title: Glycosaminoglycan-free small proteoglycan core protein is secreted by fibroblasts from a patient with a syndrome resembling progeroid.
abstract: A male patient, 4 years 9 mo old and having progeroidal appearance, exhibited delayed mental development and multiple abnormalities of connective tissues including growth failure, osteopenia of all and dysplasia of some bones, defective deciduous teeth, loose but elastic skin, delayed wound healing with formation of thin atrophic scars, scanty scalp hair, hypotonic muscles, and hypermobile joints. Skin fibroblasts of the patient converted only about half of the core protein of the small proteodermatan sulfate to a mature glycosaminoglycan chain-bearing proteoglycan. The remaining core protein, which contained complex-type asparagine-bound oligosaccharides, was secreted with almost normal kinetics. Xylosyltransferase activity and the synthesis of other proteoglycan types were normal. Normal induction of glycosaminoglycan synthesis occurred in the presence of 1 mM, but there was very little induction in the presence of 0.01 mM p-nitrophenyl-beta-xyloside. An antibody against an N-terminal pentadecapeptide of the core protein recognized the glycosaminoglycan-free core protein from the patient less well than the chain-bearing protein treated with chondroitin ABC lyase. Though these results do not define the basic defect unambiguously, they provide the first report of a disorder being due to an abnormality in small proteoglycan biosynthesis.
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000378:metabolism*; D053674:Aggrecans; D002675:Child, Preschool; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis* / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D037181:Lectins, C-Type; D008297:Male; D011371:Progeria / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000096:biosynthesis*; D013577:Syndrome
chemical_list: D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D037181:Lectins, C-Type; D011509:Proteoglycans