Discrepancies between genotype and phenotype in hematology: An important frontier

Blood

Volumn 98, Issue 9, 2001, Pages 2597-2602

  Beutler, Ernest ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; GLUCOSE 6 PHOSPHATE DEHYDROGENASE; GLUCOSYLCERAMIDASE;

AUTOSOMAL RECESSIVE DISORDER; BLOOD CLOTTING DISORDER; CLINICAL FEATURE; DISEASE SEVERITY; GAUCHER DISEASE; GENE MUTATION; GENETIC DISORDER; GENOTYPE PHENOTYPE CORRELATION; GLUCOSE 6 PHOSPHATE DEHYDROGENASE DEFICIENCY; HEMATOLOGIC DISEASE; HEMOCHROMATOSIS; HOMOZYGOSITY; HUMAN; PHENOTYPIC VARIATION; PRIORITY JOURNAL; REVIEW; SEQUENCE ANALYSIS; SICKLE CELL ANEMIA;

EID: 0035525732     PISSN: 00064971     EISSN: None     Source Type: Journal    
DOI: 10.1182/blood.V98.9.2597     Document Type: Review

References (85)

1. Serjeant G, Serjeant B, Stephens A, et al. Determinants of haemoglobin level in steady-state homozygous sickle cell disease. Br J Haematol 1996;92:143-149.
2. Beutler E. The effect of methemoglobin formation in sickle cell disease. J Clin Invest. 1961;40:1856-1871.
3. Powars DR, Weiss JN, Chan LS, Schroeder WA. Is there a threshold level of fetal hemoglobin that ameliorates morbidity in sickle cell anemia? Blood. 1984;63:921-926.
4. El-Hazmi MAF, Al-Swailem AR, Bahakim HM, AlFaleh FZ, Warsy AS. Effect of alpha thalassaemia, G-6-PD deficiency and Hb F on the nature of sickle cell anaemia in south-western Saudi Arabia. Trop Geogr Med. 1990;42:241-247.
5. Green NS, Fabry ME, Kaptue-Noche L, Nagel RL. Senegal haplotype is associated with higher HbF than Benin and Cameroon haplotypes in African children with sickle cell anemia. Am J Hematol. 1993;44:145-146.
6. Steinberg MH. Sickle cell anemia and fetal hemoglobin. Am J Med Sci. 1994;308:259-265.
7. Platt OS, Thorington BD, Brambilla DJ, et al. Pain in sickle cell disease - rates and risk factors. N Engl J Med. 1991;325:11-16.
8. Thein SL, Craig JE. Genetics of Hb F/F cell variance in adults and heterocellular hereditary persistence of fetal hemoglobin. Hemoglobin. 1998;22:401-414.
9. Beutler E, Paniker NV, West C. The effect of 2,3DPG on the sickling phenomenon. Blood. 1971;37:184-186.
10. 2 dissociation curve and sickling; a general formulation and therapeutic strategy. Blood. 1974;43:297-300.
11. Poillon WN, Kim BC. 2,3-Diphosphoglycerate and intracellular pH as interdependent determinants of the physiologic solubility of deoxyhemoglobin S. Blood. 1990;76:1028-1036.
12. Charache S, Grisolia S, Fiedler AJ, Heliegers AE, Effect of 2,3-diphosphoglycerate on oxygen affinity of blood in sickle cell anemia. J Clin Invest. 1970;49:806-812.
13. Cohen-Solal M, Préhu C, Wajcman H, et al. A new sickle cell disease phenotype associating Hb S trait, severe pyruvate kinase deficiency (PK Conakry), and an α2 globin gene variant (Hb Conakry). Br J Haematol. 1998;103:950-956.
14. Embury SH, Dozy AM, Miller J, et al. Concurrent sickle-cell anemia and alpha-thalassemia: effect on severity of anemia. N Engl J Med. 1982;306:270-274.
15. Nagel RL, Ranney HM. Genetic epidemiology of structural mutations of the beta-globin gene. Semin Hematol. 1990;27:342-359.
16. Beutler E. G6PD deficiency. Blood. 1994;84:3613-3636.
17. Ohno S, Kaplan WD, Kinosita R. On isopycnotic behavior of the XX-bivalent in oocytes of Rattus norvegicus. Exp Cell Res. 1960;19:637-639.
18. Beutler E, Yeh M, Fairbanks VF. The normal human female as a mosaic of X-chromosome activity: studies using the gene for G-6-PD deficiency as a marker. Proc Natl Acad Sci U S A. 1962;48:9-16.
19. Lyon MF. Gene action in the X-chromosome of the mouse (Mus musculus I). Nature. 1961;190:372-373.
20. Willard HF. X chromosome inactivation, XIST, and pursuit of the X-inactivation center. Cell. 1996;86:5-7.
21. Dern RJ, Beutler E, Alving AS. The hemolytic effect of primaquine, V: primaquine sensitivity as a manifestation of a multiple drug sensitivity. J Lab Clin Med. 1955;45:30-39.
22. Magon AM, Leipzig RM, Zannoni VG, Brewer GJ. Interactions of glucose-6-phosphate dehydrogenase deficiency with drug acetylation and hydroxylation reactions. J Lab Clin Med. 1981;97:764-770.
23. Stamatoyannopoulos G, Fraser GR, Motulsky AG, Fessas P, Akrivakis A, Papayannopoulou T. On the familial predisposition to favism. Am J Hum Genet. 1966;18:253-263.
24. Bottini E, Lucarelli P, Agostino R, Palmarino R, Bosinco L, Antognoni G. Favism: association with erythrocyte acid phosphatase phenotype. Science. 1971;171:409-411.
25. Cassimos CHR, Malaka-Zafiriu K, Tsiures J. Urinary d-glucaric acid excretion in normal and G-6-PD-deficient children with favism. J Pediatr. 1974;84:871-872.
26. Cutillo S, Costa S, Vintuleddu MC, Meloni T. Salicylamide-glucuronide formation in children with favism and in their parents. Acta Haematol (Basel). 1976;55:296-299.
27. Mavelli I, Ciriolo MR, Rossi L, et al. Favism: a hemolytic disease associated with increased superoxide dismutase and decreased glutathione peroxidase activities in red blood cells. Eur J Biochem. 1984;139:13-18.
28. Monaghan G, Ryan M, Seddon R, Hume R, Burchell B. Genetic variation in bilirubin UDP-glucuronosyltransferase gene promotor and Gilbert's syndrome. Lancet. 1996;347:578-581.
29. Kaplan M, Renbaum P, Levy-Lahad E, Hammerman C, Lahad A, Beutler E. Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: a dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia. Proc Natl Acad Sci U S A. 1997;94:12128-12132.
30. Galanello R, Cipollina MD, Carboni G, et al. Hyperbilirubinemia, glucose-6-phosphate-dehydrogenase deficiency and Gilbert's syndrome. Eur J Pediatr. 1999;158:914-916.
31. Perrotta S, Del Giudice EM, Carbone R, et al. Gilbert's syndrome accounts for the phenotypic variability of congenital dyserythropoietic anemia type II (CDA-II). J Pediatr. 2000;136:556-559.
32. Iolascon A, Faienza MF, Moretti A, Perrotta S, Del Giudice EM. UGT1 promoter polymorphism accounts for increased neonatal appearance of hereditary spherocytosis. Blood. 1998;91:1093-1094.
33. Del Giudice EM, Perrotta S, Nobili B, Specchia C, d'Urzo G, Iolascon A. Coinheritance of Gilbert syndrome increases the risk for developing gallstones in patients with hereditary spherocytosis. Blood. 1999;94:2259-2262.
34. Iolascon A, Faienza MF, Giordani L, et al. Bilirubin-levels in the acute hemolytic crisis of G6PD deficiency are related to Gilbert's syndrome. Eur J Haematol. 1999;62:307-310.
35. Daneman A, Stringer D, Reilly BJ. Neonatal ascites due to lysosomal storage disease. Radiology. 1983;149:463-467.
36. Ginsburg SJ, Groll M. Hydrops fetalis due to infantile Gaucher's disease. J Pediatr. 1973;82:1046-1048.
37. Sun CC, Panny S, Combs J, Gutberlett R. Hydrops fetalis associated with Gaucher disease. Pathol Res Pract. 1984;179:101-104.
38. Berrebi A, Wishnitzer R, Von der Walde U. Gauchers disease: unexpected diagnosis in three patients over seventy years old. Nouv Rev Fr Hematol. 1984;26:201-203.
39. Chang-Lo M, Yam LT. Gaucher's disease: review of the literature and report of twelve new cases. Am J Med Sci. 1967;254:303-315.
40. Kolodny EH, Ullman MD, Mankin HJ, Raghavan SS, Topol J, Sullivan JL. Phenotypic manifestations of Gaucher disease: clinical features in 48 biochemically verified type I patients and comment on type II patients. In: Desnick RJ, Gatt S, Grabowski GA, eds. Gaucher Disease: A Century of Delineation and Research. New York, NY: Alan R. Liss, Inc; 1982:33-65.
41. Aerts JMFG, Donker-Koopman WE, van Laar C, et al. Relationship between the two immunologically distinguishable forms of glucocerebrosidase in tissue extracts. Eur J Biochem. 1987;163:583-589.
42. van Weely S, Van den Berg M, Barranger JA, Sa Miranda MC, Tager JM, Aerts JMFG. Role of pH in determining the cell type-specific residual activity of glucocerebrosidase in type 1 Gaucher disease. J Clin Invest. 1993;91:1167-1175.
43. Sheldon JH. Haemochromatosis. London, England: Oxford University Press; 1935.
44. Bulaj ZJ, Edwards CQ, Ajioka RS, Phillips JD, Kushner JP. Frequency of disease-related morbidity in 214 clinically unselected hemochromatosis homozygotes [abstract]. Blood. 1999;94(suppl 1):644.
45. Olynyk JK, Cullen DJ, Aquilia S, Rossi E, Summerville L, Powell LW. A population-based study of the clinical expression of the hemochromatosis gene. N Engl J Med. 1999;341:718-724.
46. Beutler E, Felitti VJ, Koziol JA, Ho N, Gelbart T. Penetrance of the 845G6A (C282Y) HFE hereditary hemochromatosis mutation. Lancet. In press.
47. Willis G, Fellows IW, Wimperis JZ. Deaths attributed to haemochromatosis are rare in Britain [abstract]. BMJ. 2000;320:1146
48. Willis G, Wimperis JZ, Lonsdale R, et al. Incidence of liver disease in people with HFE mutations. Gut. 2000;46:401-404.
49. Willis G, Wimperis JZ, Smith KC, Fellows IW, Jennings BA. Haemochromatosis gene C282Y homozygotes in an elderly male population. Lancet. 1999;354:221-222.
50. Olsson KS, Säfwenberg J, Ritter B. The effect of iron fortification of the diet on clinical iron overload in the general population. Ann N Y Acad Sci. 1988;526:290-300.
51. Bahram S, Gilfillan S, Kuhn LC, et al. Experimental hemochromatosis due to MHC class I HFE deficiency: immune status and iron metabolism. Proc Natl Acad Sci U S A. 1999;96:13312-13317.
52. Levy JE, Montross LK, Andrews NC. Genes that modify the hemochromatosis phenotype in mice. J Clin Invest. 2000;105:1209-1216.
53. Feder JN, Gnirke A, Thomas W, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet. 1996;13:399-408.
54. Beutler E, West C. New diallelic markers in the HLA region of chromosome 6. Blood Cells Mol Dis. 1997;23:219-229.
55. de Sousa M, Reimao R, Lacerda R, Hugo P, Kaufmann SH, Porto G. Iron overload in beta 2-microglobulin-deficient mice. Immunol Lett. 1994;39:105-111.
56. Levy JE, Jin O, Fujiwara Y, Kuo F, Andrews NC. Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nat Genet. 1999;21:396-399.
57. Tsuchihashi Z, Hansen SL, Quintana L, et al. Transferrin receptor mutation analysis in hereditary hemochromatosis patients. Blood Cells Mol Dis. 1998;24:317-321.
58. Camaschella C, Roetto A, Cali A, et al. The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nat Genet. 2000;25:14-15.
59. Lee PL, Halloran C, West C, Beutler E. Mutation analysis of the transferrin receptor-2 gene in patients with iron overload. Blood Cells Mol Dis. 2001;27:285-289.
60. Aguilar-Martinez P, Esculie-Coste C, Bismuth M, Giansily-Blaizot M, Larrey D, Schved JF. Transferrin receptor-2 gene and non-C282Y homozygous patients with hemochromatosis. Blood Cells Mol Dis. 2001;27:290-293.
61. Barton EH, West PA, Rivers CA, Barton JC, Acton RG. Transferrin receptor-2 (TFR2) mutation Y250X in Alabama Caucasian and African American subjects with and without primary iron overload. Blood Cells Mol Dis. 2001;27:279-284.
62. Hamill RL, Woods JC, Cook BA. Congenital atransferrinemia: a case report and review of the literature. Am J Clin Pathol. 1991;96:215-218.
63. Raja KB, Pountney DJ, Simpson RJ, Peters TJ. Importance of anemia and transferrin levels in the regulation of intestinal iron absorption in hypotransferrinemic mice. Blood. 1999;94:3185-3192.
64. Lee PL, Ho NJ, Olson R, Beutler E. The effect of transferrin polymorphisms on iron metabolism. Blood Cells Mol Dis. 1999;25:374-379.
65. Dennery PA, Spitz DR, Yang G, et al. Oxygen toxicity and iron accumulation in the lungs of mice lacking heme oxygenase-2. J Clin Invest. 1998;101:1001-1011.
66. Okamoto N, Wada S, Oga T, et al. Hereditary ceruloplasmin deficiency with hemosiderosis. Hum Genet. 1996;97:755-758.
67. Lee PL, Gelbart T, West C, Halloran C, MacDonald M, Beutler E. A study of genes that may modulate the expression of hereditary hemochromatosis: transferrin receptor-1, ferritin heavy and light chains, ferroportin, ceruloplasmin, iron responsive binding proteins (IRP)-1 and -2. Blood Cells Mol Dis. In press.
68. Fleming MD, Trenor CC, Su MA, et al. Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat Genet. 1997;16:383-386.
69. Fleming MD, Romano MA, Su MA, Garrick LM, Garrick MD, Andrews NC. Nramp2 is mutated in the anemic belgrade (b) rat: evidence of a role for nramp2 in endosomal iron transport. Proc Natl Acad Sci U S A. 1998;95:1148-1153.
70. Lee PL, Gelbart T, West C, Halloran C, Beutler E. The human nramp2 gene: characterization of the gene structure, alternative splicing, promoter region and polymorphisms. Blood Cells Mol Dis. 1998;24:199-215.
71. Vulpe CD, Kuo YM, Murphy TL, et al. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet. 1999;21:195-199.
72. Kato J, Fujikawa K, Kanda M, et al. A mutation, in the iron-responsive element of H ferritin mRNA, causing autosomal dominant iron overload. Am J Hum Genet. 2001;69:191-197.
73. Rouault T, Klausner R. Regulation of iron metabolism in eukaryotes. Curr Top Cell Regul. 1997;35:1-19.
74. LaVaute T, Smith S, Cooperman S, et al. Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat Genet. 2001;27:209-214.
75. Lee P, Halloran C, Cross AR, Beutler E. NADH-ferric reductase activity associated with dihydropteridine reductase. Biochem Biophys Res Commun. 2000;271:788-795.
76. Donovan A, Brownlie A, Zhou Y, et al. Positional cloning of zebrafish ferroportin 1 identifies a conserved vertebrate iron exporter. Nature. 2000;403:776-781.
77. Umbreit JN, Conrad ME, Moore EG, Latour LF. Iron absorption and cellular transport: the mobilferrin/paraferritin paradigm. Semin Hematol. 1998;35:13-26.
78. Beutler E, West C, Gelbart T. HLA-H and associated proteins in patients with hemochromatosis. Mol Med. 1997;3:397-402.
79. Martinelli I, Mannucci PM, De SV, et al. Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia: a study of 150 families. Blood. 1998;92:2353-2358.
80. Lane DA, Grant PJ. Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease. Blood. 2000;95:1517-1532.
81. Morange PE, Henry M, Tregouet D, et al. The A-844G polymorphism in the PAI-1 gene is associated with a higher risk of venous thrombosis in factor V Leiden carriers. Arterioscler Thromb Vasc Biol. 2000;20:1387-1391.
82. Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet. 1999;353:1167-1173.
83. Simioni P, Sanson BJ, Prandoni P, et al. Incidence of venous thromboembolism in families with inherited thrombophilia. Thromb Haemost. 1999;81:198-202.
84. Rintelen C, Mannhalter C, Ireland H, et al. Oral contraceptives enhance the risk of clinical manifestation of venous thrombosis at a young age in females homozygous for factor V Leiden. Br J Haematol. 1996;93:487-490.
85. Vandenbroucke JP, Koster T, Briet E, Reitsma PH, Bertina RM, Rosendaal FR. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet. 1994;344:1453-1457.