Advertisement

Human Genetics

, Volume 31, Issue 2, pp 127–150 | Cite as

Hypoxanthine-guanine phosphoribosyl transferase deficiency

  • Chris H. M. M. de Bruyn
Review Articles

Summary

In man congenital lack of an enzyme of the purine salvage system, hypoxanthineguanine phosphoribosyl transferase (HG-PRT E.C. 2.4.2.8), is mostly accompanied by a picture known as the Lesch-Nyhan syndrome. The degree of deficiency may vary from zero to a few percent of normal activity but a correlation between the severity of HG-PRT deficiency and the clinical picture has not been observed, no more than a correlation between HG-PRT deficiency and neurological dysfunction. But individuals with undetectable HG-PRT activity but without the Lesch-Nyhan syndrome have been described. Patients with partial HG-PRT deficiency have clinically distinctive findings. Sometimes mild neurological abnormalities are observed. Because of marked overproduction of uric acid severe gouty arthritis and renal dysfunction are often encountered in both complete and partial deficiency.

There is considerable molecular heterogeneity in HG-PRT deficiency in man. Mutant enzymes may exhibit different kinetic and electrophoretic properties, indicating that there might be a mutation on the structural gene coding for HG-PRT.

Lack of HG-PRT disturbs purine interconversions profoundly. In addition to an important function of HG-PRT in the uptake of the purine bases hypoxanthine and guanine into the cell, the effective uptake of inosine, guanosine and adenosine also seems to be dependent on HG-PRT. Uptake of purine bases into intact red blood cells occurs according to a two component mechanism, one component probably involving a phosphoribosyl transferase system.

The inheritance of HG-PRT deficiency is X-linked recessive and it is transmitted by asymptomatic carrier females. Several methods have been introduced for carrier detection. As a consequence of X chromosome inactivation, in these females a mosaicism of HG-PRT positive and HG-PRT negative fibroblasts can be demonstrated after cloning or after selection of HG-PRT negative cells in a selective medium. A more rapid method involves direct measurements of HG-PRT activities in single hair roots from the scalp. Because hair roots develop more or less clonally, in heterozygote females HG-PRT positive and negative hair roots are encountered. HG-PRT deficiency can be detected antenatally by demonstrating the presence or absence of enzyme activity in ammiotic fluid derived fibroblasts qualitatively by autoradiography and quantitatively by ultramicrochemical measurements of enzyme activities in single or small numbers of cells.

In studies with isolated cells the metabolic defect can be corrected in several ways. Metabolic cooperation between HG-PRT positive and HG-PRT negative cells leads to apparently normal phenotype of all cells, provided there is cell to cell contact. There is evidence that a missing enzyme product or a derivative might be transferred from the normal to the mutant cells. Apparent correction of the enzyme defect is also observed when HG-PRT deficient lymphocytes are stimulated with phytohaemagglutinin.

The first data suggestive of genetic complementation between two human HG-PRT deficient cell strains by which hybrid cells can synthesize a functionally active HG-PRT, are consistent with the view that HG-PRT deficiency in man is due to a structural gene mutation. Recent results show that other interesting findings might come from experiments in which HG-PRT deficient cells are treated with exogenous genetic material (isolated DNA or metaphase chromosomes) to reactivate or induce HG-PRT activity.

Keywords

Hair Root Missing Enzyme Gouty Arthritis Purine Base Transferase Deficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adams, A., Anderson, J. M., Nicol, A. D., Harkness, A.: The development of hypoxanthine-guanine phosphoribosyl transferase in man. Biochem. J. 125, 36 (1971)Google Scholar
  2. Albertini, R. J., De Mars, R.: Mosaicism of peripheral blood lymphocyte populations in females heterozygous for the Lesch-Nyhan mutation. Biochem. Genet. 11, 397–411 (1974)PubMedGoogle Scholar
  3. Andrews, T. M., Tata, J. R.: Protein synthesis by membrane bound and free ribosomes of the developing rat cerebral cortex. Biochem. J. 124, 883–889 (1971)PubMedGoogle Scholar
  4. Arnold, W. J., Kelley, W. N.: Human hypoxanthine-guanine phosphoribosyl transferase: purification and subunit structure. J. biol. Chem. 246, 7398–7404 (1971)PubMedGoogle Scholar
  5. Arnold, W. J., Mead, J. C., Kelley, W. N.: Hypoxanthine-guanine phosphoribosyl transferase: characteristics of the mutant enzyme in erythrocytes from patients with the Lesch-Nyhan syndrome. J. clin. Invest. 51, 1805–1812 (1972)PubMedGoogle Scholar
  6. Ashkenazi, Y. E., Gartler, S. M.: A study of metabolic cooperation utilizing human mutant fibroblasts. Exp. Cell Res. 64, 9–16 (1971)PubMedGoogle Scholar
  7. Ayad, S. R., Fox, M.: DNA uptake by a mutant strain of lymphoma cells. Nature (Lond.) 220, 35–38 (1968)Google Scholar
  8. Bakay, B., Croce, C. M., Koprowsky, H., Nyhan, W. L.: Restauration of hypoxanthine phosphoribosyl transferase activity in mouse 1R cells after fusion with chick-embryo fibroblasts. Proc. nat. Acad. Sci. (Wash.) 70, 1998–2002 (1973)Google Scholar
  9. Bakay, B., Nyhan, W. L.: Electrophoretic properties of hypoxanthine-guanine phosphoribosyl transferase in subjects with Lesch-Nyhan syndrome. Biochem. Genet. 6, 139–146 (1972)PubMedGoogle Scholar
  10. Bakay, B., Nyhan, W. L., Croce, C. M., Koprowsky, H.: Reversion in expression of hypoxanthine-guanine phosphoribosyl transferase following cell hybridisation. J. Cell Sci. 17, 567–578 (1975)PubMedGoogle Scholar
  11. de Bruyn, C. H. M. M.: Aspects of purine metabolism in man. Thesis, Nijmegen 1974Google Scholar
  12. de Bruyn, C. H. M. M., Oei, T. L.: Lesch-Nyhan syndrome: incorporation of hypoxanthine in stimulated lymphocytes. Exp. Cell Res. 79, 450–452 (1973)PubMedGoogle Scholar
  13. de Bruyn, C. H. M. M., Oei, T. L.: Purine metabolism in intact erythrocytes from controls and HG-PRT deficient individuals. In: Purine metabolism in man (eds. O. Sperling, A. de Vries, J. B. Wyngaarden) pp. 223–227. New York: Plenum Press 1974aGoogle Scholar
  14. de Bruyn, C. H. M. M., Oei, T. L.: Purine phosphoribosyl transferase in human hairroots. Dermatologica 149, 101–109 (1974b)PubMedGoogle Scholar
  15. de Bruyn, C. H. M. M., Oei, T. L.: Incorporation of 3H-hypoxanthine in PHA stimulated HG-PRT deficient lymphocytes. In: Purine metabolism in man (eds. O. Sperling, A. de Vries, J. B. Wyngaarden), pp. 229–235. New York: Plenum Press 1974cGoogle Scholar
  16. de Bruyn, C. H. M. M., Oei, T. L., Geerdink, R. A., Lommen, E. J. P.: An atypical case of hypoxanthine-guanine phosphoribosyl transferase deficiency (Lesch-Nyhan syndrome): II. Genetic studies. Clin. Genet. 40, 353–359 (1973)Google Scholar
  17. de Bruyn, C. H. M. M., Oei, T. L., ter Haar, B. G. A.: Studies on hairroots for carrier detection in hypoxanthine-guanine phosphoribosyl transferase deficiency. Clin. Genet. 5, 449–456 (1974)PubMedGoogle Scholar
  18. Burkholder, G. D., Mukherjee, B. B.: Uptake of isolated metaphase chromosomes by mammalian cells in vitro. Exp. Cell Res. 61, 413–422 (1970)PubMedGoogle Scholar
  19. Champanier, J. P., Etienne, J. C., Gougeon, J., Pascalis, G.: Encephalopathy with self mutilation in a twin. Normal HG-PRT activity. Hyperuricosuria without major hyperuricemia. Rev. Neuro-Psychiat. Infantile 20, 777–784 (1972)Google Scholar
  20. Chorazy, M., Bendich, A., Borenfreund, E., Hutchison, D. J.: Studies on the isolation of metaphase chromosomes. J. Cell Biol. 19, 59–69 (1963a)CrossRefPubMedGoogle Scholar
  21. Chorazy, M., Bendich, A., Borenfreund, E., Ittensohn, O. L., Hutchison, D. J.: Uptake of mammalian chromosomes by mammalian cells. J. Cell Biol. 19, 71–77 (1963b)CrossRefPubMedGoogle Scholar
  22. Chow, D. C., Kawahara, F. S., Saunders, T., Sorensen, L. B.: A new assay method for hypoxanthine-guanine phosphoribosyl transferase. J. Lab. clin. Med. 76, 733–738 (1970)PubMedGoogle Scholar
  23. Cox, R. P., Krauss, M. R., Balis, M. E., Dancis, J.: Evidence for transfer of enzyme product as the basis of metabolic cooperation between tissue culture fibroblasts of Lesch-Nyhan disease and normal cells. Proc. nat. Acad. Sci. (Wash.) 67, 1573–1579 (1970)Google Scholar
  24. Cox, R. P., Krauss, M. R., Balis, M. E., Dancis, J.: Communication between normal and enzyme deficient cells in tissue culture. Exp. Cell Res. 74, 251–268 (1972)PubMedGoogle Scholar
  25. Croce, C. M., Bakay, B., Nyhan, W. L., Koprowsky, H.: Re-expression of the rat hypoxanthine phosphoribosyl transferase gene in rat-human hybrids. Proc. nat. Acad. Sci. (Wash.) 70, 2590–2594 (1973)Google Scholar
  26. Dancis, J., Berman, P. H., Jansen, V., Balis, M. E.: Absence of mosaicism in the lymphocyte in X-linked congenital hyperuricemia. Life Sci. 7, 587–591 (1968)CrossRefPubMedGoogle Scholar
  27. Dancis, J., Cox, R. P., Berman, P. H. Jansen, V., Balis, M. E.: Cell population density and phenotypic expression of tissue culture fibroblasts from heterozygotes of Lesch-Nyhan's disease (Inosinate pyrophosphorylase deficiency). Biochem. Genet. 3, 609–615 (1969)PubMedGoogle Scholar
  28. Dancis, J., Yip, L. C., Cox, R. P., Piomelli, S., Balis, M. E.: Disparate enzyme activity erythrocytes and leukocytes; a variant of hypoxanthine phosphoribosyl transferase deficiency with an unstable enzyme. J. clin. Invest. 52, 2068–2074 (1973)PubMedGoogle Scholar
  29. Davidson, A. N., Dobbing, J.: Myelination as a vulnerable period in brain development. Brit. med. Bull. 22, 40–44 (1966)PubMedGoogle Scholar
  30. Davidson, R. L., Ephrussi, B., Yamamoto, K.: Regulation of pigment synthesis in mammalian cells, as studied by somatic hybridization. Proc. nat. Acad. Sci. (Wash.) 56, 1437–1440 (1966)Google Scholar
  31. De Mars, R., Sarto, G., Felix, J. S., Benke, P.: Lesch-Nyhan mutation: prenatal detection with amniotic fluid cells. Science 161, 1303–1305 (1969)Google Scholar
  32. DiChiara, C., Camba, R., Spano, P. F.: Evidence for inhibition by brain serotonin of mouse killing behaviour in rats. Nature (Lond.) 233, 272–273 (1971)Google Scholar
  33. Dobbing, J., Sands, J.: Vulnerability of developing brain (The effect of nutritional growth retardation on the timing of the brain growth-spurt). Biol. Neonate 19, 363–378 (1971)PubMedGoogle Scholar
  34. Dwosh, I. L., Moore, M., Fox, I. H.: Hypoxanthine-guanine phosphoribosyl transferase deficiency: phenotypic and genetic heterogeneity. J. Rheumatol. 1, 441–452 (1974)Google Scholar
  35. Emmerson, B. T., Thompson, C. J., Wallace, D. C.: Partial deficiency of hypoxanthine-guanine phosphoribosyl transferase: intermediate enzyme deficiency in heterozygote red cells. Ann. intern. Med. 76, 285–287 (1972)PubMedGoogle Scholar
  36. Emmerson, B. T., Wijngaarden, J. B.: Purine metabolism in heterozygous carriers of hypoxanthine-guanine phosphoribosyl transferase deficiency. Science 166, 1533–1535 (1969)Google Scholar
  37. Felix, J. S., De Mars, R.: Detection of females heterozygous for the Lesch-Nyhan mutation by 8-azaguanine-resistant growth of cultured fibroblasts. J. Lab. clin. Med. 77, 596–604 (1971)PubMedGoogle Scholar
  38. Francke, U., Bakay, B., Nyhan, W. L.: Detection of heterozygous carriers of the Lesch-Nyhan syndrome by electrophoresis of hairroot lysates. J. Pediat. 82, 472–478 (1973)PubMedGoogle Scholar
  39. Fratantoni, J. C., Hall, C. W., Neufeld, E. F.: Hurler and Hunter syndromes: mutual correction of the defect in cultured fibroblasts. Science 162, 570–572 (1968)PubMedGoogle Scholar
  40. Friedmann, T., Seegmiller, J. E., Subak-Sharpe, J. H.: Metabolic cooperation between genetically marked human fibroblasts in tissue culture. Nature (Lond.) 220, 272–274 (1968)Google Scholar
  41. Fujimoto, W. Y., Seegmiller, J. E., Uhlendorf, B. W., Jacobson, C. B.: Biochemical diagnosis of an X-linked disease in utero. Lancet 1968 II, 511–512Google Scholar
  42. Gartler, S. M., Gandini, E., Angioni, G., Argiolas, N.: Glucose-6-phosphate dehydrogenase mosaicism: utilization as a tracer in the study of a development of hairroot cells. Ann. hum. Genet. 33, 171–176 (1969)PubMedGoogle Scholar
  43. Gartler, S. M., Scott, R. C., Goldstein, J. L., Campbell, B., Sparkes, R.: Lesch-Nyhan syndrome: rapid detection of heterozygotes. Science 172, 572–574 (1971)PubMedGoogle Scholar
  44. Geerdink, R. A., de Vries, W. H. M., Willemse, J., Oei, T. L., de Bruyn, C. H. M. M.: An atypical case of hypoxanthine-guanine phosphoribosyl transferase deficiency (Lesch-Nyhan syndrome): I. Clinical studies. Clin. Genet. 40, 348–352 (1973)Google Scholar
  45. Ghadimi, H., Bhalla, C. K., Kirchenbaum, D. M.: The significance of the deficiency state in Lesch-Nyhan disease. Acta paediat. scand. 59, 233–240 (1970)PubMedGoogle Scholar
  46. Gilula, N. B., Reeves, O. R., Steinbach, A.: Metabolic coupling, ionic coupling and cell contacts. Nature (Lond.) 235, 262–265 (1972)Google Scholar
  47. Greene, M. L.: Clinical features of patients with the partial deficiency of the X-linked uricaciduria enzyme. Arch. intern. Med. 130, 193–198 (1972)CrossRefPubMedGoogle Scholar
  48. Greene, M. L., Boyle, J. A., Seegmiller, J. E.: Substrate stabilisation: genetically controled reciprocal relationship of two human enzymes. Science 167, 887–889 (1970a)PubMedGoogle Scholar
  49. Greene, M. L., Nyhan, W. L., Seegmiller, J. E.: Hypoxanthine-guanine phosphoribosyl transferase deficiency and Xg bloodgroup. Amer. J. hum. Genet. 22, 50–54 (1970b)PubMedGoogle Scholar
  50. Gutensohn, W., Guroff, G.: Hypoxanthine-guanine phosphoribosyl transferase from rat brain (purification, kinetic properties, development and distribution). J. Neurochem. 19, 2139–2150 (1972)PubMedGoogle Scholar
  51. Hagemeijer, A. M., Dodinval, P., Andrien, J. M.: Syndrome de Lesch-Nyhan: détection des hétérozygotes. Hum. Genet. 15, 126–135 (1972)Google Scholar
  52. Harris, H., Miller, O. J., Klein, G., Worst, P., Tachibana, T.: Suppression of malignancy by cell fusion. Nature (Lond.) 223, 363–368 (1969)Google Scholar
  53. Henderson, J. F.: Inheritance of hypoxanthine-guanine phosphoribosyl transferase deficiency and detection of heterozygotes. Fed. Proc. 27, 1085–1086 (1968)PubMedGoogle Scholar
  54. Henderson, J. F., Fraser, J. H., McCoy, E. E.: Methods for the study of purine metabolism in human cells in vitro. Clin. Biochem. 7, 339–358 (1974)PubMedGoogle Scholar
  55. Henderson, J. F., Kelley, W. N., Rosenbloom, F. M., Seegmiller, J. E.: Inheritance of purine phosphoribosyl transferases in man. Amer. J. hum. Genet. 21, 61–70 (1969)PubMedGoogle Scholar
  56. Henderson, J. F., Khoo, M. K. Y.: Synthesis of 5-phosphoribosyl-1-pyrophosphate from glucose in Ehrlich ascites tumor cells in vitro. J. biol. Chem. 240, 2349–2359 (1965)PubMedGoogle Scholar
  57. Hill, M., Hillova, J.: Recombinational events between exogenous mouse DNA and newly synthesized RNA strands of chicken cells in culture. Nature (Lond.) New Biol. 231, 261–265 (1971)Google Scholar
  58. Hoefnagel, D.: Summary, proceedings seminar on the Lesch-Nyhan syndrome. Fed. Proc. 27, 1042–1046 (1968)PubMedGoogle Scholar
  59. Hösli, P.: Tissue cultivation on plastic films. Tecnomara A.G., Rieterstrasse 59, Postfach CH 8059, Zürich, Switzerland (1972)Google Scholar
  60. Hösli, P., de Bruyn, C. H. M. M., Oei, T. L.: Development of a micro HG-PRT activity assay: preliminary complementation studies with Lesch-Nyhan cell strains. In: Purine metabolism in man (eds. O. Sperling, A. de Vries, J. B. Wyngaarden), pp. 811–815 New York: Plenum Press 1974Google Scholar
  61. Howard, W. J., Kerson, L. A., Appel, S. H.: Synthesis de novo of purines in slices of rat brain and liver. J. Neurochem. 17, 121–123 (1970)PubMedGoogle Scholar
  62. Itiaba, K., Banfalvi, M., Crawhall, J. C.: Metabolism of purines in cultures normal and HG-PRT deficient human fibroblasts. Biochem. Genet. 8, 149–156 (1973)PubMedGoogle Scholar
  63. Kaufman, J. M., O'Brien, W. M.: Hyperuricemia in mongolism. New Engl. J. Med. 276, 953–956 (1967)PubMedGoogle Scholar
  64. Kelley, W. N.: Hypoxanthine-guanine phosphoribosyl transferase deficiency in the Lesch-Nyhan syndrome and gout. Fed. Proc. 27, 1047–1052 (1968)PubMedGoogle Scholar
  65. Kelley, W. N., Greene, M. L., Rosenbloom, F. M., Henderson, J. F., Seegmiller, J. E.: Hypoxanthine-guanine phosphoribosyl transferase in gout. Ann. intern. Med. 70, 155–206 (1969)PubMedGoogle Scholar
  66. Kelley, W. N., Meade, J. E.: Studies on hypoxanthine-guanine phosphoribosyl transferase in fibroblasts from patients with the Lesch-Nyhan syndrome. J. biol. Chem. 246, 2953–2958 (1971)PubMedGoogle Scholar
  67. Kelley, W. N., Rosenbloom, F. M., Henderson, J. F., Seegmiller, J. E.: A specific enzyme defect in gout associated with overproduction of uric acid. Proc. nat. Acad. Sci. (Wash.) 57, 1735–1739 (1967)Google Scholar
  68. Kelley, W. N., Rosenbloom, F. M., Seegmiller, J. E., Howell, R. R.: Excessive production of uric acid in type I glycogen storage disease. J. Pediat. 72, 488–496 (1968)PubMedGoogle Scholar
  69. Kelley, W. N., Wyngaarden, J. B.: The Lesch-Nyhan syndrome. In: The metabolic basis of inherited disease (eds. J. B. Stanbury, J. B. Wyngaarden, D. S. Frederickson), 3rd ed., pp. 969–991. New York: McGraw Hill 1972Google Scholar
  70. Kogut, M. D., Donnel, G. N., Nyhan, W. L., Sweetman, L.: Disorder of purine metabolism due to partial deficiency of hypoxanthine-guanine phosphoribosyl transferase. Amer. J. Med. 48, 148–161 (1970)CrossRefPubMedGoogle Scholar
  71. Ledoux, L.: Uptake of DNA by living cells. Progr. Nucl. Acid Res. 4, 231–267 (1965)Google Scholar
  72. Lesch, M., Nyhan, W. L.: A familial disorder of uric acid metabolism and central nervous system function. Amer. J. Med. 36, 561–570 (1964)CrossRefPubMedGoogle Scholar
  73. Littlefield, J. W.: Three degrees of guanylic acid-inosinic acid pyrophosphorylase deficiency in mouse fibroblasts. Nature (Lond.) 203, 1142–1144 (1964a)Google Scholar
  74. Littlefield, J. W.: Selection of hybrids from matings of fibroblasts in vitro and their presumed recombinants. Science 145, 709–710 (1964b)PubMedGoogle Scholar
  75. Lyon, M. F.: Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature (Lond.) 190, 372–373 (1961)Google Scholar
  76. McBride, O. W., Ozer, H. L.: Transfer of genetic information by purified metaphase chromosomes. Proc. nat. Acad. Sci. (Wash.) 70, 1258–1262 (1973)Google Scholar
  77. McDonald, J. A., Kelley, W. N.: Lesch-Nyhan syndrome: altered kinetic properties of the mutant enzyme. Science 171, 689–691 (1971)PubMedGoogle Scholar
  78. McDonald, J. A., Kelley, W. N.: Lesch-Nyhan syndrome: absence of mutant enzyme in erythrocytes of a heterozygote for both normal and mutant hypoxanthine-guanine phosphoribosyl transferase. Biochem. Genet. 6, 21–26 (1972)PubMedGoogle Scholar
  79. McKeran, H. A., Andrews, T. M., Watts, R. W. E., Arlett, C. F.: Observations on the growth in vitro of myeloid progenitor cells and fibroblasts from hemizygotes and heterozygotes for “complete” and “partial” hypoxanthine-guanine phosphoribosyl transferase (HG-PRT) deficiency, and their relevance to the pathogenesis of brain damage in the Lesch-Nyhan syndrome. J. neurol. Sci. 22, 188–195 (1974)CrossRefGoogle Scholar
  80. Meera Khan, P., Westerveld, A., Grezschik, K. H., Deys, B. F., Garson, O. M., Siniscalco, M.: X-linkage of human phosphoglycerate kinase confirmed in man-mouse and man-chinese hamster somatic cell hybrids. Amer. J. hum. Genet. 23, 614–623 (1971)PubMedGoogle Scholar
  81. Migeon, B., Der Kaloustian, V. M., Nyhan, W. L., Young, W. J., Childs, B.: X-linked hypoxanthine-guanine phosphoribosyl transferase deficiency: heterozygote has two clonal populations. Science 160, 425–427 (1968)PubMedGoogle Scholar
  82. Migeon, B. R.: X-linked hypoxanthine-guanine phosphoribosyl transferase deficiency: detection of heterozygotes by selective medium. Biochem. Genet. 4, 377–383 (1970)PubMedGoogle Scholar
  83. Miller, O. J., Cook, P. R., Meera Khan, P., Shin, S., Siniscalco, M.: Mitotic separation of two human X-linked genes in man-mouse somatic cell hybrids. Proc. nat. Acad. Sci. (Wash.) 68, 116–120 (1971)Google Scholar
  84. Mizuno, T., Segaw, M., Kurumada, T., Maruyama, H., Onisawa, J.: Clinical and therapeutic aspects of the Lesch-Nyhan syndrome. Neuropädiatrie 2, 38–52 (1970)Google Scholar
  85. Mizuno, T., Yugari, Y.: Self-mutilation in Lesch-Nyhan syndrome. Lancet 1974 I, 761Google Scholar
  86. Mizuno, T., Yugari, Y.: Prophylactic effect of L-5-hydroxytryptophan on self-mutilation in the Lesch-Nyhan syndrome. Neuropädiatrie 6, 13–23 (1975)Google Scholar
  87. Morrow, J., Colofiore, J., Rintoul, D.: Azaguanine resistant hamster cell lines not deficient in hypoxanthine-guanine phosphoribosyl transferase. J. Cell. Physiol. 81, 97–100 (1973)PubMedGoogle Scholar
  88. Nadler, H. L., Chacko, C. M., Rachmeler, M.: Interallelic complementation in hybrid cells derived from human diploid strains deficient in galactose-1-phosphate uridyl transferase activity. Proc. nat. Acad. Sci. (Wash.) 67, 976–982 (1970)Google Scholar
  89. Nuki, G., Lever, J., Seegmiller, J. E.: Biochemical characteristics of 8-azaguanine resistant human lymphoblast mutants selected in vitro. In: Purine metabolism in man (eds. O. Sperling, A. de Vries, J. B. Wyngaarden), pp. 255–267, New York: Plenum Press 1974Google Scholar
  90. Nyhan, W. L.: Clinical features of the Lesch-Nyhan syndrome: summary of clinical findings. Fed. Proc. 27, 1034–1041 (1968)PubMedGoogle Scholar
  91. Nyhan, W. L.: The Lesch-Nyhan syndrome. Ann. Rev. Med. 24, 41–60 (1973)CrossRefPubMedGoogle Scholar
  92. Nyhan, W. L., Bakay, B., Connor, J. D., Marks, J. F., Keele, D. K.: Hemizygous expression of glucose-6-phosphate dehydrogenase in erythrocytes of heterozygotes for the Lesch-Nyhan syndrome. Proc. nat. Acad. Sci. (Wash.) 65, 214–218 (1970)Google Scholar
  93. Nyhan, W. L., Pesek, J., Sweetman, L., Carpenter, D. G., Garter, C. H.: Genetics of an X-linked recessive inheritance of a syndrome of mental retardation with hyperuricemia. Pediat. Res. 1, 5–13 (1967)Google Scholar
  94. Oei, T. L., de Bruyn, C. H. M. M.: Studies on metabolic cooperation using different types of normal and hypoxanthine-guanine phosphoribosyl transferase (HG-PRT) deficient cells. In: Purine metabolism in man (eds. O. Sperling, A. de Vries, J. B. Wyngaarden) pp. 237–243. New York: Plenum Press 1974Google Scholar
  95. Planet, G., Willemot, J.: Changes in purine phosphoribosyl transferase activities in mouse brain, liver and muscle with age. Biochim. biophys. Acta (Amst.) 364, 236–242 (1974)Google Scholar
  96. Rabinowitz, Y., Schimo, I., Whilhite, B. A.: Metabolic response of separated leucocytes to phytohaemagglutinin: effect of anaerobiasis, actinomycin D and puromycin. Brit. J. Haemat. 15, 455–464 (1968)PubMedGoogle Scholar
  97. Raivio, K. O., Seegmiller, J. E.: Adenine, hypoxanthine and guanine metabolism in fibroblasts from normal individuals and from patients with hypoxanthine-guanine phosphoribosyl transferase deficiency. Biochim. biophys. Acta (Amst.) 299, 273–282 (1973)Google Scholar
  98. Riccardi, V. M., Littlefield, J. W.: Adaption in Lesch-Nyhan cells exposed to aminopterin. Exp. Cell Res. 74, 417–422 (1972)PubMedGoogle Scholar
  99. Ricciuti, F. C., Ruddle, F. H.: Assignment of three gene loci (PGK, HG-PRT, G6PD) to the long arm of the human X-chromosome by somatic cell genetics. Genetics 74, 661–678 (1973)PubMedGoogle Scholar
  100. Richardson, B. J., Ryckman, D. L., Komarnicki, L. M., Hamerton, J. L.: Heterogeneity in the biochemical characteristics of red blood cell hypoxanthine-guanine phosphoribosyl transferase from two unrelated patients with the Lesch-Nyhan syndrome. Biochem. Genet. 9, 197–202 (1973)PubMedGoogle Scholar
  101. Rockson, S., Stone, R., van der Weyden, M., Kelley, W. N.: Lesch-Nyhan syndrome: evidence for abnormal adrenergic function. Science 186, 934–935 (1974)PubMedGoogle Scholar
  102. Rosenbloom, F. M., Henderson, J. F., Caldwell, I. C., Kelley, W. N., Seegmiller, J. E.: Biochemical basis of accelerated purine biosynthesis de novo in human fibroblasts lacking hypoxanthine-guanine phosphoribosyl transferase. J. biol. Chem. 243, 1166–1173 (1968)PubMedGoogle Scholar
  103. Rosenbloom, F. M., Kelley, W. N., Miller, J., Henderson, J. F., Seegmiller, J. E.: Inherited disorder of purine metabolism. Correlation between central nervous system dysfunction and biochemical defects. J. Amer. med. Ass. 202, 175–177 (1967)CrossRefGoogle Scholar
  104. Roos, D., Loos, J. A.: Changes in the carbohydrate metabolism of mitogenically stimulated human peripheral lymphocytes. Biochim. biophys. Acta (Amst.) 222, 565–582 (1970)Google Scholar
  105. Rubin, C. S., Dancis, J., Yip, L. C., Nowinski, R. C., Balis, M. E.: Purification of IMP: pyrophosphate transferase, catalytically incompetent enzymes in Lesch-Nyhan disease. Proc. nat. Acad. Sci. (Wash.) 68, 1461–1464 (1971)Google Scholar
  106. Ruddle, F. H.: Linkage analysis in man using somatic cell hybrids. In: Advances in human genetics (eds. H. Harris, K. Hirschhorn), Vol. III, pp. 173–235. New York: Plenum Press 1972Google Scholar
  107. Sakata, T., Fuchimoto, H.: Stereotyped and aggressive behaviour induced by sustained high dose of theophylline in rats. Jap. J. Pharmacol. 23, 781–786 (1973)PubMedGoogle Scholar
  108. Salzmann, J., De Mars, R., Benke, P.: Single allele expression at an X-linked hyperuricemia locus in heterozygous human cells. Proc. nat. Acad. Sci. (Wash.) 60, 545–552 (1968)Google Scholar
  109. Seegmiller, J. E., Rosenbloom, F. M., Kelley, W. N.: Enzyme defect associated with a sex linked human neurological disorder and excessive purine synthesis. Science 155, 1682–1684 (1967)PubMedGoogle Scholar
  110. Sekiguchi, T., Sekiguchi, F.: Interallelic complementation in hybrid cells derived from Chinese hamster diploid clones deficient in hypoxanthine-guanine phosphoribosyl transferase activity. Exp. Cell Res. 77, 391–403 (1973)PubMedGoogle Scholar
  111. Shapiro, S. L., Sheppard, B. L., Jr., Dreifuss, F. E., Newcombe, D. S.: X-linked recessive inheritance of a syndrome of mental retardation with hyperuricemia. Proc. Soc. exp. Biol. (N.Y.) 122, 609–611 (1966)Google Scholar
  112. Shin, S., Caneva, R., Schildkraut, C. L., Klinger, H. P., Siniscalco, M.: Cells with phosphoribosyl transferase activity recovered from mouse cells resistant to 8-azaguanine. Nature (Lond.) New Biol. 241, 194–196 (1973)Google Scholar
  113. Shin, S., Meera Khan, P., Cook, P. R.: Characterisation of hypoxanthine-guanine phosphoribosyl transferase in man-mouse somatic cell hybrids by an improved electrophoretic method. Biochem. Genet. 5, 91–99 (1971)PubMedGoogle Scholar
  114. Shows, T. B., Brown, J. A.: Human X-linked genes regionally mapped utilizing X-autosome translocations and somatic cell hybrids. Proc. nat. Acad. Sci. (Wash.) 72, 2125–2129 (1975)Google Scholar
  115. Snow, M. H. L., McLaren, A.: The effect of exogenous DNA upon cleaving mouse embryos. Exp. Cell Res. 86, 1–8 (1974)PubMedGoogle Scholar
  116. Sperling, O., Boer, P., Eilam, G., de Vries, A.: Evidence for molecular alteration of erythrocyte hypoxanthine-guanine phosphoribosyl transferase in a gouty family with partial deficiency of the enzyme. Rev. Europ. Etud. Clin. Biol. 17, 72–75 (1972)Google Scholar
  117. Sperling, O., Eilam, G., Schmidt, R., Mundel, G., de Vries, A.: Purine base incorporation into erythrocyte nucleotides inhypoxanthine-guanine phosphoribosyl transferase deficiency. Biochem. Med. 5, 173–176 (1971)PubMedGoogle Scholar
  118. Sperling, O., Frank, M., Ophir, R., Liberman, U. A., Adam, A., de Vries, A.: Partial deficiency of hypoxanthine-guanine phosphoribosyl transferase associated with gout and uric acid lithiasis. Rev. Europ. Etud. Clin. Biol. 15, 942–947 (1970)Google Scholar
  119. Subak-Sharpe, J. H., Bürk, R. R., Pitts, J. D.: Metabolic cooperation by cell to cell transfer between genetically different mammalian cells in tissue culture. Heredity 21, 342–343 (1966)Google Scholar
  120. Stanbridge, E. J., Tischfield, J. A., Schneider, E. L.: Appearance of hypoxanthine-guanine phosphoribosyl transferase activity as a consequence of mycoplasma contamination. Nature (Lond.) 256, 329–331 (1975)Google Scholar
  121. Sweetman, L.: Urinary and cerebrospinal fluid oxypurine levels and allopurinol metabolism in the Lesch-Nyhan syndrome. Fed. Proc. 27, 1055–1059 (1968)PubMedGoogle Scholar
  122. Watson, B., Gormley, I. P., Gardiner, S. E., Evans, H. J., Harris, H.: Reappearance of murine hypoxanthine-guanine phosphoribosyl transferase activity in mouse A9 cells after attempted hybridisation with human cell lines. Exp. Cell Res. 75, 401–409 (1972)PubMedGoogle Scholar
  123. Weiss, M. C., Green, H.: Human-mouse hybrid cell lines containing partial complements of human chromosomes and functioning human genes. Proc. nat. Acad. Sci. (Wash.) 58, 1104–1111 (1967)Google Scholar
  124. Wood, S., Pinsky, L.: Lesch-Nyhan syndrome, rapid detection of heterozygotes. Clin. Genet. 1, 216–219 (1970)Google Scholar
  125. Wullems, G. J., van der Horst, J., Bootsma, D.: Incorporation of isolated chromosomes and induction of hypoxanthine phosphoribosyl transferase in chinese hamster cells. Somat. Cell Genet. 1, 137–152 (1975)PubMedGoogle Scholar
  126. Wyngaarden, J. B., Kelley, W. N.: Gout. In: The metabolic basis of inherited disease (eds. J. B. Stanbury, J. B. Wyngaarden, D. S. Frederickson), 3rd ed., pp. 889–968. New York: McGraw Hill 1972Google Scholar
  127. Yosida, T. H., Sekiguchi, T.: Metaphase figures of rat chromosomes incorporated into mouse cells. Molec. Gen. Genet. 103, 253–257 (1968)PubMedGoogle Scholar
  128. Yü, T., Balis, M. E., Krenitsky, T. A., Dancis, J., Silver, D. N., Elion, G. B., Gutman, A. B.: Rarity of X-linked partial hypoxanthine-guanine phosphoribosyl transferase deficiency in a large gouty population. Ann. intern. Med. 76, 255–264 (1972)PubMedGoogle Scholar
  129. Zee, S. P. M. van der: Het Lesch-Nyhan syndroom. Thesis, Nijmegen 1972Google Scholar
  130. Zeeland, A. A. van, de Ruyter, Y. C. E. M., Simons, J. W. I. M.: The role of 8-azaguanine in the selection from human diploid cells of mutants deficient in hypoxanthine-guanine phosphoribosyl transferase. Mutat. Res. 23, 55–68 (1974)Google Scholar

Copyright information

© Springer-Verlag 1976

Authors and Affiliations

  • Chris H. M. M. de Bruyn
    • 1
  1. 1.Department of Human Genetics, Faculty of MedicineUniversity of NijmegenNijmegenThe Netherlands

Personalised recommendations