Lesch–Nyhan disease is an X-linked recessive disorder in which the specific biochemical defect is absence of hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) activity. Detection of the phenotypically normal heterozygote has relied upon identification of two populations of cells, HGPRTase positive and HGPRTase negative, in cultures of skin fibroblasts. We analyzed hair roots from seven heterozygotes for HGPRTase activity. Six subjects could be distinguished from normal persons by this technic, demonstrating that mosaicism can be detected by hair-root analysis. The seventh, although clearly a heterozygote by skin fibroblast studies, had hair-root findings similar to those of normal persons. Our results suggest that hair-root analysis is a simple and rapid method for identifying the heterozygote for Lesch–Nyhan disease. However, hair-root analysis and tissue-culture technics should be considered complementary approaches, both of which may be essential in selected cases for excluding the possibility of mosaicism.
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