title: Pathophysiological Significance of Dermatan Sulfate Proteoglycans Revealed by Human Genetic Disorders.
abstract: The indispensable roles of dermatan sulfate-proteoglycans (DS-PGs) have been demonstrated in various biological events including construction of the extracellular matrix and cell signaling through interactions with collagen and transforming growth factor-β, respectively. Defects in the core proteins of DS-PGs such as decorin and biglycan cause congenital stromal dystrophy of the cornea, spondyloepimetaphyseal dysplasia, and Meester-Loeys syndrome. Furthermore, mutations in human genes encoding the glycosyltransferases, epimerases, and sulfotransferases responsible for the biosynthesis of DS chains cause connective tissue disorders including Ehlers-Danlos syndrome and spondyloepimetaphyseal dysplasia with joint laxity characterized by skin hyperextensibility, joint hypermobility, and tissue fragility, and by severe skeletal disorders such as kyphoscoliosis, short trunk, dislocation, and joint laxity. Glycobiological approaches revealed that mutations in DS-biosynthetic enzymes cause reductions in enzymatic activities and in the amount of synthesized DS and also disrupt the formation of collagen bundles. This review focused on the growing number of glycobiological studies on recently reported genetic diseases caused by defects in the biosynthesis of DS and DS-PGs.
authors.affiliation: Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan. mizumoto@meijo-u.ac.jp.
authors.forename: Shuji
authors.initials: S
authors.lastname: Mizumoto
authors.affiliation: Center for Medical Genetics, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. shuheiy@meijo-u.ac.jp.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kosho
authors.affiliation: Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan. ktomoki@shinshu-u.ac.jp.
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. mizumoto@meijo-u.ac.jp.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sugahara
keywords: Ehlers-Danlos syndrome; biglycan; carbohydrate sulfotransferase 14; chondroitin sulfate; decorin; dermatan 4-O-sulfotransferase; dermatan sulfate; dermatan sulfate epimerase; glycosaminoglycan; proteoglycan; spondyloepimetaphyseal dysplasia.