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.