A GENETIC-DEFECT IN THE BIOSYNTHESIS OF DERMATAN SULFATE PROTEOGLYCAN - GALACTOSYLTRANSFERASE-I DEFICIENCY IN FIBROBLASTS FROM A PATIENT WITH A PROGEROID SYNDROME

A small proteoglycan that contains only a single dermatan sulfate chain is the main proteoglycan synthesized by skin fibroblasts. Fibroblasts from a patient with progeroidal appearance and symptoms of the Ehlers-Danlos syndrome have a reduced ability of converting the core protein of this proteoglycan into a mature glycosaminoglycan chain-bearing species. This abnormality is the consequence of a deficiency in galactosyltransferase I (xylosylprotein 4-β-galactosyltransferase; EC 2.4.1.133), which catalyzes the second glycosyl transfer reaction in the assembly of the dermatan sulfate chain. The glycosaminoglycan-free core protein secreted by the patient's fibroblasts bears an unsubstituted xylose residue. The mutant enzyme is abnormally thermolabile. Preincubation of fibroblasts at 41°C leads to a further reduction in the production of mature proteoglycan and affects the capacity for glycosaminoglycan synthesis on p-nitrophenyl β-D-xyloside more strongly in the mutant than in control cells.