Increased de novo purine synthesis in cultured skin fibroblasts from heterozygotes for the Lesch-Nyhan syndrome. A sensitive marker for carrier detection.

The metabolic consequence of hypoxanthine-guanine phosphoribosyltransferase deficiency, the accelerated rate of purine synthesis de novo, was utilized as a marker for the detection in cultured fibroblasts of heterozygosity for the Lesch-Nyhan syndrome. This marker was found to be very sensitive allowing the detection of mutant cells in nonselected mixed mutant: normal cell cultures even at low proportion of 1 to 10. Exposure of the mixed cultures to selection for the mutant cell with azaguanine increased the sensitivity of the test. Cultures from different biopsies, obtained from heterozygote females, were found to contain different proportions of the mutant cell, ranging from 10 to 84%.