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A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia

Nature Genetics volume 10, pages 357–359 (1995)Cite this article

Abstract

Hypochondroplasia (MIM 146000) is an autosomal dominant skeletal dysplasia with skeletal features similar to but milder than those seen in achondroplasia1–4. Within the past year, the achondroplasia locus has been mapped to 4p16.3 (refs 5–7) and mutations in the fibroblast growth factor receptor 3 (FGFR3) gene have been identified in patients with the disorder8,9. More than 95% of 242 cases reported so far are accounted for by a single Gly380Arg mutation8–11. McKusick et al.12 proposed that achondroplasia and hypochondroplasia are allelic based on the similarities in phenotype between the two disorders and the identification of a severely dwarfed individual whose father had achondroplasia and whose mother had hypochondroplasia. There is also genetic linkage evidence that hypochondroplasia and achondroplasia map to the same locus6,13. We therefore began a systematic screening of FGFR3 to detect mutations in patients with hypochondroplasia. We now report a single FGFR3 mutation found in 8 out of 14 unrelated patients with hypochondroplasia. This mutation causes a C to A transversion at nucleotide 1620, resulting in an Asn540Lys substitution in the proximal tyrosine kinase domain.

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Authors and Affiliations

  1. Center for Medical Genetics, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland, 21287, USA

    Gary A. Bellus, Iain McIntosh, E. Anne Smith & Clair A. Francomano

  2. Medical Genetics Branch, National Center for Human Genome Research, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Iain McIntosh & Clair A. Francomano

  3. Department of Pediatrics and the Brain and Development Research Center, University of North Carolina, Chapel Hill, North Carolina, 27599, USA

    Arthur S. Aylsworth

  4. Department of Clinical Genetics, Helsinki University Hospital, Helsinki, SF-00290, Finland

    Ilkka Kaitila

  5. Department of Research, Shriner's Hospital for Crippled Children, Portland, Oregon, 97201, USA

    William A. Horton

  6. Department of Pediatrics, University of Texas Medical School, Houston, Texas, 77225, USA

    Giselle A. Greenhaw & Jacqueline T. Hecht

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  1. Gary A. Bellus
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Bellus, G., McIntosh, I., Smith, E. et al. A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia. Nat Genet 10, 357–359 (1995). https://doi.org/10.1038/ng0795-357

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