title: Defective glycosaminoglycan substitution of decorin in a patient with progeroid syndrome is a direct consequence of two point mutations in the galactosyltransferase I (beta4GalT-7) gene.
abstract: The small dermatan sulfate proteoglycan decorin is involved in the regulation of collagen fibrillogenesis, cell adhesion and migration, and growth factor signaling. In a progeroid patient carrying two point mutations in beta4 galactosyltransferase I (beta4GalT-7) only 50% of the decorin core protein molecules are substituted with glycosaminoglycan chains. We expressed decorin, as well as wild-type and mutant alleles of beta4GalT-7 in galactosyltransferase-deficient CHO618 cells. Decorin was less efficiently substituted with glycosaminoglycan chains upon expression of beta4GalT-7(186D) compared to beta4GalT-7-expressing cells. Decorin from beta4GalT-7-expressing cells displayed increased molecular heterogeneity. Decorin glycosaminoglycan chains were completely susceptible to chondroitinase ABC treatment. Cells expressing beta4GalT-7(206P) did not synthesize the proteoglycanform of decorin. Thus, the beta4GalT-7 mutations directly affect the molecular phenotype of decorin observed in a patient with the progeroid form of Ehlers-Danlos syndrome, which may be a major mechanistic cause for the skin and wound healing defects observed in this patient.
authors.affiliation: Department of Obstetrics and Gynecology, Münster University Hospital, Domagkstr-11, D-48149 Münster, Germany. mgotte@uni-muenster.de
authors.forename: Martin
authors.initials: M
authors.lastname: Götte
authors.forename: Hans
authors.initials: H
authors.lastname: Kresse
mesh_terms: D000818:Animals; D016466:CHO Cells; D003057:Cockayne Syndrome / Q000235:genetics*; D006224:Cricetinae; D058575:Decorin; D004535:Ehlers-Danlos Syndrome / Q000235:genetics*; D016326:Extracellular Matrix Proteins; D005700:Galactosyltransferases / Q000172:deficiency* / Q000235:genetics*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D017354:Point Mutation; D011509:Proteoglycans / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D011509:Proteoglycans; D005700:Galactosyltransferases; C063053:xylosylprotein 4-beta-galactosyltransferase