Increased de novo Purine Synthesis in Cultured Skin Fibroblasts from Heterozygotes for the Lesch-Nyhan Syndrome

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Abstract
The metabolic consequence of hypoxanthine-guanine phosphoribosyltransferase deficiency, an accelerated rate of de novo purine synthesis, was utilized as a marker for the detection of heterozygosity for the Lesch-Nyhan syndrome in cultured human fibroblasts. This marker was very sensitive and allowed the detection of mutant cells in nonselected mixed mutant normal cell cultures even at a 1:10 ratio. Exposure of the mixed cultures to selection for the mutant cell with azaguanine increased the sensitivity of the test. Cultures from biopsies obtained from heterozygote females contained different proportions of the mutant cell (10-84%). Applicability to genetic counseling is discussed.