heparitin-sulfate and Dwarfism

Perlecan, a basement membrane-type heparan sulfate proteoglycan, is an important molecule in the functional diversity of organisms because of the diversity of its glycan chains and the multifunctionality of its core proteins. Human diseases associated with perlecan have been identified using gene-deficient mice. Two human diseases related to perlecan have been reported. One is Silverman-Handmaker type dyssegmental dysplasia, resulting from the complete loss of function of the HSPG2 gene that encodes perlecan core protein, which is mapped to chromosome 1p36. The other is Schwartz-Jampel syndrome resulting from the partial loss of function of the

Topics: Animals; Dwarfism; Extracellular Matrix Proteins; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Mice; Osteochondrodysplasias

Glycosaminoglycans, including chondroitin, dermatan, and heparan sulfate, have various roles in a wide range of biological events such as cell signaling, cell proliferation, tissue morphogenesis, and interactions with various growth factors. Their polysaccharides covalently attach to the serine residues on specific core proteins through the common linker region tetrasaccharide, -xylose-galactose-galactose-glucuronic acid, which is produced through the stepwise addition of respective monosaccharides by four distinct glycosyltransferases. Mutations in the human genes encoding the glycosyltransferases responsible for the biosynthesis of the linker region tetrasaccharide cause a number of genetic disorders, called glycosaminoglycan linkeropathies, including Desbuquois dysplasia type 2, spondyloepimetaphyseal dysplasia, Ehlers-Danlos syndrome, and Larsen syndrome. This review focused on recent studies on genetic diseases caused by defects in the biosynthesis of the common linker region tetrasaccharide.

Topics: Cell Proliferation; Chondroitin; Craniofacial Abnormalities; Dermatan Sulfate; Dwarfism; Ehlers-Danlos Syndrome; Glycosyltransferases; Heparitin Sulfate; Humans; Joint Instability; Morphogenesis; Mutation; Ossification, Heterotopic; Osteochondrodysplasias; Polydactyly