European Journal of Pediatrics

, Volume 154, Issue 3, pp 215–219 | Cite as

A glycine 375-to-cysteine substitution in the transmembrane domain of the fibroblast growth factor receptor-3 in a newborn with achondroplasia

  • A. Superti-Furga
  • B. Steinmann
  • R. Gitzelmann
  • G. Eich
  • A. Giedion
  • H. U. Bucher
  • J. Wisser
  • A. Superti-Furga
Medical Genetics Original Paper


Achondroplasia, the most common form of chondrodysplasia, has been associated with mutations in the gene of the fibroblast growth factor receptor-3 (FGFR-3) on chromosome 4p. All 39 achondroplasia alleles studied so far carried point mutations which caused the same amino acid exchange, a substitution of glycine by arginine at position 380 (G380R) in the transmembrane domain of the receptor. We report on a newborn with achondroplasia who does not carry a G380R mutation but has a mutation causing substitution of a nearby glycine with a cysteine (G375C). This observation indicates allelic heterogeneity and confirms the role of mutations in the transmembrane domain of FGFR-3 in the pathogenesis of achondroplasia.

Key words

Chondrodysplasia Dominant mutation Amino acid substitution Allelic heterogeneity 



fibroblast growth factor receptor-3


guanosine-to-adenosine transition


guanosine-to-cytidine transversion


guanosine-to-thymidine transversion


glycine-to-cysteine substitution at position 375


glycine-to-arginine substitution at position 380


polymerase chain reaction


single-strand conformation polymorphism


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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • A. Superti-Furga
    • 1
  • B. Steinmann
    • 1
  • R. Gitzelmann
    • 1
  • G. Eich
    • 2
  • A. Giedion
    • 2
  • H. U. Bucher
    • 3
  • J. Wisser
    • 4
  • A. Superti-Furga
    • 5
  1. 1.Division of Metabolism, Department of PediatricsUniversity of ZurichSwitzerland
  2. 2.Division of Radiology, Department of PediatricsUniversity of ZurichSwitzerland
  3. 3.Division of Neonatology, Department of PediatricsUniversity of ZurichSwitzerland
  4. 4.Department of ObstetricsUniversity of ZurichSwitzerland
  5. 5.University Children's HospitalZurichSwitzerland

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