Genetic heterogeneity of hypoxanthine‐phosphoribosyl transferase in human fibroblasts of 3 families*

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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‐Nyhan syndrome, from two families with variant H‐PRT mutations and three cell strains from patients with the Lesch‐Nyhan syndrome were investigated. Cells from patients with the Lesch‐Nyhan 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.