Hypochondroplasia, achondroplasia, and thanatophoric dysplasia caused by mutations of the fibroblast-growth-factor-receptor-3-gene (FGFR3)

Background: In 1994, achondroplasia, the most common form of chondrodysplasia, was shown to be caused essentially by one specific mutation in the fibroblast-growth-factor-receptor-3-gene (FGFR3). Subsequently characteristic FGFR3 mutations have been identified in other members of this chondrodysplasia family. These are the thanatophoric dysplasia type I and II and the hypochondroplasia,the mildest form of this clinical spectrum. Methods: Here we report the molecular analysis of the FGFR3 gene in 169 patients (83 achondroplasia, 77 hypochondroplasia, 8 thanatophoric dysplasia type I, 1 thanatophoric dysplasia type II). Results: We show that about 93% of achondroplasia were caused by the same mutation in the transmembrane domain of FGFR3 while characteristic FGFR3 mutations could be ascertained in only 65% of hypochondroplasia cases. Conclusions: This supports the view that HCH is a heterogeneous condition with a difficult clinical and radiological diagnosis. The rate of identified mutations in thanatophoric dysplasia type I and II was 100%. Molecular analysis of FGFR3 is an important diagnostic tool. For a more detailed understanding of biological consequences of FGFR3 gene mutations and their pathological changes additional studies are necessary.