{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T03:39:24Z","timestamp":1784259564530,"version":"3.55.0"},"reference-count":23,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2007,1,2]],"date-time":"2007-01-02T00:00:00Z","timestamp":1167696000000},"content-version":"vor","delay-in-days":2314,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Paediatrica"],"published-print":{"date-parts":[[2000,9]]},"abstract":"<jats:p>Hypochondroplasia is characterized by a disproportionate short stature with rhizomelic shortening of the limbs. Amino acid substitutions Asn540Lys, Asn540Thr and Ile538Val in the fibroblast growth factor receptor 3 (FGFR3) are considered to cause hypochondroplasia. In this study we examined the <jats:italic>FGFR3<\/jats:italic> gene for the previously described hypochondroplasia mutations and the phenotype of 23 probands with clinically and radiologically diagnosed hypochondroplasia. For the phenotype comparison, the patients were divided into two groups: Group 1: hypochondroplasia with Asn540Lys substitution; Group 2: hypochondroplasia with no mutations identified so far. A three\u2010generation family negative for the known hypochondroplasia mutations was examined with polymorphic markers flanking the <jats:italic>FGFRI, FGFR2<\/jats:italic> and <jats:italic>FGFR3<\/jats:italic> genes. Nine (39%) of 23 probands were found to be heterozygous for the Asn540Lys substitution. The individuals positive for the Asn540Lys substitution were significantly more disproportionate than the individuals without this mutation. In this respect, a genotype\u2013phenotype correlation was found in our patients. However, some individuals belonging to the group without mutations identified so far showed similarly abnormal proportions. Genotyping\/haplotyping in the three\u2010generation family with hypochondroplasia showed that <jats:italic>FGFR1, FGFR2<\/jats:italic> and <jats:italic>FGFR3<\/jats:italic> genes were not linked to the hypochondroplasia phenotype in this family, thus further confirming the genetic heterogeneity of hypochondroplasia.<\/jats:p><jats:p> <jats:italic>Conclusion<\/jats:italic>: Individuals with hypochondroplasia heterozygous for the Asn540Lys substitution are significantly more disproportionate than individuals without this mutation. Our study further confirms the clinical and genetic heterogeneity of hypochondroplasia.<\/jats:p>","DOI":"10.1111\/j.1651-2227.2000.tb03353.x","type":"journal-article","created":{"date-parts":[[2010,8,7]],"date-time":"2010-08-07T02:14:08Z","timestamp":1281147248000},"page":"1072-1076","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Asn540Lys mutation in fibroblast growth factor receptor 3 and phenotype in 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