title: Mutations in Biosynthetic Enzymes for the Protein Linker Region of Chondroitin/Dermatan/Heparan Sulfate Cause Skeletal and Skin Dysplasias.
abstract: 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.
authors.affiliation: Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Mizumoto
authors.affiliation: Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan ; Laboratory of Proteoglycan Signaling and Therapeutics, Graduate School of Life Science, Hokkaido University, Sapporo 001-0021, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sugahara
mesh_terms: D049109:Cell Proliferation / Q000235:genetics; D002807:Chondroitin / Q000378:metabolism; D019465:Craniofacial Abnormalities / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D003871:Dermatan Sulfate / Q000378:metabolism; D004392:Dwarfism / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D004535:Ehlers-Danlos Syndrome / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D016695:Glycosyltransferases / Q000235:genetics*; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D007593:Joint Instability / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation; D009999:Ossification, Heterotopic / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D010009:Osteochondrodysplasias / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D017689:Polydactyly / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism
chemical_list: D002807:Chondroitin; D003871:Dermatan Sulfate; D016695:Glycosyltransferases; D006497:Heparan Sulfate