title: Genetic heterogeneity of hypoxanthine-phosphoribosyl transferase in human fibroblasts of 3 families.
abstract: Incorporation of hypoxanthine, resistance to 8-azaguanine and activation by lyophilisation have been studied in cultured human fibroblasts. Cells from one family where there was a boy with Lesch-Nyham syndrome, from two families with variant H-PRT mutations and three cell strains from patients with the Lesch-Nyham syndrome were investigated. Cells from patients with the Lesch-Nyham syndrome showed almost no hypoxanthine incorporation and resistance to concentrations of 8-azaguanine up to 10(-3) M, whereas cells of patients with partial H-PRT deficiency demonstrated variant patterns of hypoxanthine uptake and partial resistance to 8-azaguanine. Lyophilisation of fibroblast sediment from patients with the Lesch-Nyhan syndrome and patients with variant H-PRT mutations showed activation of the deficient or partially deficient H-PRT enzyme. No such activation was observed in healthy controls. Activation of lyophilised fibroblast extract from patients and controls was not obtained. These results suggest that H-PRT could be associated with the cell membranes.
mesh_terms: D001375:Azaguanine / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005612:Freeze Drying; D006358:Hot Temperature; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency / Q000378:metabolism*; D007042:Hypoxanthines / Q000378:metabolism; D007926:Lesch-Nyhan Syndrome / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation
chemical_list: D007042:Hypoxanthines; D007041:Hypoxanthine Phosphoribosyltransferase; D001375:Azaguanine