About 60% of cases of HCH are due to mutations in the intracellular FGFR3-tyrosine kinase domain, such as N540K, I538 V, though mutations may present in every domain of FGFR3.[21,40,41] In this research, by using NGS and Sanger sequencing, we identified a novel missense mutation (C1052T) resulting in S351F substitution in the extracellular domain Ig III in a very large Chinese family consisting of 53 affected individuals with classic HCH phenotypes. Here, FGFR3 is linked to hypochondroplasia.