RESUMO
Background: Achondroplasia and hypochondroplasia are skeletal dysplasias of autosomal dominant inheritance that represent different degrees of severity of the same pathological entity. Both dysplasias are caused by mutations in the Fibroblast Growth Factor Receptor 3 (FGFR3) gene. In achondroplasia more than 95% of the cases studied to date carry the same mutation (G380R). Hypochondroplasia represents a greater clinical and genetic heterogeneity, possibly being confused with "idiopathic short stature". The N540K mutation has been detected in 50-70% of cases of hypochondroplasia and mutations at the 650 locus in approximately 2.8%. Aim: To assess the frequency of N540K and G380R mutations, and changes at the 650 locus in Chilean patients with idiopathic disproportionate short stature, hypochondroplasia and achondroplasia. Patients and Methods: We studied 21 patients referred for idiopathic short stature, 5 with clinically suspected hypochondroplasia and 4 with achondroplasia. The G1138A, G1138C (G380R), and C1620, C1620A (N540K) mutations and the nucleotide changes at the 650 locus were studied using PCR and restriction analysis of genomic DNA. Results: Three out of five hypochondroplasia patients were heterozygous for the N540K mutation. All of the 4 patients with achondroplasia presented the G1138A mutation. None of these mutations were found in patients with idiopathic short stature. Conclusion: Chilean patients with hypochondroplasia and achondroplasia have the same mutations described in other ethnic groups. The identification of mutations in 3 out of 5 patients with hypochondroplasia shows that this analysis is a useful tool for its diagnostic confirmation. In short stature the molecular study should only be indicated in those cases presenting other clinical and/or radiological features of hypochondroplasia (Rev Méd Chile 2003; 131: 1405-10).
