Pathogenesis of hereditary hemochromatosis

Clinics in Liver Disease

Volumn 8, Issue 4, 2004, Pages 755-773

  Fleming, Robert E ^a   Britton, Robert S ^b   Waheed, Abdul ^a   Sly, William S ^a   Bacon, Bruce R ^b  

^a SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b Saint Louis University   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HEPCIDIN; HFE PROTEIN;

CRYPT CELL; DIAGNOSTIC ACCURACY; DNA MODIFICATION; DUODENUM; EXPERIMENTAL MOUSE; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE IDENTIFICATION; GENE MUTATION; GENETIC ANALYSIS; GENETIC ASSOCIATION; HEMOCHROMATOSIS; HEREDITARY HEMOCHROMATOSIS; HOMEOSTASIS; HOMOZYGOTE; HUMAN; HYPOTHESIS; IRON ABSORPTION; IRON METABOLISM; IRON OVERLOAD; IRON TRANSPORT; MOLECULAR CLONING; MUTATIONAL ANALYSIS; NONHUMAN; PATHOGENESIS; POPULATION GENETICS; PROTEIN EXPRESSION; PROTEIN FUNCTION; RETICULOENDOTHELIAL SYSTEM; REVIEW; SMALL INTESTINE ABSORPTION; STATISTICAL SIGNIFICANCE; SYMPTOMATOLOGY;

ANIMALS; ANTIMICROBIAL CATIONIC PEPTIDES; DISEASE MODELS, ANIMAL; DUODENUM; GENETIC PREDISPOSITION TO DISEASE; HEMOCHROMATOSIS; HUMANS; IRON; MICE;

EID: 4744340782     PISSN: 10893261     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cld.2004.06.004     Document Type: Review

References (109)

1. B.R. Bacon, L.W. Powell, P.C. Adams, T.F. Kresina, and J.H. Hoofnagle Molecular medicine and hemochromatosis: at the crossroads Gastroenterology 116 1 1999 193 207
2. E. Beutler, A.V. Hoffbrand, and J.D. Cook Iron deficiency and overload Hematology (Am Soc Hematol Educ Program) 2003 40 61
3. J.N. Feder, A. Gnirke, W. Thomas, Z. Tsuchihashi, D.A. Ruddy, and A. Basava A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis Nat Genet 13 4 1996 399 408
4. M. Simon, M. Bourel, R. Fauchet, and B. Genetet Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis Gut 17 5 1976 332 334
5. B. Mercier, C. Mura, and C. Ferec Putting a hold on 'HLA-H' Nat Genet 15 3 1997 234
6. X.Y. Zhou, S. Tomatsu, R.E. Fleming, S. Parkkila, A. Waheed, and J. Jiang HFE gene knockout produces mouse model of hereditary hemochromatosis Proc Natl Acad Sci USA 95 5 1998 2492 2497
7. S. Bahram, S. Gilfillan, L.C. Kuhn, R. Moret, J.B. Schulze, and A. Lebeau Experimental hemochromatosis due to MHC class I HFE deficiency: immune status and iron metabolism Proc Natl Acad Sci USA 96 23 1999 13312 13317
8. J.E. Levy, L.K. Montross, D.E. Cohen, M.D. Fleming, and N.C. Andrews The C282Y mutation causing hereditary hemochromatosis does not produce a null allele Blood 94 1 1999 9 11
9. J.N. Feder, Z. Tsuchihashi, A. Irrinki, V.K. Lee, F.A. Mapa, and E. Morikang The hemochromatosis founder mutation in HLA-H disrupts beta2-microglobulin interaction and cell surface expression J Biol Chem 272 22 1997 14025 14028
10. A. Waheed, S. Parkkila, X.Y. Zhou, S. Tomatsu, Z. Tsuchihashi, and J.N. Feder Hereditary hemochromatosis: effects of C282Y and H63D mutations on association with beta2-microglobulin, intracellular processing, and cell surface expression of the HFE protein in COS-7 cells Proc Natl Acad Sci USA 94 23 1997 12384 12389
11. S. Parkkila, A.K. Parkkila, A. Waheed, R.S. Britton, X.Y. Zhou, and R.E. Fleming Cell surface expression of HFE protein in epithelial cells, macrophages, and monocytes Haematologica 85 4 2000 340 345
12. M. de Sousa, R. Reimao, R. Lacerda, P. Hugo, S.H. Kaufmann, and G. Porto Iron overload in beta 2-microglobulin-deficient mice Immunol Lett 39 2 1994 105 111
13. M. Santos, M.W. Schilham, L.H. Rademakers, J.J. Marx, M. de Sousa, and H. Clevers Defective iron homeostasis in beta 2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man J Exp Med 184 5 1996 1975 1985
14. J.A. Lebron, M.J. Bennett, D.E. Vaughn, A.J. Chirino, P.M. Snow, and G.A. Mintier Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor Cell 93 1 1998 111 123
15. S. Parkkila, A. Waheed, R.S. Britton, J.N. Feder, Z. Tsuchihashi, and R.C. Schatzman Immunohistochemistry of HLA-H, the protein defective in patients with hereditary hemochromatosis, reveals unique pattern of expression in gastrointestinal tract Proc Natl Acad Sci USA 94 6 1997 2534 2539
16. A. Waheed, S. Parkkila, J. Saarnio, R.E. Fleming, X.Y. Zhou, and S. Tomatsu Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum Proc Natl Acad Sci USA 96 4 1999 1579 1584
17. P. Holmstrom, V. Dzikaite, R. Hultcrantz, O. Melefors, K. Eckes, and P. Stal Structure and liver cell expression pattern of the HFE gene in the rat J Hepatol 39 3 2003 308 314
18. A.S. Zhang, S. Xiong, H. Tsukamoto, and C.A. Enns Localization of iron metabolism-related mRNAs in rat liver indicate that HFE is predominantly expressed in hepatocytes Blood 103 4 2004 1509 1514
19. J.M. Bastin, M. Jones, C.A. O'Callaghan, L. Schimanski, D.Y. Mason, and A.R. Townsend Kupffer cell staining by an HFE-specific monoclonal antibody: implications for hereditary haemochromatosis Br J Haematol 103 4 1998 931 941
20. S. Parkkila, A. Waheed, R.S. Britton, B.R. Bacon, X.Y. Zhou, and S. Tomatsu Association of the transferrin receptor in human placenta with HFE, the protein defective in hereditary hemochromatosis Proc Natl Acad Sci USA 94 24 1997 13198 13202
21. L. Salter-Cid, A. Brunmark, Y. Li, D. Leturcq, P.A. Peterson, and M.R. Jackson Transferrin receptor is negatively modulated by the hemochromatosis protein HFE: implications for cellular iron homeostasis Proc Natl Acad Sci USA 96 10 1999 5434 5439
22. O. Han, J.C. Fleet, and R.J. Wood Reciprocal regulation of HFE and NNamp2 gene expression by iron in human intestinal cells J Nutr 129 1 1999 98 104
23. J.N. Feder, D.M. Penny, A. Irrinki, G.A. Mintier, J.A. Lebron, and C.N. Gross The hereditary hemochromatosis gene and iron homeostasis N.G. Abraham A. Tabillo M. Martelli S. Asano A. Donfrancesco Molecular Biology of Hematopoiesis 6 1999 Kluwer Academic/Plenum Publishers NewYork
24. D.M. Frazer, S.J. Wilkins, E.M. Becker, C.D. Vulpe, A.T. McKie, and D. Trinder Hepcidin expression inversely correlates with the expression of duodenal iron transporters and iron absorption in rats Gastroenterology 123 3 2002 835 844
25. M. Sanchez, R. Queralt, M. Bruguera, J. Rodes, and R. Oliva Cloning, sequencing and characterization of the rat hereditary hemochromatosis promoter: comparison of the human, mouse and rat HFE promoter regions Gene 225 1-2 1998 77 87
26. A. Thenie, M. Orhant, I. Gicquel, P. Fergelot, J.Y. Le Gall, and V. David The HFE gene undergoes alternate splicing processes Blood Cells Mol Dis 26 2 2000 155 162
27. M. Sanchez, M. Bruguera, J. Rodes, and R. Oliva Complete characterization of the 3′ region of the human and mouse hereditary hemochromatosis hfe gene and detection of novel splicing forms Blood Cells Mol Dis 27 1 2001 35 43
28. C.N. Gross, A. Irrinki, J.N. Feder, and C.A. Enns Co-trafficking of HFE, a nonclassical major histocompatibility complex class I protein, with the transferrin receptor implies a role in intracellular iron regulation J Biol Chem 273 34 1998 22068 22074
29. A.M. Giannetti, P.M. Snow, O. Zak, and P.J. Bjorkman Mechanism for multiple ligand recognition by the human transferrin receptor PLoS Biol 1 3 2003 341 350
30. J.A. Lebron, A.P. West Jr, and P.J. Bjorkman The hemochromatosis protein HFE competes with transferrin for binding to the transferrin receptor J Mol Biol 294 1 1999 239 245
31. J.A. Lebron, M.J. Bennett, D.E. Vaughn, A.J. Chirino, P.M. Snow, and G.A. Mintier Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor Cell 93 1 1998 111 123
32. S. Parkkila, O. Niemela, R.S. Britton, R.E. Fleming, A. Waheed, and B.R. Bacon Molecular aspects of iron absorption and HFE expression Gastroenterology 121 6 2001 1489 1496
33. C.N. Roy, D.M. Penny, J.N. Feder, and C.A. Enns The hereditary hemochromatosis protein, HFE, specifically regulates transferrin-mediated iron uptake in HeLa cells J Biol Chem 274 13 1999 9022 9028
34. B. Corsi, S. Levi, A. Cozzi, A. Corti, D. Altimare, and A. Albertini Overexpression of the hereditary hemochromatosis protein, HFE, in HeLa cells induces an iron-deficient phenotype FEBS Lett 460 1 1999 149 152
35. A. Waheed, J.H. Grubb, X.Y. Zhou, S. Tomatsu, R.E. Fleming, and M.E. Costaldi Regulation of transferrin-mediated iron uptake by HFE, the protein defective in hereditary hemochromatosis Proc Natl Acad Sci USA 99 5 2002 3117 3122
36. G. Montosi, P. Paglia, C. Garuti, C.A. Guzman, J.M. Bastin, and M.P. Colombo Wild-type HFE protein normalizes transferrin iron accumulation in macrophages from subjects with hereditary hemochromatosis Blood 96 3 2000 1125 1129
37. L.W. Powell, V.N. Subramaniam, and T.R. Yapp Haemochromatosis in the new millennium J Hepatol 32 1 Suppl 2000 48 62
38. J. Rochette, J.J. Pointon, C.A. Fisher, G. Perera, M. Arambepola, and D.S. Arichchi Multicentric origin of hemochromatosis Gene (HFE) mutations Am J Hum Genet 64 4 1999 1056 1062
39. L.E. Beckman, N. Saha, V. Spitsyn, G. Van Landeghem, and L. Beckman Ethnic differences in the HFE codon 282 (Cys/Tyr) polymorphism Hum Hered 47 5 1997 263 267
40. E. Beutler, V.J. Felitti, J.A. Koziol, N.J. Ho, and T. Gelbart Penetrance of 845G- > A (C282Y) HFE hereditary haemochromatosis mutation in the USA Lancet 359 9302 2002 211 218
41. J.K. Olynyk, D.J. Cullen, S. Aquilia, E. Rossi, L. Summerville, and L.W. Powell A population-based study of the clinical expression of the hemochromatosis gene N Engl J Med 341 10 1999 718 724
42. M.J. Burt, P.M. George, J.D. Upton, J.A. Collett, C.M. Frampton, and T.M. Chapman The significance of haemochromatosis gene mutations in the general population: implications for screening Gut 43 6 1998 830 836
43. S.M. McDonnell, A. Hover, D. Gloe, C.Y. Ou, M.E. Cogswell, and L. Grummer-Strawn Population-based screening for hemochromatosis using phenotypic and DNA testing among employees of health maintenance organizations in Springfield, Missouri Am J Med 107 1 1999 30 37
44. P.C. Adams Nonexpressing homozygotes for C282Y hemochromatosis: minority or majority of cases? Mol Genet Metab 71 1-2 2000 81 86
45. S. Jacolot, G. Le Gac, V. Scotet, I. Quere, C. Mura, and C. Ferec HAMP as a modifier gene that increases the phenotypic expression of the HFE C282Y homozygous genotype Blood 103 7 2004 2835 2840
46. K.K. Steinberg, M.E. Cogswell, J.C. Chang, S.P. Caudill, G.M. McQuillan, and B.A. Bowman Prevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States JAMA 285 17 2001 2216 2222
47. P.A. Gochee, L.W. Powell, D.J. Cullen, S.D. Du, E. Rossi, and J.K. Olynyk A population-based study of the biochemical and clinical expression of the H63D hemochromatosis mutation Gastroenterology 122 3 2002 646 651
48. B.R. Bacon Hemochromatosis: diagnosis and management Gastroenterology 120 3 2001 718 725
49. N. Risch Haemochromatosis, HFE and genetic complexity Nat Genet 17 4 1997 375 376
50. J.J. Pointon, D. Wallace, A.T. Merryweather-Clarke, and K.J. Robson Uncommon mutations and polymorphisms in the hemochromatosis gene Genet Test 4 2 2000 151 161
51. R.S. Britton, R.E. Fleming, S. Parkkila, A. Waheed, W.S. Sly, and B.R. Bacon Pathogenesis of hereditary hemochromatosis: genetics and beyond Semin Gastrointest Dis 13 2 2002 68 79
52. J.E. Levy, L.K. Montross, and N.C. Andrews Genes that modify the hemochromatosis phenotype in mice J Clin Invest 105 9 2000 1209 1216
53. G. Nicolas, N.C. Andrews, A. Kahn, and S. Vaulont Hepcidin, a candidate modifier of the hemochromatosis phenotype in mice Blood 103 7 2004 2841 2843
54. R.E. Fleming, C.C. Holden, S. Tomatsu, A. Waheed, E.M. Brunt, and R.S. Britton Mouse strain differences determine severity of iron accumulation in Hfe knockout model of hereditary hemochromatosis Proc Natl Acad Sci USA 98 5 2001 2707 2711
55. F. Dupic, S. Fruchon, M. Bensaid, O. Loreal, P. Brissot, and N. Borot Duodenal mRNA expression of iron related genes in response to iron loading and iron deficiency in four strains of mice Gut 51 5 2002 648 653
56. F. Dupic, S. Fruchon, M. Bensaid, N. Borot, M. Radosavljevic, and O. Loreal Inactivation of the hemochromatosis gene differentially regulates duodenal expression of iron-related mRNAs between mouse strains Gastroenterology 122 3 2002 745 751
57. N.C. Andrews Disorders of iron metabolism N Engl J Med 341 26 1999 1986 1995
58. A.T. McKie, D. Barrow, G.O. Latunde-Dada, A. Rolfs, G. Sager, and E. Mudaly An iron-regulated ferric reductase associated with the absorption of dietary iron Science 291 5509 2001 1755 1759
59. M.D. Fleming, C.C. Trenor III, M.A. Su, D. Foernzler, D.R. Beier, and W.F. Dietrich Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene Nat Genet 16 4 1997 383 386
60. H. Gunshin, B. Mackenzie, U.V. Berger, Y. Gunshin, M.F. Romero, and W.F. Boron Cloning and characterization of a mammalian proton-coupled metal-ion transporter Nature 388 6641 1997 482 488
61. A. Donovan, A. Brownlie, Y. Zhou, J. Shepard, S.J. Pratt, and J. Moynihan Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter Nature 403 6771 2000 776 781
62. A.T. McKie, P. Marciani, A. Rolfs, K. Brennan, K. Wehr, and D. Barrow A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation Mol Cell 5 2 2000 299 309
63. S. Abboud, and D.J. Haile A novel mammalian iron-regulated protein involved in intracellular iron metabolism J Biol Chem 275 26 2000 19906 19912
64. C.D. Vulpe, Y.M. Kuo, T.L. Murphy, L. Cowley, C. Askwith, and N. Libina Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse Nat Genet 21 2 1999 195 199
65. G.D. McLaren, M.H. Nathanson, A. Jacobs, D. Trevett, and W. Thomson Regulation of intestinal iron absorption and mucosal iron kinetics in hereditary hemochromatosis J Lab Clin Med 117 5 1991 390 401
66. H. Zoller, A. Pietrangelo, W. Vogel, and G. Weiss Duodenal metal-transporter (DMT-1, NRAMP-2) expression in patients with hereditary haemochromatosis Lancet 353 9170 1999 2120 2123
67. H. Zoller, R.O. Koch, I. Theurl, P. Obrist, A. Pietrangelo, and G. Montosi Expression of the duodenal iron transporters divalent-metal transporter 1 and ferroportin 1 in iron deficiency and iron overload Gastroenterology 120 6 2001 1412 1419
68. A. Rolfs, H.L. Bonkovsky, J.G. Kohlroser, K. McNeal, A. Sharma, and U.V. Berger Intestinal expression of genes involved in iron absorption in humans Am J Physiol Gastrointest Liver Physiol 282 4 2002 G598 G607
69. R.E. Fleming, M.C. Migas, X. Zhou, J. Jiang, R.S. Britton, and E.M. Brunt Mechanism of increased iron absorption in murine model of hereditary hemochromatosis: increased duodenal expression of the iron transporter DMT1 Proc Natl Acad Sci USA 96 6 1999 3143 3148
70. K.A. Stuart, G.J. Anderson, D.M. Frazer, L.W. Powell, M. McCullen, and L.M. Fletcher Duodenal expression of iron transport molecules in untreated haemochromatosis subjects Gut 52 7 2003 953 959
71. F. Canonne-Hergaux, J.E. Levy, M.D. Fleming, L.K. Montross, N.C. Andrews, and P. Gros Expression of the DMT1 (NRAMP2/DCT1) iron transporter in mice with genetic iron overload disorders Blood 97 4 2001 1138 1140
72. T. Herrmann, M. Muckenthaler, H.F. Van Der, K. Brennan, S.G. Gehrke, and N. Hubert Iron overload in adult Hfe-deficient mice independent of changes in the steady-state expression of the duodenal iron transporters DMT1 and Ireg1/ferroportin J Mol Med 82 1 2004 39 48
73. R.S. Ajioka, J.E. Levy, N.C. Andrews, and J.P. Kushner Regulation of iron absorption in Hfe mutant mice Blood 100 4 2002 1465 1469
74. H. Kawabata, R. Yang, T. Hirama, P.T. Vuong, S. Kawano, and A.F. Gombart Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family J Biol Chem 274 30 1999 20826 20832
75. R.E. Fleming, M.C. Migas, C.C. Holden, A. Waheed, R.S. Britton, and S. Tomatsu Transferrin receptor 2: continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis Proc Natl Acad Sci USA 97 5 2000 2214 2219
76. H.L. Bonkovsky Iron and the liver Am J Med Sci 301 1 1991 32 43
77. P. Brissot, T.L. Wright, W.L. Ma, and R.A. Weisiger Efficient clearance of non-transferrin-bound iron by rat liver. Implications for hepatic iron loading in iron overload states J Clin Invest 76 4 1985 1463 1470
78. R.G. Batey, P. Lai Chung Fong, S. Shamir, and S. Sherlock A non-transferrin-bound serum iron in idiopathic hemochromatosis Dig Dis Sci 25 5 1980 340 346
79. A. Deiss Iron metabolism in reticuloendothelial cells Semin Hematol 20 2 1983 81 90
80. G.D. McLaren Reticuloendothelial iron stores and hereditary hemochromatosis: a paradox J Lab Clin Med 113 2 1989 137 138
81. E. Moura, M.A. Noordermeer, N. Verhoeven, A.F. Verheul, and J.J. Marx Iron release from human monocytes after erythrophagocytosis in vitro: an investigation in normal subjects and hereditary hemochromatosis patients Blood 92 7 1998 2511 2519
82. C. Finch Regulators of iron balance in humans Blood 84 6 1994 1697 1702
83. C. Pigeon, G. Ilyin, B. Courselaud, P. Leroyer, B. Turlin, and P. Brissot A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload J Biol Chem 276 11 2001 7811 7819
84. A. Krause, S. Neitz, H.J. Magert, A. Schulz, W.G. Forssmann, and P. Schulz-Knappe LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity FEBS Lett 480 2-3 2000 147 150
85. C.H. Park, E.V. Valore, A.J. Waring, and T. Ganz Hepcidin, a urinary antimicrobial peptide synthesized in the liver J Biol Chem 276 11 2001 7806 7810
86. T. Ganz Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation Blood 102 3 2003 783 788
87. G. Nicolas, L. Viatte, M. Bennoun, C. Beaumont, A. Kahn, and S. Vaulont Hepcidin, a new iron regulatory peptide Blood Cells Mol Dis 29 3 2002 327 335
88. G. Nicolas, M. Bennoun, I. Devaux, C. Beaumont, B. Grandchamp, and A. Kahn Lack of hepcidin gene expression and severe tissue iron overload in Upstream Stimulator Factor 2 (USF2) knockout mice Proc Natl Acad Sci USA 98 15 2001 8780 8785
89. E. Nemeth, E.V. Valore, M. Territo, G. Schiller, A. Lichtenstein, and T. Ganz Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein Blood 101 7 2002 2461 2463
90. R.E. Fleming, and W.S. Sly Hepcidin: a putative iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia of chronic disease Proc Natl Acad Sci USA 98 15 2001 8160 8162
91. D.A. Weinstein, C.N. Roy, M.D. Fleming, M.F. Loda, J.I. Wolfsdorf, and N.C. Andrews Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease Blood 100 10 2002 3776 3781
92. K.R. Bridle, D.M. Frazer, S.J. Wilkins, J.L. Dixon, D.M. Purdie, and D.H. Crawford Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis Lancet 361 9358 2003 669 673
93. K.A. Ahmad, J.R. Ahmann, M.C. Migas, A. Waheed, R.S. Britton, and B.R. Bacon Decreased liver hepcidin expression in the hfe knockout mouse Blood Cells Mol Dis 29 3 2002 361 366
94. M. Muckenthaler, C.N. Roy, A.O. Custodio, B. Minana, J. deGraaf, and L.K. Montross Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosis Nat Genet 34 1 2003 102 107
95. A. Roetto, G. Papanikolaou, M. Politou, F. Alberti, D. Girelli, and J. Christakis Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis Nat Genet 33 1 2003 21 22
96. A.P. West Jr, M.J. Bennett, V.M. Sellers, N.C. Andrews, C.A. Enns, and P.J. Bjorkman Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE J Biol Chem 275 49 2000 38135 38138
97. C. Camaschella, A. Roetto, A. Cali, M. De Gobbi, G. Garozzo, and M. Carella The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22 Nat Genet 25 1 2000 14 15
98. R.E. Fleming, J.R. Ahmann, M.C. Migas, A. Waheed, H.P. Koeffler, and H. Kawabata Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochromatosis Proc Natl Acad Sci USA 99 16 2002 10653 10658
99. G.J. Anderson Control of iron absorption J Gastroenterol Hepatol 11 11 1996 1030 1032
100. D. Trinder, J.K. Olynyk, W.S. Sly, and E.H. Morgan Iron uptake from plasma transferrin by the duodenum is impaired in the Hfe knockout mouse Proc Natl Acad Sci USA 99 8 2002 5622 5626
101. D.M. Frazer, and G.J. Anderson The orchestration of body iron intake: how and where do enterocytes receive their cues? Blood Cells Mol Dis 30 3 2003 288 297
102. A. Pietrangelo Non-HFE hemochromatosis Hepatology 39 1 2004 21 29
103. A. Roetto, A. Totaro, A. Piperno, A. Piga, F. Longo, and G. Garozzo New mutations inactivating transferrin receptor 2 in hemochromatosis type 3 Blood 97 9 2001 2555 2560
104. O.T. Njajou, N. Vaessen, M. Joosse, B. Berghuis, J.W. van Dongen, and M.H. Breuning A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis Nat Genet 28 3 2001 213 214
105. G. Montosi, A. Donovan, A. Totaro, C. Garuti, E. Pignatti, and S. Cassanelli Autosomal dominant hemochromatosis is associated with a mutation in the ferroportin (SCL11A3) gene J Clin Invest 108 4 2001 619 623
106. G. Papanikolaou, M.E. Samuels, E.H. Ludwig, M.L. MacDonald, P.L. Franchini, and M.P. Dube Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis Nat Genet 36 1 2004 77 82
107. V.R. Gordeuk African iron overload Semin Hematol 39 4 2002 263 269
108. V.R. Gordeuk, A. Caleffi, E. Corradini, F. Ferrara, R.A. Jones, and O. Castro Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene Blood Cells Mol Dis 31 3 2003 299 304
109. J.C. Barton, R.T. Acton, C.A. Rivers, L.F. Bertoli, T. Gelbart, and C. West Genotypic and phenotypic heterogeneity of African Americans with primary iron overload Blood Cells Mol Dis 31 3 2003 310 319