We examined the G380R mutation (G > A and G > C transition) and the mutation G375C (G > T transition at codon 375) in 31 sporadic patients and in one family diagnosed clinically to have achondroplasia.
Here we show that a glycine-to-cysteine substitution at position 375 (Gly375Cys) in human FGFR3 causes ligand-independent dimerization and phosphorylation of FGFR3 and that the equivalent substitution at position 369 (Gly369Cys) in mouse FGFR3 causes dwarfism with features mimicking human achondroplasia.
Chimeras of the native form or achondroplasia mutant (G375C) of human fibroblast growth factor receptor 3 induce ligand-dependent differentiation of PC12 cells.
We report on a newborn with achondroplasia who does not carry a G380R mutation but has a mutation causing substitution of a nearby glycine with a cysteine (G375C).