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

Shuji Mizumoto; Shuhei Yamada; Kazuyuki Sugahara

doi:10.1155/2015/861752

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

Biomed Res Int. 2015:2015:861752. doi: 10.1155/2015/861752. Epub 2015 Oct 25.

Authors

Shuji Mizumoto¹, Shuhei Yamada¹, Kazuyuki Sugahara²

Affiliations

¹ Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
² 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.

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.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Cell Proliferation / genetics
Chondroitin / metabolism
Craniofacial Abnormalities / enzymology
Craniofacial Abnormalities / genetics*
Craniofacial Abnormalities / metabolism
Dermatan Sulfate / metabolism
Dwarfism / enzymology
Dwarfism / genetics*
Dwarfism / metabolism
Ehlers-Danlos Syndrome / enzymology
Ehlers-Danlos Syndrome / genetics*
Ehlers-Danlos Syndrome / metabolism
Glycosyltransferases / genetics*
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
Polydactyly / enzymology
Polydactyly / genetics*
Polydactyly / metabolism

Substances

Dermatan Sulfate
Chondroitin
Heparitin Sulfate
Glycosyltransferases

Supplementary concepts

Desbuquois syndrome
Larsen Syndrome