Abnormal proteodermatan sulfate in three patients with Coffin-Lowry syndrome.
The properties of [35S]sulfate-labeled proteoglycans secreted by normal human skin fibroblasts were compared with those synthesized by fibroblasts from three patients with Coffin-Lowry syndrome. 60-80% of secreted radioactive macromolecules from normal fibroblasts were eluted from a Sepharose CL-4B column with a mean Kav-value of 0.56 (pool 2); 3-10% of the radioactivity appeared in the exclusion volume of the column (pool 1). In contrast, 17-60% of the proteoglycans from the patients were found in the void volume. The bulk of remaining material was eluted with a mean Kav-value of 0.47. Pool 2 glycan chains from two patients exhibited an increased hydrodynamic size. Pool 1 from normal cells contained predominantly a glucuronic acid-rich proteodermatan sulfate, iduronic acid amounting for approximately 20% of glucuronic acid. In the respective proteodermatan sulfate from the patients, the relative iduronic acid content was at least 33% of that of glucuronic acid. Pool 2 material of all cell lines was characterized predominantly as iduronic acid-rich proteodermatan sulfate. In the proteoglycans from two patients the content of chondroitin 4-sulfate-derived disaccharides was increased at the expense of 6-sulfated chondroitin disaccharides. Native proteoglycans from the patients were less efficiently endocytosed by fibroblasts than their normal counterparts. Coffin-Lowry fibroblasts had a normal capability to synthesize glycosaminoglycan chains on an artificial acceptor, p-nitrophenyl-beta-D-xyloside. They were also normal in 3'-phosphoadenylylsulfate: chondroitin 4- and 6-sulfotransferase activities.
D000015:Abnormalities, Multiple / Q000378:metabolism; D000328:Adult; D001842:Bone and Bones / Q000378:metabolism; D002478:Cells, Cultured; D002675:Child, Preschool; D002807:Chondroitin / Q000031:analogs & derivatives*; D003871:Dermatan Sulfate / Q000031:analogs & derivatives* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D005965:Glucuronates / Q000378:metabolism; D020723:Glucuronic Acid; D006801:Humans; D007067:Iduronic Acid / Q000378:metabolism; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011509:Proteoglycans / Q000378:metabolism*; D012737:Sex Factors; D012867:Skin / Q000166:cytology; D012871:Skin Diseases / Q000378:metabolism; D013577:Syndrome
D005965:Glucuronates; D011509:Proteoglycans; C028774:proteodermatan sulfate; D003871:Dermatan Sulfate; D007067:Iduronic Acid; D020723:Glucuronic Acid; D002807:Chondroitin