Mutations in Biosynthetic Enzymes for the Protein Linker Region of Chondroitin/Dermatan/Heparan Sulfate Cause Skeletal and Skin Dysplasias

• Published in: BioMed research international 2015-01, Vol.2015 (2015), p.1-7
• Main Authors: Mizumoto, Shuji, Sugahara, Kazuyuki, Yamada, Shuhei
• Format: Article
• Language: English
• Subjects: Acids; Biosynthesis; Cell growth; Cell Proliferation - genetics; Chondroitin - metabolism; Craniofacial Abnormalities - enzymology; Craniofacial Abnormalities - genetics; Craniofacial Abnormalities - metabolism; Dermatan Sulfate - metabolism; Development and progression; Dwarfism - enzymology; Dwarfism - genetics; Dwarfism - metabolism; Dysplasia; Ehlers-Danlos Syndrome - enzymology; Ehlers-Danlos Syndrome - genetics; Ehlers-Danlos Syndrome - metabolism; Enzymes; Fibroblasts; Glycosaminoglycans; Glycosyltransferases - genetics; Heparan sulfate; Heparitin Sulfate - metabolism; Humans; Joint Instability - enzymology; Joint Instability - genetics; Joint Instability - metabolism; Morphogenesis - genetics; Mutation; Ossification, Heterotopic - enzymology; Ossification, Heterotopic - genetics; Ossification, Heterotopic - metabolism; Osteochondrodysplasias - enzymology; Osteochondrodysplasias - genetics; Osteochondrodysplasias - metabolism; Physiological aspects; Polydactyly - enzymology; Polydactyly - genetics; Polydactyly - metabolism; Proteins; Review
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2015/861752

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.