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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Jun 15;90(12):5384–5390. doi: 10.1073/pnas.90.12.5384

Gaucher disease as a paradigm of current issues regarding single gene mutations of humans.

E Beutler 1
PMCID: PMC46724  PMID: 8516282

Abstract

Gaucher disease is a glycolytic storage disease caused by a deficiency in activity of the catabolic enzyme glucocerebrosidase. Over 35 different mutations have been documented, including missense and nonsense point mutations, splicing mutations, deletions and insertions, a fusion gene, and examples of gene conversion. Gaucher disease is most common in the Ashkenazi Jewish population, in which just five of the mutations in this population account for 98% of the disease-producing alleles. Each of these mutations is found in the context of a single haplotype, a finding consistent with a single origin of each mutation. Although it is clear that these mutations provide a selective advantage in the Jewish population and thus constitute a balanced polymorphism, the nature of the advantage is unknown. Gaucher disease can be treated symptomatically, by administration of the missing enzyme, by allogeneic bone marrow transplantation, and potentially by gene transfer into hematopoietic stem cells. Increasing understanding of this disease has, as in other genetic disorders, created a host of social and ethical dilemmas regarding matters such as the cost of treatment for rare diseases and the advantages and disadvantages of population-targeted genetic screening.

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Selected References

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  1. Achord D., Brot F., Gonzalez-Noriega A., Sly W., Stahl P. Human beta-glucuronidase. II. Fate of infused human placental beta-glucuronidase in the rat. Pediatr Res. 1977 Jul;11(7):816–822. doi: 10.1203/00006450-197707000-00008. [DOI] [PubMed] [Google Scholar]
  2. Ashwell G., Morell A. G. The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins. Adv Enzymol Relat Areas Mol Biol. 1974;41(0):99–128. doi: 10.1002/9780470122860.ch3. [DOI] [PubMed] [Google Scholar]
  3. BRADY R. O., KANFER J. N., SHAPIRO D. METABOLISM OF GLUCOCEREBROSIDES. II. EVIDENCE OF AN ENZYMATIC DEFICIENCY IN GAUCHER'S DISEASE. Biochem Biophys Res Commun. 1965 Jan 18;18:221–225. doi: 10.1016/0006-291x(65)90743-6. [DOI] [PubMed] [Google Scholar]
  4. Barneveld R. A., Keijzer W., Tegelaers F. P., Ginns E. I., Geurts van Kessel A., Brady R. O., Barranger J. A., Tager J. M., Galjaard H., Westerveld A. Assignment of the gene coding for human beta-glucocerebrosidase to the region q21-q31 of chromosome 1 using monoclonal antibodies. Hum Genet. 1983;64(3):227–231. doi: 10.1007/BF00279398. [DOI] [PubMed] [Google Scholar]
  5. Barton N. W., Brady R. O., Dambrosia J. M., Di Bisceglie A. M., Doppelt S. H., Hill S. C., Mankin H. J., Murray G. J., Parker R. I., Argoff C. E. Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher's disease. N Engl J Med. 1991 May 23;324(21):1464–1470. doi: 10.1056/NEJM199105233242104. [DOI] [PubMed] [Google Scholar]
  6. Barton N. W., Furbish F. S., Murray G. J., Garfield M., Brady R. O. Therapeutic response to intravenous infusions of glucocerebrosidase in a patient with Gaucher disease. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1913–1916. doi: 10.1073/pnas.87.5.1913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Belchetz P. E., Crawley J. C., Braidman I. P., Gregoriadis G. Treatment of Gaucher's disease with liposome-entrapped glucocerebroside: beta-glucosidase. Lancet. 1977 Jul 16;2(8029):116–117. doi: 10.1016/s0140-6736(77)90123-4. [DOI] [PubMed] [Google Scholar]
  8. Beutler E. Bone marrow transplantation for sickle cell anemia: summarizing comments. Semin Hematol. 1991 Jul;28(3):263–267. [PubMed] [Google Scholar]
  9. Beutler E., Dale G. L., Guinto D. E., Kuhl W. Enzyme replacement therapy in Gaucher's disease: preliminary clinical trial of a new enzyme preparation. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4620–4623. doi: 10.1073/pnas.74.10.4620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Beutler E., Dale G. L., Kuhl W. Repacement therapy in Gaucher disease. Birth Defects Orig Artic Ser. 1980;16(1):369–381. [PubMed] [Google Scholar]
  11. Beutler E. Gaucher disease: new molecular approaches to diagnosis and treatment. Science. 1992 May 8;256(5058):794–799. doi: 10.1126/science.1589760. [DOI] [PubMed] [Google Scholar]
  12. Beutler E. Gaucher's disease. N Engl J Med. 1991 Nov 7;325(19):1354–1360. doi: 10.1056/NEJM199111073251906. [DOI] [PubMed] [Google Scholar]
  13. Beutler E., Gelbart T. Gaucher disease associated with a unique KpnI restriction site: identification of the amino-acid substitution. Ann Hum Genet. 1990 May;54(Pt 2):149–153. doi: 10.1111/j.1469-1809.1990.tb00371.x. [DOI] [PubMed] [Google Scholar]
  14. Beutler E., Gelbart T., Kuhl W., Sorge J., West C. Identification of the second common Jewish Gaucher disease mutation makes possible population-based screening for the heterozygous state. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10544–10547. doi: 10.1073/pnas.88.23.10544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Beutler E., Gelbart T., Kuhl W., Zimran A., West C. Mutations in Jewish patients with Gaucher disease. Blood. 1992 Apr 1;79(7):1662–1666. [PubMed] [Google Scholar]
  16. Beutler E., Gelbart T., West C. Identification of six new Gaucher disease mutations. Genomics. 1993 Jan;15(1):203–205. doi: 10.1006/geno.1993.1035. [DOI] [PubMed] [Google Scholar]
  17. Beutler E., Kay A., Saven A., Garver P., Thurston D., Dawson A., Rosenbloom B. Enzyme replacement therapy for Gaucher disease. Blood. 1991 Sep 1;78(5):1183–1189. [PubMed] [Google Scholar]
  18. Beutler E., Kuhl W. Detection of the defect of Gaucher's disease and its carrier state in peripheral-blood leucocytes. Lancet. 1970 Mar 21;1(7647):612–613. doi: 10.1016/s0140-6736(70)91646-6. [DOI] [PubMed] [Google Scholar]
  19. Beutler E. The biochemical genetics of the hexosaminidase system in man. Am J Hum Genet. 1979 Mar;31(2):95–105. [PMC free article] [PubMed] [Google Scholar]
  20. Beutler E., West C., Gelbart T. Polymorphisms in the human glucocerebrosidase gene. Genomics. 1992 Apr;12(4):795–800. doi: 10.1016/0888-7543(92)90311-f. [DOI] [PubMed] [Google Scholar]
  21. Blitzer M. G., McDowell G. A. Tay-Sachs disease as a model for screening inborn errors. Clin Lab Med. 1992 Sep;12(3):463–480. [PubMed] [Google Scholar]
  22. Bodine D. M., McDonagh K. T., Brandt S. J., Ney P. A., Agricola B., Byrne E., Nienhuis A. W. Development of a high-titer retrovirus producer cell line capable of gene transfer into rhesus monkey hematopoietic stem cells. Proc Natl Acad Sci U S A. 1990 May;87(10):3738–3742. doi: 10.1073/pnas.87.10.3738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Brady R. O., Gal A. E., Pentchev P. G. Evolution of enzyme replacement therapy for lipid storage diseases. Life Sci. 1974 Oct 1;15(7):1235–1248. doi: 10.1016/0024-3205(74)90305-1. [DOI] [PubMed] [Google Scholar]
  24. Brady R. O., Pentchev P. G., Gal A. E., Hibbert S. R., Dekaban A. S. Replacement therapy for inherited enzyme deficiency. Use of purified glucocerebrosidase in Gaucher's disease. N Engl J Med. 1974 Nov 7;291(19):989–993. doi: 10.1056/NEJM197411072911901. [DOI] [PubMed] [Google Scholar]
  25. Brady R. O., Pentchev P. G., Gal A. G. Investigations in enzyme replacement therapy in lipid storage diseases. Fed Proc. 1975 Apr;34(5):1310–1315. [PubMed] [Google Scholar]
  26. Choudary P. V., Tsuji S., Martin B. M., Guild B. C., Mulligan R. C., Murray G. J., Barranger J. A., Ginns E. I. The molecular biology of Gaucher disease and the potential for gene therapy. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 2):1047–1052. doi: 10.1101/sqb.1986.051.01.121. [DOI] [PubMed] [Google Scholar]
  27. Collins A., Keats B. J., Dracopoli N., Shields D. C., Morton N. E. Integration of gene maps: chromosome 1. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4598–4602. doi: 10.1073/pnas.89.10.4598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Correll P. H., Colilla S., Dave H. P., Karlsson S. High levels of human glucocerebrosidase activity in macrophages of long-term reconstituted mice after retroviral infection of hematopoietic stem cells. Blood. 1992 Jul 15;80(2):331–336. [PubMed] [Google Scholar]
  29. Correll P. H., Fink J. K., Brady R. O., Perry L. K., Karlsson S. Production of human glucocerebrosidase in mice after retroviral gene transfer into multipotential hematopoietic progenitor cells. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8912–8916. doi: 10.1073/pnas.86.22.8912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. DEDUVE C. FROM CYTASES TO LYSOSOMES. Fed Proc. 1964 Sep-Oct;23:1045–1049. [PubMed] [Google Scholar]
  31. Dale G. L., Beutler E. Enzyme replacement therapy in Gaucher's disease: a rapid, high-yield method for purification of glucocerebrosidase. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4672–4674. doi: 10.1073/pnas.73.12.4672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Doebber T. W., Wu M. S., Bugianesi R. L., Ponpipom M. M., Furbish F. S., Barranger J. A., Brady R. O., Shen T. Y. Enhanced macrophage uptake of synthetically glycosylated human placental beta-glucocerebrosidase. J Biol Chem. 1982 Mar 10;257(5):2193–2199. [PubMed] [Google Scholar]
  33. Eyal N., Firon N., Wilder S., Kolodny E. H., Horowitz M. Three unique base pair changes in a family with Gaucher disease. Hum Genet. 1991 Jul;87(3):328–332. doi: 10.1007/BF00200914. [DOI] [PubMed] [Google Scholar]
  34. Eyal N., Wilder S., Horowitz M. Prevalent and rare mutations among Gaucher patients. Gene. 1990 Dec 15;96(2):277–283. doi: 10.1016/0378-1119(90)90264-r. [DOI] [PubMed] [Google Scholar]
  35. Fairbanks V. F., Nepo A. G., Beutler E., Dickson E. R., Honig G. Glucose-6-phosphate dehydrogenase variants: reexamination of G6PD Chicago and Cornell and a new variant (G6PD Pea Ridge) resembling G6PD Chicago. Blood. 1980 Feb;55(2):216–220. [PubMed] [Google Scholar]
  36. Fallet S., Grace M. E., Sibille A., Mendelson D. S., Shapiro R. S., Hermann G., Grabowski G. A. Enzyme augmentation in moderate to life-threatening Gaucher disease. Pediatr Res. 1992 May;31(5):496–502. doi: 10.1203/00006450-199205000-00018. [DOI] [PubMed] [Google Scholar]
  37. Figueroa M. L., Rosenbloom B. E., Kay A. C., Garver P., Thurston D. W., Koziol J. A., Gelbart T., Beutler E. A less costly regimen of alglucerase to treat Gaucher's disease. N Engl J Med. 1992 Dec 3;327(23):1632–1636. doi: 10.1056/NEJM199212033272304. [DOI] [PubMed] [Google Scholar]
  38. Furbish F. S., Steer C. J., Krett N. L., Barranger J. A. Uptake and distribution of placental glucocerebrosidase in rat hepatic cells and effects of sequential deglycosylation. Biochim Biophys Acta. 1981 Apr 3;673(4):425–434. doi: 10.1016/0304-4165(81)90474-8. [DOI] [PubMed] [Google Scholar]
  39. Gale R. P., Sparkes R. S., Golde D. W. Bone marrow origin of hepatic macrophages (Kupffer cells) in humans. Science. 1978 Sep 8;201(4359):937–938. doi: 10.1126/science.356266. [DOI] [PubMed] [Google Scholar]
  40. Ginns E. I., Choudary P. V., Tsuji S., Martin B., Stubblefield B., Sawyer J., Hozier J., Barranger J. A. Gene mapping and leader polypeptide sequence of human glucocerebrosidase: implications for Gaucher disease. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7101–7105. doi: 10.1073/pnas.82.20.7101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Goldman D. P., Clarke A. E., Garber A. M. Creating the costliest orphan. The Orphan Drug Act in the development of Ceredase. Int J Technol Assess Health Care. 1992 Fall;8(4):583–597. doi: 10.1017/s0266462300002294. [DOI] [PubMed] [Google Scholar]
  42. Graves P. N., Grabowski G. A., Eisner R., Palese P., Smith F. I. Gaucher disease type 1: cloning and characterization of a cDNA encoding acid beta-glucosidase from an Ashkenazi Jewish patient. DNA. 1988 Oct;7(8):521–528. doi: 10.1089/dna.1.1988.7.521. [DOI] [PubMed] [Google Scholar]
  43. He G. S., Grabowski G. A. Gaucher disease: A G+1----A+1 IVS2 splice donor site mutation causing exon 2 skipping in the acid beta-glucosidase mRNA. Am J Hum Genet. 1992 Oct;51(4):810–820. [PMC free article] [PubMed] [Google Scholar]
  44. He G. S., Grace M. E., Grabowski G. A. Gaucher disease: four rare alleles encoding F213I, P289L, T323I, and R463C in type 1 variants. Hum Mutat. 1992;1(5):423–427. doi: 10.1002/humu.1380010513. [DOI] [PubMed] [Google Scholar]
  45. Hickey W. F., Kimura H. Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science. 1988 Jan 15;239(4837):290–292. doi: 10.1126/science.3276004. [DOI] [PubMed] [Google Scholar]
  46. Hobbs J. R., Jones K. H., Shaw P. J., Lindsay I., Hancock M. Beneficial effect of pre-transplant splenectomy on displacement bone marrow transplantation for Gaucher's syndrome. Lancet. 1987 May 16;1(8542):1111–1115. doi: 10.1016/s0140-6736(87)91673-4. [DOI] [PubMed] [Google Scholar]
  47. Hong C. M., Ohashi T., Yu X. J., Weiler S., Barranger J. A. Sequence of two alleles responsible for Gaucher disease. DNA Cell Biol. 1990 May;9(4):233–241. doi: 10.1089/dna.1990.9.233. [DOI] [PubMed] [Google Scholar]
  48. Horowitz M., Wilder S., Horowitz Z., Reiner O., Gelbart T., Beutler E. The human glucocerebrosidase gene and pseudogene: structure and evolution. Genomics. 1989 Jan;4(1):87–96. doi: 10.1016/0888-7543(89)90319-4. [DOI] [PubMed] [Google Scholar]
  49. Kampine J. P., Brady R. O., Kanfer J. N., Feld M., Shapiro D. Diagnosis of gaucher's disease and niemann-pick disease with small samples of venous blood. Science. 1967 Jan 6;155(3758):86–88. doi: 10.1126/science.155.3758.86. [DOI] [PubMed] [Google Scholar]
  50. Kawame H., Eto Y. A new glucocerebrosidase-gene missense mutation responsible for neuronopathic Gaucher disease in Japanese patients. Am J Hum Genet. 1991 Dec;49(6):1378–1380. [PMC free article] [PubMed] [Google Scholar]
  51. Kawame H., Hasegawa Y., Eto Y., Maekawa K. Rapid identification of mutations in the glucocerebrosidase gene of Gaucher disease patients by analysis of single-strand conformation polymorphisms. Hum Genet. 1992 Nov;90(3):294–296. doi: 10.1007/BF00220082. [DOI] [PubMed] [Google Scholar]
  52. Kay A. C., Saven A., Garver P., Thurston D. W., Rosenbloom B. F., Beutler E. Enzyme replacement therapy in type I Gaucher disease. Trans Assoc Am Physicians. 1991;104:258–264. [PubMed] [Google Scholar]
  53. Kohn D. B., Nolta J. A., Weinthal J., Bahner I., Yu X. J., Lilley J., Crooks G. M. Toward gene therapy for Gaucher disease. Hum Gene Ther. 1991 Summer;2(2):101–105. doi: 10.1089/hum.1991.2.2-101. [DOI] [PubMed] [Google Scholar]
  54. Latham T. E., Theophilus B. D., Grabowski G. A., Smith F. I. Heterogeneity of mutations in the acid beta-glucosidase gene of Gaucher disease patients. DNA Cell Biol. 1991 Jan-Feb;10(1):15–21. doi: 10.1089/dna.1991.10.15. [DOI] [PubMed] [Google Scholar]
  55. Latham T., Grabowski G. A., Theophilus B. D., Smith F. I. Complex alleles of the acid beta-glucosidase gene in Gaucher disease. Am J Hum Genet. 1990 Jul;47(1):79–86. [PMC free article] [PubMed] [Google Scholar]
  56. Nagel R. L. Innate resistance to malaria: the intraerythrocytic cycle. Blood Cells. 1990;16(2-3):321–349. [PubMed] [Google Scholar]
  57. Nagel R. L. Severity, pathobiology, epistatic effects, and genetic markers in sickle cell anemia. Semin Hematol. 1991 Jul;28(3):180–201. [PubMed] [Google Scholar]
  58. Nolta J. A., Sender L. S., Barranger J. A., Kohn D. B. Expression of human glucocerebrosidase in murine long-term bone marrow cultures after retroviral vector-mediated transfer. Blood. 1990 Feb 1;75(3):787–797. [PubMed] [Google Scholar]
  59. Nolta J. A., Yu X. J., Bahner I., Kohn D. B. Retroviral-mediated transfer of the human glucocerebrosidase gene into cultured Gaucher bone marrow. J Clin Invest. 1992 Aug;90(2):342–348. doi: 10.1172/JCI115868. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Orita M., Iwahana H., Kanazawa H., Hayashi K., Sekiya T. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2766–2770. doi: 10.1073/pnas.86.8.2766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Pentchev P. G., Brady R. O., Hibbert S. R., Gal A. E., Shapiro D. Isolation and characterization of glucocerebrosidase from human placental tissue. J Biol Chem. 1973 Aug 10;248(15):5256–5261. [PubMed] [Google Scholar]
  62. Powars D. R. Sickle cell anemia: beta s-gene-cluster haplotypes as prognostic indicators of vital organ failure. Semin Hematol. 1991 Jul;28(3):202–208. [PubMed] [Google Scholar]
  63. Rappeport J. M., Ginns E. I. Bone-marrow transplantation in severe Gaucher's disease. N Engl J Med. 1984 Jul 12;311(2):84–88. doi: 10.1056/NEJM198407123110203. [DOI] [PubMed] [Google Scholar]
  64. Reiner O., Wigderson M., Horowitz M. Structural analysis of the human glucocerebrosidase genes. DNA. 1988 Mar;7(2):107–116. doi: 10.1089/dna.1988.7.107. [DOI] [PubMed] [Google Scholar]
  65. Rotter J. I., Diamond J. M. What maintains the frequencies of human genetic diseases? Nature. 1987 Sep 24;329(6137):289–290. doi: 10.1038/329289a0. [DOI] [PubMed] [Google Scholar]
  66. Sato Y., Beutler E. Binding, internalization, and degradation of mannose-terminated glucocerebrosidase by macrophages. J Clin Invest. 1993 May;91(5):1909–1917. doi: 10.1172/JCI116409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Shafit-Zagardo B., Devine E. A., Smith M., Arredondo-Vega F., Desnick R. J. Assignment of the gene for acid beta-glucosidase to human chromosome 1. Am J Hum Genet. 1981 Jul;33(4):564–575. [PMC free article] [PubMed] [Google Scholar]
  68. Sidransky E., Tsuji S., Martin B. M., Stubblefield B., Ginns E. I. DNA mutation analysis of Gaucher patients. Am J Med Genet. 1992 Feb 1;42(3):331–336. doi: 10.1002/ajmg.1320420315. [DOI] [PubMed] [Google Scholar]
  69. Smith R. M., Curnutte J. T. Molecular basis of chronic granulomatous disease. Blood. 1991 Feb 15;77(4):673–686. [PubMed] [Google Scholar]
  70. Sorge J. A., West C., Kuhl W., Treger L., Beutler E. The human glucocerebrosidase gene has two functional ATG initiator codons. Am J Hum Genet. 1987 Dec;41(6):1016–1024. [PMC free article] [PubMed] [Google Scholar]
  71. Sorge J., Gelbart T., West C., Westwood B., Beutler E. Heterogeneity in type I Gaucher disease demonstrated by restriction mapping of the gene. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5442–5445. doi: 10.1073/pnas.82.16.5442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Sorge J., Gross E., West C., Beutler E. High level transcription of the glucocerebrosidase pseudogene in normal subjects and patients with Gaucher disease. J Clin Invest. 1990 Oct;86(4):1137–1141. doi: 10.1172/JCI114818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Sorge J., Kuhl W., West C., Beutler E. Complete correction of the enzymatic defect of type I Gaucher disease fibroblasts by retroviral-mediated gene transfer. Proc Natl Acad Sci U S A. 1987 Feb;84(4):906–909. doi: 10.1073/pnas.84.4.906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Sorge J., Kuhl W., West C., Beutler E. Gaucher disease: retrovirus-mediated correction of the enzymatic defect in cultured cells. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 2):1041–1046. doi: 10.1101/sqb.1986.051.01.120. [DOI] [PubMed] [Google Scholar]
  75. Sorge J., West C., Westwood B., Beutler E. Molecular cloning and nucleotide sequence of human glucocerebrosidase cDNA. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7289–7293. doi: 10.1073/pnas.82.21.7289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Svennerholm L., Erikson A., Groth C. G., Ringdén O., Månsson J. E. Norrbottnian type of Gaucher disease--clinical, biochemical and molecular biology aspects: successful treatment with bone marrow transplantation. Dev Neurosci. 1991;13(4-5):345–351. doi: 10.1159/000112184. [DOI] [PubMed] [Google Scholar]
  77. Theophilus B. D., Latham T., Grabowski G. A., Smith F. I. Comparison of RNase A, a chemical cleavage and GC-clamped denaturing gradient gel electrophoresis for the detection of mutations in exon 9 of the human acid beta-glucosidase gene. Nucleic Acids Res. 1989 Oct 11;17(19):7707–7722. doi: 10.1093/nar/17.19.7707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Thomas E. D., Ramberg R. E., Sale G. E., Sparkes R. S., Golde D. W. Direct evidence for a bone marrow origin of the alveolar macrophage in man. Science. 1976 Jun 4;192(4243):1016–1018. doi: 10.1126/science.775638. [DOI] [PubMed] [Google Scholar]
  79. Tsai P., Lipton J. M., Sahdev I., Najfeld V., Rankin L. R., Slyper A. H., Ludman M., Grabowski G. A. Allogenic bone marrow transplantation in severe Gaucher disease. Pediatr Res. 1992 May;31(5):503–507. doi: 10.1203/00006450-199205000-00019. [DOI] [PubMed] [Google Scholar]
  80. Tsuji S., Choudary P. V., Martin B. M., Stubblefield B. K., Mayor J. A., Barranger J. A., Ginns E. I. A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher's disease. N Engl J Med. 1987 Mar 5;316(10):570–575. doi: 10.1056/NEJM198703053161002. [DOI] [PubMed] [Google Scholar]
  81. Tsuji S., Choudary P. V., Martin B. M., Winfield S., Barranger J. A., Ginns E. I. Nucleotide sequence of cDNA containing the complete coding sequence for human lysosomal glucocerebrosidase. J Biol Chem. 1986 Jan 5;261(1):50–53. [PubMed] [Google Scholar]
  82. Tsuji S., Martin B. M., Barranger J. A., Stubblefield B. K., LaMarca M. E., Ginns E. I. Genetic heterogeneity in type 1 Gaucher disease: multiple genotypes in Ashkenazic and non-Ashkenazic individuals. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2349–2352. doi: 10.1073/pnas.85.7.2349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Tybulewicz V. L., Tremblay M. L., LaMarca M. E., Willemsen R., Stubblefield B. K., Winfield S., Zablocka B., Sidransky E., Martin B. M., Huang S. P. Animal model of Gaucher's disease from targeted disruption of the mouse glucocerebrosidase gene. Nature. 1992 Jun 4;357(6377):407–410. doi: 10.1038/357407a0. [DOI] [PubMed] [Google Scholar]
  84. Wigderson M., Firon N., Horowitz Z., Wilder S., Frishberg Y., Reiner O., Horowitz M. Characterization of mutations in Gaucher patients by cDNA cloning. Am J Hum Genet. 1989 Mar;44(3):365–377. [PMC free article] [PubMed] [Google Scholar]
  85. Zimran A., Kay A., Gelbart T., Garver P., Thurston D., Saven A., Beutler E. Gaucher disease. Clinical, laboratory, radiologic, and genetic features of 53 patients. Medicine (Baltimore) 1992 Nov;71(6):337–353. [PubMed] [Google Scholar]
  86. Zimran A., Sorge J., Gross E., Kubitz M., West C., Beutler E. A glucocerebrosidase fusion gene in Gaucher disease. Implications for the molecular anatomy, pathogenesis, and diagnosis of this disorder. J Clin Invest. 1990 Jan;85(1):219–222. doi: 10.1172/JCI114415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Zimran A., Sorge J., Gross E., Kubitz M., West C., Beutler E. Prediction of severity of Gaucher's disease by identification of mutations at DNA level. Lancet. 1989 Aug 12;2(8659):349–352. doi: 10.1016/s0140-6736(89)90536-9. [DOI] [PubMed] [Google Scholar]
  88. van Beusechem V. W., Kukler A., Heidt P. J., Valerio D. Long-term expression of human adenosine deaminase in rhesus monkeys transplanted with retrovirus-infected bone-marrow cells. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7640–7644. doi: 10.1073/pnas.89.16.7640. [DOI] [PMC free article] [PubMed] [Google Scholar]

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