A new method for the detection of Lesch-Nyhan heterozygotes by peripheral blood T cell culture using T cell growth factor.
Thioguanine-resistant T lymphoblast populations were selectively amplified using T cell growth factor in the cultures of peripheral blood T cells from four Lesch-Nyhan heterozygotes. Although Lesch-Nyhan T lymphoblasts were all thioguanine-resistant, none of the cultures from 13 control subjects yielded the growth of such defective cell populations. These data provide direct evidence for the existence of a small percentage (5%-40%) of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficient T cells in the heterozygotes, but not in normal individuals. Conversely, culture of the T lymphoblasts with azaserine plus hypoxanthine permitted the growth of the other part of the cell population that was enzyme positive. The low percentages of HGPRT-negative cells among T cells in heterozygotes suggest that the presence of this enzyme is beneficial for differentiation of lymphocytes of T cell linkage. Considering the ease and the reliability, culture of the peripheral T cells with thioguanine and T cell growth factor is very likely of practical use for detecting Lesch-Nyhan syndrome carriers among predisposed females.
D000293:Adolescent; D002455:Cell Division; D002478:Cells, Cultured; D002648:Child; D003470:Culture Media; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods*; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D007926:Lesch-Nyhan Syndrome / Q000097:blood* / Q000235:genetics; D008213:Lymphocyte Activation; D008297:Male; D013601:T-Lymphocytes / Q000166:cytology* / Q000473:pathology; D013866:Thioguanine / Q000494:pharmacology
D003470:Culture Media; D007376:Interleukin-2; D013866:Thioguanine