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Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia


ACHONDROPLASIA, the most common cause of chondrodysplasia in man (1 in 15,000 live births), is a condition of unknown origin characterized by short-limbed dwarfism and macrocephaly1,2. More than 90% of cases are sporadic and there is an increased paternal age at the time of conception of affected individuals, suggesting that de novo mutations are of paternal origin. Affected individuals are fertile and achondroplasia is transmitted as a fully penetrant autosomal dominant trait, accounting for rare familial forms of the disease (l0%))3–6. In contrast, homozygous achondroplasia is usually lethal in the neonatal period and affects 25% of the offspring of matings between heterozygous achondroplasia parents. The gene responsible for achondroplasia has been mapped to chromosome 4pl6.3 (refs 7, 8); the genetic interval encompassing the disease gene contains a member of the fibroblast-growth-factor receptor (FGFR3) family which is expressed in articular chondrocytes. Here we report the finding of recurrent missense mutations in a CpG doublet of the transmembrane domain of the FGFR3 protein (glycine substituted with arginine at residue 380, G380R) in 17 sporadic cases and 6 unrelated familial forms of achondroplasia. We show that the mutant genotype segregates with the disease in these families. Thus it appears that recurrent mutations of a single amino acid in the transmembrane domain of the FGFR3 protein account for all cases (23/23) of achondroplasia in our series.

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  1. Maroteaux, P. & Lamy, M. Clin. Orthop. 33, 91–103 (1964).

    Article  CAS  Google Scholar 

  2. Oberklaid, F., Danks, D. M., Jensen, F., Stace, I. & Rosshandler, S. J. med. Genet. 16, 140–146 (1979).

    Article  CAS  Google Scholar 

  3. Murdoch, J. L. et al. Ann. hum. Genet. 33, 227–244 (1970).

    Article  CAS  Google Scholar 

  4. Orioli, I. M., Castilla, E. E. & Barbosa-Neto, J. G. J. med. Genet. 23, 328–332 (1986).

    Article  CAS  Google Scholar 

  5. Stoll, C., Dott, B., Roth, M. P. & Alembik, Y. Clin. Genet. 35, 88–92 (1989).

    Article  CAS  Google Scholar 

  6. Gardner, R. J. M. Clin. Genet. 11, 31–38 (1977).

    Article  CAS  Google Scholar 

  7. Le Merrer, M. et al. Nature Genet. 6, 318–321 (1994).

    Article  CAS  Google Scholar 

  8. Velinov, M. et al. Nature Genet. 6, 314–317 (1994).

    Article  CAS  Google Scholar 

  9. Stanescu, R., Stanescu, V. & Maroteaux, P. Am. J. med. Genet. 37, 412–421 (1990).

    Article  CAS  Google Scholar 

  10. Thompson, L. et al. Genomics 11, 1133–1142 (1991).

    Article  CAS  Google Scholar 

  11. Ullrich, A. & Schlessinger, J. Cell 61, 203–212 (1990).

    Article  CAS  Google Scholar 

  12. Keegan, K., Johnson, D., Williams, L. T. & Hayman, M. J. Proc. natn. Acad. Sci. U.S.A. 88, 1095–1099 (1991).

    Article  ADS  CAS  Google Scholar 

  13. Kato, Y. & Iwamoto, M. J. biol. Chem. 265, 5903–5909 (1990).

    CAS  PubMed  Google Scholar 

  14. Iwamoto, M., Shimazu, A., Nakashima, K., Suzuki, F. & Kato, Y. J. biol. Chem. 266, 461–467 (1991).

    CAS  PubMed  Google Scholar 

  15. Ornitz, D. M. & Leder, P. J. biol. Chem. 267, 16305–16311 (1992).

    CAS  PubMed  Google Scholar 

  16. Pasquale, E. B. Proc. natn. Acad. Sci. U.S.A. 87, 5812–5816 (1990).

    Article  ADS  CAS  Google Scholar 

  17. Williams, L. T. Science 243, 1564–1570 (1989).

    Article  ADS  CAS  Google Scholar 

  18. Edery, P. et al. Nature 367, 378–380 (1994).

    Article  ADS  CAS  Google Scholar 

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Rousseau, F., Bonaventure, J., Legeai-Mallet, L. et al. Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. Nature 371, 252–254 (1994).

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