A further mutation of the FGFR2 tyrosine kinase domain in mild Crouzon syndrome (original) (raw)

European Journal of Human Genetics volume 13, pages 503–505 (2005)Cite this article

Abstract

We report a family heterozygous for a newly identified mutation in the tyrosine kinase I domain of the FGFR2 gene (1576A>G, encoding the missense substitution Lys526Glu), associated with variable expressivity of Crouzon syndrome, including clinical nonpenetrance. Our observations expand both the clinical and molecular spectrum of this unusual subset of FGFR2 mutations.

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References

  1. Cohen Jr MM, Kreiborg S : Birth prevalence studies of the Crouzon syndrome: comparison of direct and indirect methods. Clin Genet 1992; 41: 12–15.
    Article Google Scholar
  2. Murdoch-Kinch CA, Ward RE : Metacarpophalangeal analysis in Crouzon syndrome: additional evidence for phenotypic convergence with the acrocephalosyndactyly syndromes. Am J Med Genet 1997; 73: 61–66.
    Article CAS Google Scholar
  3. Wilkie AOM, Patey SJ, Kan S-h, van den Ouweland AMW, Hamel BCJ : FGFs, their receptors, and human limb malformations: clinical and molecular correlations. Am J Med Genet 2002; 112: 266–278.
    Article Google Scholar
  4. Reardon W, Winter RM, Rutland P, Pulleyn LJ, Jones BM, Malcolm S : Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome. Nat Genet 1994; 8: 98–103.
    Article CAS Google Scholar
  5. Jabs EW, Li X, Scott AF et al: Jackson–Weiss and Crouzon syndromes are allelic with mutations in fibroblast growth factor receptor 2. Nat Genet 1994; 8: 275–279.
    Article CAS Google Scholar
  6. Muenke M, Wilkie AOM : Craniosynostosis syndromes; in: Scriver CR, Beaudet AL, Sly WS, Valle D (eds). The Metabolic and Molecular Bases of Inherited Disease, 8th edn. New York: McGraw-Hill, 2000, pp 6117–6146.
    Google Scholar
  7. Kan S-h, Elanko N, Johnson D et al: Genomic screening of fibroblast growth-factor receptor 2 reveals a wide spectrum of mutations in patients with syndromic craniosynostosis. Am J Hum Genet 2002; 70: 472–486.
    Article CAS Google Scholar
  8. Coulier F, Pontarotti P, Roubin R, Hartung H, Goldfarb M, Birnbaum D : Of worms and men: an evolutionary perspective on the fibroblast growth factor (FGF) and FGF receptor families. J Mol Evol 1997; 44: 43–56.
    Article CAS Google Scholar
  9. Mohammadi M, Schlessinger J, Hubbard SR : Structure of the FGF receptor tyrosine kinase domain reveals a novel autoinhibitory mechanism. Cell 1996; 86: 577–587.
    Article CAS Google Scholar
  10. El Ghouzzi V, Heuertz S, Bonaventure J et al: Mutation analysis in Crouzon and Pfeiffer syndromes identifies novel substitutions in the tyrosine kinase regions of the fibroblast growth factor receptor-2 (FGFR-2). Eur J Hum Genet 2002; 10 (Suppl 1): 247.
    Google Scholar
  11. Kan SH : Molecular genetics of human limb malformations: HOX genes and FGF pathways; DPhil Thesis, University of Oxford, 2003.
  12. Neilson KM, Friesel RE : Constitutive activation of fibroblast growth factor receptor-2 by a point mutation associated with Crouzon syndrome. J Biol Chem 1995; 270: 26037–26040.
    Article CAS Google Scholar
  13. Robertson SC, Meyer AN, Hart KC, Galvin BD, Webster MK, Donoghue DJ : Activating mutations in the extracellular domain of the fibroblast growth factor receptor 2 function by disruption of the disulfide bond in the third immunoglobulin-like domain. Proc Natl Acad Sci USA 1998; 95: 4567–4572.
    Article CAS Google Scholar
  14. Oldridge M, Lunt PW, Zackai EH et al: Genotype–phenotype correlation for nucleotide substitutions in the IgII–IgIII linker of FGFR2. Hum Mol Genet 1997; 6: 137–143.
    Article CAS Google Scholar
  15. Everett ET, Britto DA, Ward RE, Hartsfield JK : A novel FGFR2 gene mutation in Crouzon syndrome associated with apparent nonpenetrance. Cleft Palate Craniofac J 1999; 36: 533–541.
    Article CAS Google Scholar
  16. Johnson D, Wall SA, Mann S, Wilkie AOM : A novel mutation, Ala315Ser, in FGFR2: a gene–environment interaction leading to craniosynostosis? Eur J Hum Genet 2000; 8: 571–577.
    Article CAS Google Scholar

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Acknowledgements

We thank the family for their help with this study, and the Wellcome Trust for financial support (AOMW).

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Authors and Affiliations

  1. Center for Human Genetics, UZ Gasthuisberg, KU Leuven, Leuven, Belgium
    Thomy J L de Ravel & Jean-Pierre Fryns
  2. NDCLS, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford, UK
    Indira B Taylor & Andrew O M Wilkie
  3. Family Practitioner, Peer, Belgium
    Alex J T Van Oostveldt

Authors

  1. Thomy J L de Ravel
  2. Indira B Taylor
  3. Alex J T Van Oostveldt
  4. Jean-Pierre Fryns
  5. Andrew O M Wilkie

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Correspondence toAndrew O M Wilkie.

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de Ravel, T., Taylor, I., Van Oostveldt, A. et al. A further mutation of the FGFR2 tyrosine kinase domain in mild Crouzon syndrome.Eur J Hum Genet 13, 503–505 (2005). https://doi.org/10.1038/sj.ejhg.5201325

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