A diastrophic dysplasia sulfate transporter (SLC26A2) mutant mouse: morphological and biochemical characterization of the resulting chondrodysplasia phenotype.
Using mesenchymal stem cells (MSCs) in an in vitro chondrogenesis assay, we found that knockdown of the diastrophic dysplasia (DTD) sulfate transporter (DTDST, also known as SLC26A2), which is required for normal cartilage development, blocked cell condensation and caused a significant reduction in fibronectin matrix.
Importantly, mutations in SLC26A2, A3, A4, and A5 have been associated with distinct human genetic recessive disorders (i.e. diastrophic dysplasia, congenital chloride diarrhea, Pendred syndrome and deafness, respectively), demonstrating their essential and non-redundant functions in many tissues.
Mutations in the sulfate transporter gene, SCL26A2, lead to cartilage proteoglycan undersulfation resulting in chondrodysplasia in humans; the phenotype is mirrored in the diastrophic dysplasia (dtd) mouse.
Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias.
The fetus affected by McAlister dysplasia we have studied is a compound heterozygote for mutations leading to R279W and N425D substitutions in the diastrophic dysplasiasulfate transporter.
Five fetuses in families with a previous history of DTD were studied by typing them and their relevant family members for DNA markers closely linked to the DTD gene.
Diastrophic dysplasia and atelosteogenesis type II as expression of compound heterozygosis: first report of a Mexican patient and genotype-phenotype correlation.
A compound heterozygote harboring novel and recurrent DTDST mutations with intermediate phenotype between atelosteogenesis type II and diastrophic dysplasia.
A homozygous R279W mutation was recently found in the diastrophic dysplasiasulfate transporter gene, DTDST, in a patient with MED who had a club foot and double-layered patella.
Using these methods, we report striking linkage disequilibrium for diastrophic dysplasia (DTD) in Finland indicating that the DTD gene should lie within 0.06 centimorgans (or about 60 kilobases) of the CSF1R gene.