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.