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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Orphanet Journal of Rare Diseases Open Access 18 April 2023
A novel S269C mutation in fibroblast growth factor receptor 3 in a Japanese child with hypochondroplasia
Human Genome Variation Open Access 12 April 2018
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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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