Molecular basis of hereditary hemochromatosis;Molekularne podstawy dziedzicznej hemochromatozy

Postepy Higieny i Medycyny Doswiadczalnej

Volumn 60, Issue , 2006, Pages 217-226

  Romanowski, Tomasz ^a   Sikorska, Katarzyna ^b   Bielawski, Krzysztof Piotr ^a  

^a UNIVERSITY OF GDA SK   (Poland)

^b MEDICAL UNIVERSITY OF GDANSK   (Poland)

Author keywords

HAMP; Hemochromatosis; HFE; HJV; Iron; SLC40A1; TFR2

Indexed keywords

ANTIMICROBIAL CATIONIC PEPTIDE; CATION TRANSPORT PROTEIN; HEPCIDIN; HFE PROTEIN, HUMAN; HLA ANTIGEN CLASS 1; IRON; MEMBRANE PROTEIN; METAL TRANSPORTING PROTEIN 1; TFR2 PROTEIN, HUMAN; TRANSFERRIN RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL; GENETICS; HEMOCHROMATOSIS; HUMAN; METABOLISM; MUTATION; REVIEW;

ANIMALS; ANTIMICROBIAL CATIONIC PEPTIDES; CATION TRANSPORT PROTEINS; ENGLISH ABSTRACT; HEMOCHROMATOSIS; HISTOCOMPATIBILITY ANTIGENS CLASS I; HUMANS; IRON; MEMBRANE PROTEINS; MUTATION; RECEPTORS, TRANSFERRIN;

EID: 33846068273     PISSN: 00325449     EISSN: 17322693     Source Type: Journal    
DOI: None     Document Type: Review

References (116)

1. Abboud S., Haile D.J.: A novel mammalian ironregulated protein involved in intracellular iron metabolism. J. Biol. Chem., 2000; 275: 19906-19912
2. Anderson G.J., Powell L.W.: HFE and non-HFE hemochromatosis. Int. J. Hematol., 2002; 76: 203-207
3. Andrews N.C.: Disorders of iron metabolism. N. Engl. J. Med., 1999; 341: 1986-1995
4. Arden K.E., Wallace D.F., Dixon J.L., Summerville L., Searle J.W., Anderson G.J., Ramm G.A., Powell L.W., Subramaniam V.N.: A novel mutation in ferroportin1 is associated with haemochromatosis in a Solomon Islands patient. Gut, 2003; 52: 1215-1217
5. Bacon B.R.: Hemochromatosis: diagnosis and management. Gastroenterology, 2001; 120: 718-725
6. Barton J.C., Sawada-Hirai R., Rothenberg B.E., Acton R.T.: Two novel missense mutations in the HFE gene (I105T and G93R) and identifi-cation of the S65C mutation in Alabama hemochromatosis probands. Blood. Cell. Mol. Dis., 1999; 25: 147-155
7. Bennett M.J., Lebron J.A., Bjorkman P.J.: Crystal structure of the haemochromatosis protein HFE complexed with transferrin receptor. Nature, 2000; 403: 46-53
8. Beutler E., Griffin M.J., Gelbart T., West C.: A previously undescribed nonsense mutation of the HFE gene. Clin. Genet., 2002; 61: 40-42
9. Biasiotto G., Belloli S., Ruggeri G., Zanella I., Gerardi G., Corrado M., Gobbi E., Albertini A., Arosio P.: Identification of new mutations of the HFE, hepcidin, and transferrin receptor 2 genes by denaturing HPLC analysis of individuals with biochemical indications of iron overload. Clin. Chem., 2003; 49: 1981-1988
10. Biasiotto G., Roetto A., Daraio F., Polotti A., Gerardi G.M., Girelli D., Cremonesi L., Arosio P., Camaschella C.: Identification of new mutations of hepcidin and hemojuvelin in patients with HFE C282Y allele. Blood Cells Mol. Dis., 2004; 33: 338-343
11. Boldt D.H.: New perspectives on iron: an introduction. Am. J. Med. Sci., 1999; 318: 207-212
12. Bomford A.: Genetics of haemochromatosis. Lancet, 2002; 360: 1673-1681
13. Bothwell T.H., McPhail A.P.: Hereditary haemochromatosis: etiologic, pathologic and clinical aspects. Semin. Hematol., 1998; 35: 55-71
14. Bottomley S.S., May B.K., Cox T.C., Cotter P.D., Bishop D.F.: Molecular defects of erythroid 5-aminolevulinate synthase in X-linked sideroblastic anemia. J. Bioenerg. Biomembr., 1995; 27: 161-168
15. Bradbury R., Fagan E., Payne S.J.: Two novel polymorphisms (E277K and V212V) in the haemochromatosis gene HFE. Hum. Mutat., 2000; 15: 120
16. Bridle K.R., Frazer D.M., Wilkins S.J., Dixon J.L., Purdie D.M., Crawford D.H.G., Subramaniam V.N., Powell L.W., Anderson G.J., Ramm G.A.: Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homeostasis. Lancet, 2003; 361: 669-673
17. Camaschella C., Roetto A., Cali A., De Gobbi M., Garozzo G., Carella M., Majorano N., Totaro A., Gasparini P.: The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nat. Genet., 2000; 25: 14-15.
18. Camaschella C., Roetto A., De Gobbi M.: Genetic haemochromatosis: genes and mutations associated with iron loading. Best. Pract. Res. Clin. Haematol., 2002; 15: 261-276
19. Carella M., D'Ambrosio L., Totaro A., Grifa A., Valentino M.A., Piperno A., Girelli D., Roetto A., Franco B., Gasparini P., Camaschella C.: Mutation analysis of the HLA-H gene in Italian hemochromatosis patients. Am. J. Hum. Genet., 1997; 60: 828-832
20. Cazzola M.: Genetic disorders of iron overload and the novel 'ferroportin disease'. Haematologica, 2003; 88: 721-724
21. Cazzola M., Cremonesi L., Papaioannou M., Soriani N., Kioumi A., Charalambidou A., Paroni R., Romtsou K., Levi S., Ferrari M., Arosio P., Christakis J.: Genetic hyperferritinaemia and reticuloendothelial iron overload associated with a three base pair deletion in the coding region of the ferroportin gene (SLC11A3). Br. J. Haematol., 2002; 119: 539-546
22. Conrad M.E., Umbreit J.N., Moore E.G.: Iron absorption and transport. Am. J. Med. Sci., 1999; 318: 213-229
23. Daniele B., D'Agostino L.: Proliferation and differentiation of the small intestinal epithelium: from petri dish to bedside. Ital. J. Gastroenterol., 1994; 26: 459-470
24. Daraio F., Ryan E., Gleeson F., Roetto A., Crowe J., Camaschella C.: Juvenile hemochromatosis due to G320V/Q116X compound heterozygosity of hemojuvelin in an Irish patient. Blood Cells Mol. Dis., 2005; 35: 174-176
25. Delatycki M.B., Allen K.J., Gow P., MacFarlane J., Radomski C., Thompson J., Hayden M.R., Goldberg Y.P., Samuels M.E.: A homozygous HAMP mutation in a multiply consanguineous family with pseudodominant juvenile hemochromatosis. Clin. Genet., 2004; 65: 378-383
26. Devalia V., Carter K., Walker A.P., Perkins S.J., Worwood M., May A., Dooley J.S.: Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3). Blood, 2002; 100: 695-697
27. de Villiers J.N.P., Hillermann R., Loubser L., Kotze M.J.: Spectrum of mutations in the HFE gene implicated in haemochromatosis and porphyria. Hum. Mol. Genet., 1999; 8: 1517-1522
28. Donovan A., Brownlie A., Zhou Y., Shepard J., Pratt S.J., Moynihan J., Paw B.H., Drejer A., Barut B., Zapata A., Law T.C., Brugnara C., Lux S.E., Pinkus G.S., Pinkus J.L., Kingsley P.D., Palis J., Fleming M.D., Andrews N.C., Zon L.I.: Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature, 2000; 403: 776-781
29. Drakesmith H., Schimanski L.M., Ormerod E., Merryweather-Clarke A.T., Viprakasit V., Edwards J.P., Sweetland E., Bastin J.M., Cowley D., Chinthammitr Y., Robson K.J., Townsend A.R.: Resistance to hepcidin is conferred by hemochromatosis-associated mutations of ferroportin. Blood, 2005; 106: 1092-1097
30. Ehrlich R., Lemonnier F.A.: HFE: A novel nonclassical class I molecule that is involved in iron metabolism. Immunity, 2000; 13: 585-588
31. Feder J.N., Gnirke A., Thomas W., Tsuchihashi Z., Ruddy D.A., Basava A., Dormishian F., Domingo R.Jr, Ellis M.C., Fullan A., Hinton L.M., Jones N.L., Kimmel B.E., Kronmal G.S., Lauer P., Lee V.K., Loeb D.B., Mapa F.A., McClelland E., Meyer N.C., Mintier G.A., Moeller N., Moore T., Morikang E., Prass C.E., Quintana L., Starnes S.M., Schatzman R.C., Brunke K.J., Drayna D.T., Risch N.J., Bacon B.R., Wolff R.K.: A novel MHC class I-like gene is mutated in patients with hereditary hemochromatosis. Nat. Genet., 1996; 13: 399-408
32. Fleming R.E., Ahmann J.R., Migas M.C., Waheed A., Koeffler H.P., Kawabata H., Britton R.S., Bacon B.R., Sly W.S.: Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochromatosis. Proc. Natl. Acad. Sci. USA, 2002; 99: 10653-10658
33. Ganz T.: Hepcidin-A regulator of intestinal iron absorption and iron recycling by macrophages. Best. Pract. Res. Clin. Haematol., 2005; 18: 171-182
34. Gehrke S.G., Pietrangelo A., Kascak M., Braner A., Eisold M., Kulaksiz H., Herrmann T., Hebling U., Bents K., Gugler R., Stremmel W.: HJV gene mutations in European patients with juvenile hemochromatosis. Clin. Genet., 2005; 67: 425-428
35. Gerlach M., Ben-Shachar D., Riederer P., Youdim M.B.: Altered brain metabolism of iron as a cause of neurodegenerative diseases? J. Neurochem., 1994; 63: 793-807
36. Girelli D., Bozzini C., Roetto A., Alberti F., Daraio F., Colombari R., Olivieri O., Corrocher R., Camaschella C.: Clinical and pathologic findings in hemochromatosis type 3 due to a novel mutation in transferrin receptor 2 gene. Gastroenterology, 2002; 122: 1295-1302
37. Gordeuk V.R., CaleffiA., Corradini E., Ferrara F., Jones R.A., Castro O., Onyekwere O., Kittles R., Pignatti E., Montosi G., Garuti C., Gangaidzo I.T., Gomo Z.A., Moyo V.M., Rouault T.A., MacPhail P., Pietrangelo A.: Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene. Blood Cells Mol. Dis., 2003; 31: 299-304
38. Griffiths W.J., Cox T.M.: Co-localization of the mammalian hemochromatosis gene product (HFE) and a newly identified transferrin receptor (TfR2) in intestinal tissue and cells. J. Histochem. Cytochem., 2003; 51: 613-624
39. Gunshin H., Mackenzie B., Berger U.V., Gunshin Y., Romero M.F., Boron W.F., Nussberger S., Gollan J.L., Hediger M.A.: Cloning and characterization of a mammalian protoncoupled metal-ion transporter. Nature, 1997; 388: 482-488
40. Halliwell B., Gutteridge J.M.: Biologically relevant metal ion-dependent hydroxyl radical generation. An update. FEBS Lett., 1992; 307: 108-112
41. Hanson E.H., Imperatore G., Burke W.: HFE gene and hereditary hemochromatosis: A HuGE review. Am. J. Epidemiol., 2001; 154: 193-206
42. Hattori A., Wakusawa S., Hayashi H., Harashima A., Sanae F., Kawanaka M., Yamada G., Yano M., Yoshioka K.: AVAQ 594-597 deletion of the TFR2 gene in a Japanese family with hemochromatosis. Hepatol. Res., 2003; 26: 154-156
43. Hetet G., Devaux I., Soufir N., Grandchamp B., Beaumont C.: Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations. Blood, 2003; 102: 1904-1910
44. Hocker M., Weidenmann B.: Molecular mechanisms of enteroendocrine differentiation. Ann. N.Y. Acad. Sci., 1998; 859: 160-174
45. Hofmann W.K., Tong X.J., Ajioka R.S., Kushner J.P., Koeffler H.P.: Mutation analysis of transferrin-receptor 2 in patients with atypical hemochromatosis. Blood, 2002; 100: 1099-1100
46. Huang F.W., Rubio-Aliaga I., Kushner J.P., Andrews N.C., Fleming M.D.: Identification of a novel mutation (C321X) in HJV. Blood, 2004; 104: 2176-2177
47. Huebers H.A., Csiba E., Huebers E., Finch C.A.: Competitive advantage of diferric transferrin in delivering iron to reticulocytes. Proc. Natl. Acad. Sci. USA, 1983; 80: 300-304
48. Imanishi H., Liu W., Cheng J., Ikeda N., Amuro Y., Hada T.: Idiopathic hemochromatosis with the mutation of Ala176Val heterozygous for HFE gene. Intern. Med., 2001; 40: 479-483
49. Jacolot S., Le Gac G., Scotet V., Quere I., Mura C., Ferec C.: HAMP as a modifier gene that increases the phenotypic expression of the HFE pC282Y homozygous genotype. Blood, 2004; 103: 2835-2840
50. Janosi A., Andrikovics H., Vas K., Bors A., Hubay M., Sapi Z., Tordai A.: Homozygosity for a novel nonsense mutation (G66X) of the HJV gene causes severe juvenile hemochromatosis with fatal cardiomyopathy. Blood, 2005; 105: 432
51. Jones D.C., Young N.T., Pigott C., Fuggle S.V., Barnardo M.C., Marshall S.E., Bunce M.: Comprehensive hereditary hemochromatosis genotyping. Tissue Antigens, 2002; 60: 481-488
52. Jouanolle A.M., Douabin-Gicquel V., Halimi C., Loreal O., Fergelot P., Delacour T., de Lajarte-Thirouard A.S., Turlin B., Le Gall J.Y., Cadet E., Rochette J., David V., Brissot P.: Novel mutation in ferroportin 1 gene is associated with autosomal dominant iron overload. J. Hepatol., 2003; 39: 286-289
53. Kato J., Fujikawa K., Kanda M., Fukuda N., Sasaki K., Takayama T., Kobune M., Takada K., Takimoto R., Hamada H., Ikeda T., Niitsu Y.: A mutation, in the iron-responsive element of H ferritin mRNA, causing autosomal dominant iron overload. Am. J. Hum. Genet., 2001; 69: 191-197
54. Kawabata H., Yang R., Hirama T., Vuong P.T., Kawano S., Gombart A.F., Koeffler H.P.: Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family. J. Biol. Chem., 1999; 274: 20826-20832
55. Kelly A.L., Lunt P.W., Rodrigues F., Berry P.J., Flynn D.M., McKiernan P.J., Kelly D.A., Mieli-Vergani G., Cox T.M.: Classification and genetic features of neonatal haemochromatosis: A study of 27 affected pedigrees and molecular analysis of genes implicated in iron metabolism. J. Med. Genet., 2001; 38: 599-610
56. Koyama C., Wakusawa S., Hayashi H., Suzuki R., Yano M., Yoshioka K., Kozuru M., Takayamam Y., Okada T., Mabuchi H.: Two novel mutations, L490R and V561X, of the transferrin receptor 2 gene in Japanese patients with hemochromatosis. Haematologica, 2005; 90: 302-307
57. Koyama C., Wakusawa S., Hayashi H., Ueno T., Suzuki R., Yano M., Saito H., Okazaki T.: A Japanese family with ferroportin disease caused by a novel mutation of SLC40A1 gene: hyperferritinemia associated with a relatively low transferrin saturation of iron. Intern. Med., 2005; 44: 990-993
58. Krause A., Neitz S., Magert H.J., Schulz A., Forssmann W.G., Schulz-Knappe P., Adermann K.: LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett., 2000; 480: 147-150
59. Lanzara C., Roetto A., Daraio F., Rivard S.R., Ficarella R., Simard H., Cox T.M., Cazzola M., Piperno A., Gimenez-Roqueplo A-P., Grammatico P., Volinia S., Gasparini P., Camaschella C.: The spectrum of hemojuvelin gene mutation in 1q-linked juvenile hemochromatosis. Blood, 2004; 103: 4317-4321
60. Lee P.L., Barton J.C., Brandhagen D., Beutler E.: Hemojuvelin (HJV) mutations in persons of European, African-American and Asian ancestry with adult onset haemochromatosis. Br. J. Haematol., 2004; 127: 224-229
61. Lee P.L., Beutler E., Rao S.V., Barton J.C.: Genetic abnormalities and juvenile hemochromatosis: mutations of the HJV gene encoding hemojuvelin. Blood, 2004; 103: 4669-4671
62. Le Gac G., Dupradeau F.Y., Mura C., Jacalot S., Scotet V., Esnault G., Mercier A.Y., Rochette J., Ferec C.: Phenotypic expression of the C282Y/Q283P compound heterozygosity in HFE and molecular modeling of the Q283P mutation effect. Blood. Cell. Mol. Dis., 2003; 30: 231-237
63. Le Gac G., Mons F., Jacolot S., Scotet V., Ferec C., Frebourg T.: Early onset hereditary hemochromatosis resulting from a novel TFR2 gene nonsense mutation (R105X) in two siblings of north French descent. Br. J. Haematol., 2004; 125: 674-678
64. Lieu P.T., Heiskala M., Peterson P.A., Yang Y.: The roles of iron in health and disease. Mol. Aspects. Med., 2001; 22: 1-87
65. Lou D.Q., Lesbordes J.C., Nicolas G., Viatte L., Bennoun M., Van Rooijen N., Kahn A., Renia L., Vaulont S.: Iron-and inflammationinduced hepcidin gene expression in mice is not mediated by Kupffer cells in vivo. Hepatology, 2005; 41: 1056-1064
66. Majore S., Binni F., Pennese A., De Santis A., Crisi A., Grammatico P.: HAMP gene mutation c.208T>C (p.C70R) identified in an Italian patient with severe hereditary hemochromatosis. Hum. Mutat., 2004; 23: 400
67. Matthes T., Aguilar-Martinez P., Pizzi-Bosman L., Darbellay R., Rubbia-Brandt L., Giostra E., Michel M., Ganz T., Beris P.: Severe hemochromatosis in a Portuguese family associated with a new mutation in the 5'-UTR of the HAMP gene. Blood, 2004; 104: 2181-2183
68. Mattman A., Huntsman D., Lockitch G., Langlois S., Buskard N., Ralston D., Butterfield Y., Rodrigues P., Jones S., Porto G., Marra M., De Sousa M., Vatcher G.: Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: identification of a novel TfR2 mutation. Blood, 2002; 100: 1075-1077
69. May B.K., Dogra S.C., Sadlon T.J., Bhasker C.R., Cox T.C., Bottomley S.S.: Molecular regulation of heme biosynthesis in higher vertebrates. Prog. Nucleic. Acid. Res. Mol. Biol., 1995; 51: 1-51
70. McCord J.M.: Iron, free radicals, and oxidative injury. Semin. Hematol., 1998; 35: 5-12
71. McKie A.T., Barrow D., Latunde-Dada G.O., Rolfs A., Sager G., Mudaly E., Mudaly M., Richardson C., Barlow D., Bomford A., Peters T.J., Raja K.B., Shirali S., Hediger M.A., Farzaneh F., Simpson R.J.: An iron-regulated ferric reductase associated with the absorption of dietary iron. Science, 2001; 291: 1755-1759
72. McKie A.T., Marciani P., Rolfs A., Brennan K., Wehr K., Barrow D., Miret S., Bomford A., Peters T.J., Farzaneh F., Hediger M.A., Hentze M.W., Simpson R.J.: A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol. Cell., 2000; 5: 299-309
73. Merryweather-Clarke A.T., Cadet E., Bomford A., Capron D., Viprakasit V., Miller A., McHugh P.J., Chapman R.W., Pointon J.J., Wimhurst V.L., Livesey K.J., Tanphaichitr V., Rochette J., Robson K.J.: Digenic inheritance of mutations in HAMP and HFE results in different types of haemochromatosis. Hum. Mol. Genet., 2003; 12: 2241-2247
74. Montosi G., Donovan A., Totaro A., Garuti C., Pignatti E., Cassanelli S., Trenor C.C., Gasparini P., Andrews N.C., Pietrangelo A.: Autosomaldominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. J. Clin. Invest., 2001; 108: 619-623
75. Mura C., Raguenes O., Ferec C.: HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis. Blood, 1999; 93: 2502-2505
76. Nemeth E., Tuttle M.S., Powelson J., Vaughn M.B., Donovan A., Ward D.M., Ganz T., Kaplan J.: Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science, 2004; 306: 2090-2093
77. Nemeth E., Valore E.V., Territo M., Schiller G., Lichtenstein A., Ganz T.: Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood, 2003; 101: 2461-2463
78. Nicolas G., Bennoun M., Devaux I., Beaumont C., Grandchamp B., Kahn A., Vaulont S.: Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc. Natl. Acad. Sci. USA, 2001; 98: 8780-8785
79. Nicolas G., Bennoun M., Porteu A., Mativet S., Beaumont C., Grandchamp B., Sirito M., Sawadogo M., Kahn A., Vaulont S.: Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc. Natl. Acad. Sci. USA, 2002; 99: 4596-4601
80. Nicolas G., Chauvet C., Viatte L., Danan J.L., Bigard X., Devaux I., Beaumont C., Kahn A., Vaulont S.: The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J. Clin. Invest., 2002; 110: 1037-1044
81. Nicolas G., Viatte L., Lou D.Q., Bennoun M., Beaumont C., Kahn A., Andrews N.C., Vaulont S.: Constitutive hepcidin expression prevents iron overload in a mouse model of hemochromatosis. Nat. Genet., 2003; 34: 97-101
82. Njajou O.T., Vaessen N., Joosse M., Berghuis B., van Dongen J.W., Breuning M.H., Snijders P.J., Rutten W.P., Sandkuijl L.A., Oostra B.A., van Duijn C.M., Heutink P.: A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis. Nat. Genet., 2001; 28: 213-214
83. Oberkanins C., Moritz A., de Villiers J.N., Kotze M.J., Kury F.: A reverse-hybridization assay for the rapid and simultaneous detection of nine HFE gene mutations. Genet. Test., 2000; 4: 121-124
84. Papanikolaou G., Samuels M.E., Ludwig E.H., MacDonald M.L., Franchini P.L., Dube M.P., Andres L., MacFarlane J., Sakellaropoulos N., Politou M., Nemeth E., Thompson J., Risler J.K., Zaborowska C., Babakaiff R., Radomski C.C., Pape T.D., Davidas O., Christakis J., Brissot P., Lockitch G., Ganz T., Hayden M.R., Goldberg Y.P.: Mutations in HFE2 cause iron overload in chromosome 1qlinked juvenile hemochromatosis. Nat. Genet., 2004; 36: 77-82
85. Park C.H., Valore E.V., Waring A.J., Ganz T.: Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J. Biol. Chem., 2001; 276: 7806-7810
86. Pietrangelo A.: The ferroportin disease. Blood. Cells. Mol. Dis., 2004; 32: 131-138
87. Pietrangelo A., CaleffiA., Henrion J., Ferrara F., Corradini E., Kulaksiz H., Stremmel W., Andreone P., Garuti C.: Juvenile hemochromatosis associated with pathogenic mutations of adult hemochromatosis genes. Gastroenterology, 2005; 128: 470-479
88. Pietrangelo A., Montosi G., Totaro A., Garuti C., Conte D., Cassanelli S., Fraquelli M., Sardini C., Vasta F., Gasparini P.: Hereditary hemochromatosis in adults without pathogenic mutations in the hemochromatosis gene. N. Engl. J. Med., 1999; 341: 725-732
89. Pigeon C., Ilyin G., Courselaud B., Leroyer P., Turlin B., Brissot P., Loreal O.: A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J. Biol. Chem., 2001; 276: 7811-7819
90. Piperno A., Arosio C., Fossati L., Vigano M., Trombini P., Vergani A., Mancia G.: Two novel nonsense mutations of HFE gene in five unrelated italian patients with hemochromatosis. Gastroenterology, 2000; 119: 441-445
91. Pointon J.J., Wallace D., Merryweather-Clarke A.T., Robson K.J.: Uncommon mutations and polymorphisms in the hemochromatosis gene. Genet. Test., 2000; 4: 151-161
92. Ponka P.: Iron metabolism: Physiology and pathophysiology. Trace. Elem. Res. Hum., 1999; 5: 55-57
93. Roetto A., Daraio F., Porporato P., Caruso R., Cox T.M., Cazzola M., Gasparini P., Piperno A., Camaschella C.: Screening hepcidin for mutations in juvenile hemochromatosis: identification of a new mutation (C70R). Blood, 2004; 103: 2407-2409
94. Roetto A., Merryweather-Clarke A.T., Daraio F., Livesey K., Pointon J.J., Barbabietola G., Piga A., Mackie P.H., Robson K.J., Camaschella C.: A valine deletion of ferroportin 1: A common mutation in hemochromastosis type 4. Blood, 2002; 100: 733-734
95. Roetto A., Papanikolau G., Politou M., Alberti F., Gitrelli D., Christakis J., Loukopoulos D., Camaschella C.: Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat. Genet., 2003; 33: 21-22
96. Roetto A., Totaro A., Piperno A., Piga A., Longo F., Garozzo G., Cali A., De Gobbi M., Gasparini P., Camaschella C.: New mutations inactivating ransferrin receptor 2 in hemochromatosis type 3. Blood, 2001; 97: 2555-2560
97. Rosmorduc O., Poupon R., Nion I., Wendum D., Feder J., Béréziat G., Hermelin B.: Differential HFE allele expression in hemochromatosis heterozygotes. Gastroenterology, 2000; 119: 1075-1086
98. Roy C.N., Enns C.A.: Iron homeostasis: new tales from the crypt. Blood, 2000; 96: 4020-4027
99. Schimanski L.M., Drakesmith H., Merryweather-Clarke A.T., Viprakasit V., Edwards J.P., Sweetland E., Bastin J.M., Cowley D., Chinthammitr Y., Robson K.J., Townsend A.R.: In vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations. Blood, 2005; 105: 4096-4102
100. Sham R.L., Phatak P.D., West C., Lee P., Andrews C., Beutler E.: Autosomal dominant hereditary hemochromatosis associated with a novel ferroportin mutation and unique clinical features. Blood Cells Mol. Dis., 2005; 34: 157-161
101. Sheldon J.H.: Haemochromatosis. Oxford University Press, 1935
102. Simon M., Bourel M., Fauchet R., Genetet B.: Association of HLAA3 and HLA-B14 antigens with idiopathic haemochromatosis. Gut, 1976; 17: 332-334
103. Touret N., Furuya W., Forbes J., Gros P., Grinstein S.: Dynamic traffic through the recycling compartment couples the metal transporter Nramp2 (DMT1) with the transferrin receptor. J. Biol. Chem., 2003; 278: 25548-25557
104. Trinder D., Olynyk J.K., Sly W.S., Morgan E.H.: Iron uptake from plasma transferrin by the duodenum is impaired in the HFE knockout mouse. Proc. Natl. Acad. Sci. USA, 2002; 99: 5622-5626
105. Vulpe C.D., Kuo Y.M., Murphy T.L., Cowley L., Askwith C., Libina N., Gitschier J., Anderson G.J.: Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat. Genet., 1999; 21: 195-199
106. Waheed A., Grubb J.H., Zhou X.Y., Tomatsu S., Fleming R.E., Costaldi M.E., Britton R.S., Bacon B.R., Sly W.S.: Regulation of transferrinmediated iron uptake by HFE, the protein defective in hereditary hemochromatosis. Proc. Natl. Acad. Sci. USA, 2002; 99: 3117-3122
107. Waheed A., Parkkila S., Zhou X.Y., Tomatsu S., Tsuchihashi Z., Feder J.N., Schatzman R.C., Britton R.S., Bacon B.R., Sly W.S.: Hereditary haemochromatosis: effects of the C282Y and H63D mutations on association with b2-microglobulin, intracellular processing, and cell surface expression of the HFE protein in COS-7cells. Proc. Natl. Acad. Sci. USA, 1997; 94: 12384-12389
108. Wallace D.F., Pedersen P., Dixon J.L., Stephenson P., Searle J.W., Powell L.W., Subramaniam V.N.: Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis. Blood, 2002; 100: 692-694
109. Wallace D.F., Summerville L., Lusby P.E., Subramaniam V.N.: First phenotypic description of transferrin receptor 2 knockout mouse, and the role of hepcidin. Gut, 2005; 54: 980-986
110. Wessling-Resnick M.: Biochemistry of iron uptake. Crit. Rev. Biochem. Mol. Biol., 1999; 34: 285-314
111. West A.P.Jr, Bennett M.J., Sellers V.M., Andrews N.C., Enns C.A., Bjorkman P.J.: Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE. J. Biol. Chem., 2000; 275: 38135-38138
112. Wigg A.J., Harley H., Casey G.: Heterozygous recipient and donor HFE mutations associated with a hereditary haemochromatosis phenotype after liver transplantation. Gut, 2003; 52: 433-435
113. Yip R.: Iron deficiency. Bull. World Health Organ., 1998; 76(Suppl.2): 121-123
114. Yoshida K., Furihata K., Takeda S., Nakamura A., Yamamoto K., Morita H., Hiyamuta S., Ikeda S., Shimizu N., Yanagisawa N.: A mutation in the ceruloplasmin gene is associated with systemic hemosiderosis in humans. Nat. Genet., 1995; 9: 267-272
115. Zaahl M.G., Merryweather-Clarke A.T., Kotze M.J., van der Merwe S., Warnich L., Robson K.J.: Analysis of genes implicated in iron regulation in individuals presenting with primary iron overload. Hum. Genet., 2004; 115: 409-417
116. Zhang A.S., Xiong S., Tsukamoto H., Enns C.A.: Localization of iron metabolism-related mRNAs in rat liver indicate that HFE is expressed predominantly in hepatocytes. Blood, 2004; 103: 1509-1514