RESUMO
BACKGROUND: Achondroplasia, the most common type of genetic dwarfism characterised by disproportionate short stature and other skeletal anomalies, results from a defect in the maturation of the chondrocytes in the growth plate cartilage. Hypochondroplasia, considered allelic to achondroplasia is clinically and genetically heterogeneous. Recent studies have mapped the gene on chromosome 4p16.3, and frequent mutations in the fibroblast growth factor 3 (FGFR3) have been described in these diseases in other populations. PATIENTS AND METHODS: Analysis of the FGFR3 gene mutations Gly380Arg and Asn540Lys in 20 Spanish patients (10 achondroplasic, 6 hypochondroplasic and 4 with skeletal dysplasias with some phenotypic and radiological characteristics of hypochondroplasia) by PCR and restriction analysis. RESULTS: All the achondroplasic patients have shown the same mutation (Gly380Arg) in the transmembrane domain of the receptor. Five hypochondroplasic patients presented the mutation Asn540Lys in the proximal thirosine kinase domain. CONCLUSIONS: Achondroplasia in this sample from Spanish patients is also homogeneous in its molecular basis. Genetic heterogeneity has been found in hypochondroplasia corresponding with the phenotypic diversity in this disease. Molecular analysis of FGFR3 may be an additional diagnostic tool and facilitates genetic counselling in these chondrodysplasias.