Novel mutations of the ferroportin gene (SLC40A1): Analysis of 56 consecutive patients with unexplained iron overload

Clinical Genetics

Volumn 73, Issue 2, 2008, Pages 171-178

  Pelucchi, S ^a   Mariani, R ^b   Salvioni, A ^b   Bonfadini, S ^b   Riva, A ^b   Bertola, F ^a   Trombini, P ^b   Piperno, Alberto ^a,b  

^a Consortium for Human Molecular Genetics ^*  (Italy)

^b SAN GERARDO HOSPITAL   (Italy)

Author keywords

Ferroportin; Hyperferritinemia; Iron overload; Phenotype heterogeneity

Indexed keywords

CATION TRANSPORT PROTEIN; FERRITIN; IRON; METAL TRANSPORTING PROTEIN 1; TRANSFERRIN; UNCLASSIFIED DRUG;

ADULT; AGED; AMINO ACID SUBSTITUTION; ARTICLE; BLOOD; CASE REPORT; FEMALE; GENETICS; HUMAN; IRON OVERLOAD; MALE; METABOLISM; MIDDLE AGED; PEDIGREE; PENETRANCE;

ADULT; AGED; AMINO ACID SUBSTITUTION; CATION TRANSPORT PROTEINS; FEMALE; FERRITINS; HUMANS; IRON; IRON OVERLOAD; MALE; MIDDLE AGED; PEDIGREE; PENETRANCE; TRANSFERRIN;

EID: 38349111469     PISSN: 00099163     EISSN: 13990004     Source Type: Journal    
DOI: 10.1111/j.1399-0004.2007.00950.x     Document Type: Article

References (45)

1. Bothwell TH, Charlton RW, Motulsky AG. Hemochromatosis. In: Scriver CR, Beudet AL, Sly WS et al. The metabolic and molecular bases of inherited disease, 7th edn. New York: McGraw-Hill, 1995: 2237-2269.
2. Camaschella C. Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders. Blood 2005; 106:3710-3717.
3. 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.
4. Pietrangelo A. Hereditary hemochromatosis - a new look at an old disease. N Engl J Med 2004; 350:2383-2397.
5. 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.
6. Papanikolaou G, Samuels ME, Ludwig EH et a. Mutations in HFE2 cause iron overload in chromosome 1q- linked juvenile hemochromatosis. Nat Genet 2004; 36:77-82.
7. Roetto A, Papanikolaou G, Politou M et al. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet 2003; 33:21-22.
8. Camaschella C, Roetto A, Cali A et al. The gene TfR2 is mutated in a new type of haemochromatosis. Nat Genet 2000; 25:14-15.
9. Roetto A, Totaro A, Piperno A et al. New mutations inactivating transferrin receptor 2 in hemochromatosis type 3. Blood 2001; 97:2555-2560.
10. Pietrangelo A. The ferroportin disease. Blood Cells Mol Dis 2004; 32:131-138.
11. Donovan A, Brownlie A, Zhou Y et al. Positional cloning of zebrafish ferroportin identifies a conserved vertebrate iron exporter. Nature 2000; 403:776-781.
12. McKie AT, Marciani P, Rolfs A et al. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell 2000; 5:299-309.
13. Arden KE, Wallace DF, Dixon JL et al. A novel mutation in ferroportin 1 is associated with haemachromatosis in a Solomon Islands patient. Gut 2003; 52:1215-1217.
14. Wallace DF, Browett P, P Wong et al. Identification of ferroportin disease in the Indian subcontinent. Gut 2004; 54:567-568.
15. Jouanolle AM, Douabin-Gicquel V, Halimi C et al. Novel mutation in ferroportin 1 gene is associated with autosomal dominant iron overload. J Hepatol 2003; 39:286-289.
16. Gordeuk VR, Caleffi A, Corradini E et al. 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.
17. Beutler E, Burton JC, Felitti VJ et al. Ferroportin 1 (SLC40A1) variant is associated with iron overload in African-Americans. Blood Cells Mol Dis 2003; 31:305-309.
18. Koyama C, Wakusawa S, Hayashi H et al. 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.
19. Subramaniam VN, Wallace DF, Dixon JF et al. Ferroportin disease due to the A77D mutation in Australia. Gut 2005; 54:1048-1049.
20. Morris TJ, Litvinova MM, Ralston D et al. A novel ferroportin mutation in a Canadian family with autosomal dominant hemochromatosis. Blood Cells Mol Dis 2005; 35:309-314.
21. Bach V, Remacha A, Altés A et al. Autosomal dominant hereditary hemochromatosis associated with two novel ferroportin 1 mutations in Spain. Blood Cells Mol Dis 2006; 36:41-45.
22. Cazzola M. Genetic disorders of iron overload and the novel "ferroportin disease". Haematologica 2003; 88:721-724.
23. De Domenico I, McVey Ward D, Musci G, Kaplan J. Iron overload due to mutations in ferroportin. Haematologica 2006; 91:92-95.
24. De Domenico I, Ward DM, Nemeth E et al. The molecular basis of ferroportin-linked hemochromatosis. Proc Natl Acad Sci U S A 2005; 102:8955-8960.
25. Nemeth E. Ferroportin mutations: a tale of two phenotypes. Blood 2005; 105:3763-3764.
26. Schimanski LM, Drakesmith H, Merryweather-Clarke AT et al. In vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations. Blood 2005; 105:4096-4102.
27. Mendler MH, Turlin B, Moirand R et al. Insulin resistance- associated hepatic iron overload. Gastroenterology 1999; 117:1155-1163.
28. Kleiner DE, Brunt EM, Van Natta M et al. Design and validation of a histological scoring system for non-alcoholic fatty liver disease. Hepatology 2005; 41:1313-1321.
29. Deugnier YM, Loréal O, Turlin B et al. Liver pathology in genetic hemochromatosis: a review of 135 homozygous cases and their bioclinical correlations. Gastroenterology 1992; 102:2050-2059.
30. Deugnier YM, Turlin B, Powell LW et al. Differentiation between heterozygotes and homozygotes in genetic hemochromatosis by means of histological hepatic iron index: a study of 192 cases. Hepatology 1993; 17:30-34.
31. Devalia V, Carter K, Walker AP et al. Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3). Blood 2002; 100:695-697.
32. Lee PL, Gelbart T, West C et al. A study of genes that may modulate the expression of hereditary hemochromatosis: transferrin receptor-1, ferroportin, ceruloplasmin, ferritin light and heavy chains, iron regulatory proteins (IRP)-1 and -2, and hepcidin. Blood Cells Mol Dis 2001; 114:474-484.
33. Ishak K, Baptista A, Bianchi L et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22:696-699.
34. Piperno A, Arosio C, Fargion S et al. The ancestral hemochromatosis haplotype is associated with a severe phenotype expression in Italian patients. Hepatology 1996; 24:43-46.
35. Hetet G, Devaux I, Soufir N et al. 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.
36. Rivard SR, Lanzara C, Grimard D et al. Autosomal dominant reticuloendothelial iron overload (HFE type 4) due to a new missense mutation in the ferroportin 1 gene (SLC11A3) in a large French-Canadian family. Haematologica 2003; 88:824-825.
37. Montosi G, Donovan A, Totaro A et al. Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. J Clin Invest 2001; 108:619-623.
38. Corradini E, Montosi G, Ferrara F et al. Lack of enterocytes iron accumulation in ferroportin disease. Blood Cells Mol Dis 2005; 35:315-318.
39. Liu XB, Yang F, Haile DJ et al. Functional consequences of ferroportin 1 mutations. Blood Cells Mol Dis 2005; 35:33-46.
40. Trombini P, Piperno A. Ferritin, metabolic syndrome and NAFLD: elective attractions and dangerous liaisons. J Hepatol 2007; 46:549-552.
41. Piperno A. Classification and diagnosis of iron overload. Haematologica 1998; 83:447-455.
42. Turlin B, Mendler MH, Moirand R et al. Histologic feature of the liver in insulin resistance-associated iron overload. Am J Clin Pathol 2001; 116:263-270.
43. Roecker L, Meier-Buttermilch R, Brechtel L et al. Iron-regulatory protein hepcidin is increased in female athletes after a marathon. Eur J Appl Physiol 2005; 95:569-571.
44. Weight LM, Byrne MJ, Jacobs P. Haemolytic effects of exercise. Clin Sci (Lond) 1991; 81:147-152.
45. Wang F, ParadKar PN, Custodio AO et al. Genetic variation in Mon1a affects protein trafficking and modifies macrophage iron loading in mice. Nat Genet 2007; 39:1025-1032.