Molecular genetics of the human chondrodysplasias-1995.

A number of gene loci have recently been shown to harbor mutations that cause human chondrodysplasias. They encode proteins that occupy cartilage matrix, such as types II, IX, X and XI collagens and COMP, that transduce signals in the growth plate, i.e., FGFR3 and PTHrP receptor, that influence the transport and metabolism of sulfate ions in relevant cells, e.g., DTDST and arylsulfatase E, and that regulate transcription of other genes, such as SOX9. Mutations at two loci, COL2A1 and FGFR3, account for most patients with chondrodysplasias--those with spondyloepiphyseal dysplasia and the achondroplasia classes of disorders, respectively. Mutations in the former tend to be dispersed throughout the gene and in other functionally related genes, whereas mutations in the latter are restricted to a few codons that seem to be very mutable.