 16 individuals with one type of TD. Of 39 individuals with a second type of TD, 22 had a mutation causing an Arg248Cys change and one had a Ser371Cys substitution, both in the extracellular region of the protein. None of these mutations were found in 50 controls showing that mutations affecting different functional domains of FGFR3 cause different forms of this lethal disorder.

Publication types

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

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Base Sequence
  • DNA / genetics
  • DNA Primers / genetics
  • Female
  • Femur / abnormalities
  • Femur / diagnostic imaging
  • Humans
  • Infant, Newborn
  • Male
  • Molecular Sequence Data
  • Pedigree
  • Point Mutation*
  • Polymerase Chain Reaction
  • Protein-Tyrosine Kinases*
  • Radiography
  • Receptor, Fibroblast Growth Factor, Type 3
  • Receptors, Fibroblast Growth Factor / genetics*
  • Skull / abnormalities
  • Skull / diagnostic imaging
  • Thanatophoric Dysplasia / classification
  • Thanatophoric Dysplasia / diagnostic imaging
  • Thanatophoric Dysplasia / genetics*


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