A compound heterozygote harboring novel and recurrent DTDST mutations with intermediate phenotype between atelosteogenesis type II and diastrophic dysplasia.

Diastrophic dysplasia sulfate transporter (DTDST) is a sulfate transporter required for the synthesis of sulfated proteoglycans in the cartilage. Over 30 mutations have been described in the DTDST gene, which result in a continuous clinical spectrum of recessively inherited chondrodysplasias, including, in order of increasing severity, a recessive form of multiple epiphyseal dysplasia (rMED), diastrophic dysplasia (DTD), atelosteogenesis type II (AO-II) and achondrogenesis 1B (ACG-1B). Correlation between disease severity and residual sulfate transport activity has been reported. Here we report a patient with DTDST mutations, whose manifestations fell in a range between AO-II and DTD. The patient was a compound heterozygote for the recurrent c.835C>T (p.R279W) and novel c.1987G>A (p.G663R) mutations. Immunocytochemical analysis in HEK293 cells showed that the p.G663R mutation was localized within the cytoplasm, and not to the cell membrane, suggesting p.G663R is a loss-of-function mutation. Our case supports the previously described correlation between the severity of the phenotype and the putative level of residual transport function.