Iron overload in HFE C282Y heterozygotes at first genetic testing: A strategy for identifying rare HFE variants

Haematologica

Volumn 96, Issue 4, 2011, Pages 507-514

  Aguilar Martinez, Patricia ^a   Grandchamp, Bernard ^b   Cunat, Séverine ^a   Cadet, Estelle ^c   Blanc, François ^a   Nourrit, Marlène ^d   Lassoued, Kaiss ^c   Schved, Jean François ^a   Rochette, Jacques ^c  

^a MONTPELLIER UNIVERSITY HOSPITAL   (France)

^b BICHAT HOSPITAL   (France)

^c UNIVERSITÉ DE PICARDIE JULES VERNE   (France)

^d ETABLISSEMENT FRANÇAIS DU SANG   (France)

Author keywords

Hereditary hemochromatosis; HFE variants; Iron overload

Indexed keywords

HFE PROTEIN; IRON; TRANSFERRIN;

ADULT; AMINO ACID SUBSTITUTION; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; EXON; FEMALE; GENE DELETION; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC VARIABILITY; HEMATOLOGICAL PARAMETERS; HEMOCHROMATOSIS; HETEROZYGOTE; HUMAN; IRON OVERLOAD; LIVER LEVEL; MALE; MISSENSE MUTATION; MOLECULAR MODEL; MOLECULAR PATHOLOGY; MUTATIONAL ANALYSIS; NUCLEOTIDE SEQUENCE; PROTEIN SECONDARY STRUCTURE; PROTEIN STABILITY; TRANSFERRIN SATURATION;

ADULT; ALLELES; FEMALE; FERRITINS; GENE ORDER; GENETIC TESTING; GENETIC VARIATION; HEMOCHROMATOSIS; HETEROZYGOTE; HISTOCOMPATIBILITY ANTIGENS CLASS I; HUMANS; IRON OVERLOAD; MALE; MEMBRANE PROTEINS; MIDDLE AGED; MUTATION;

EID: 79953836125     PISSN: 03906078     EISSN: 15928721     Source Type: Journal    
DOI: 10.3324/haematol.2010.029751     Document Type: Article

References (44)

1. Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromato-sis. Nat Genet. 1996;13(4):399-408.
2. Bulaj ZJ, Griffen LM, Jorde LB, Edwards CQ, Kushner JP. Clinical and biochemical abnormalities in people heterozygous for hemochromatosis. N Engl J Med. 1996;335 (24):1799-805.
3. Smith BC, Gorve J, Guzail MA, Day C P, Daly AK, Burt AD, et al. Heterozygosity for hereditary hemochromatosis is associated with more fibrosis in chronic hepatitis C. Hepatology. 1998;27(6):1695-1699.
4. Mendler MH, Turlin B, Moirand R, Jouanolle AM, Sapey T, Guyader D, et al. Insulin resistance-associated hepatic iron overload. Gastroenterology. 1999;117(5): 1155-1163.
5. Beutler E, Gelbart T, West C, Lee P, Adams M, Blackstone R, et al. Mutation analysis in hereditary hemochromatosis. Blood Cells Mol Dis. 1996;22(2):187-194.
6. Aguilar Martinez P, Biron C, Blanc F, Masmejean C, Jeanjean P, Michel H, et al. Compound heterozygotes for hemochro-matosis gene mutations: may they help to understand the pathophysiology of the disease? Blood Cells Mol Dis. 1997;23(2):269-276.
7. Brissot P, Moirand R, Jouanolle AM, Guyader D, Le Gall JY, Deugnier Y, et al. A genotypic study of 217 unrelated probands diagnosed as genetic hemochromatosis on classical phenotypic criteria. J Hepatol. 1999;30(4):588-593.
8. Phatak PD, Ryan DH, Cappuccio J, Oakes D, Braggins C, Provenzano K, et al. Prevalence and penetrance of HFE mutations in 4865 unselected primary care patients. Blood Cells Mol Dis. 2002;29(1): 41-47.
9. Crawford DH, Jazwinska EC, Cullen LM, Powell LW. Expression of HLA-linked hemochromatosis in subjects homozygous or heterozygous for the C282Y mutation. Gastroenterology. 1998;114(5):1003-1008.
10. 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(8):2502-2505.
11. Barton JC, Sawada-Hirai R, Rothenberg BE, Acton RT. Two novel missense mutations of the HFE gene (I105T and G93R) and identification of the S65C mutation in Alabama hemochromatosis probands. Blood Cells Mol Dis. 1999;25(3-4):147-155.
12. Le Gac G, Dupradeau FY, Mura C, Jacolot S, Scotet V, Esnault G, et al. Phenotypic expression of the C282Y/Q283P compound heterozygosity in HFE and molecular modeling of the Q283P mutation effect. Blood Cells Mol Dis. 2003;30(3):231-237.
13. Bacon BR, Olynyk JK, Brunt EM, Britton RS, Wolff RK. HFE genotype in patients with hemochromatosis and other liver diseases. Ann Intern Med. 1999;130(12):953-962.
14. Hanson EH, Imperatore G, Burke W. HFE gene and hereditary hemochromatosis: a HuGE review. Human genome epidemiology. Am J Epidemiol. 2001;154 (3):193-206.
15. Biasiotto G, Belloli S, Ruggeri G, Zanella I, Gerardi G, Corrado M, et al. 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(12):1981-1988.
16. Robson KJ, Merryweather-Clarke AT, Cadet E, Viprakasit V, Zaahl MG, Pointon JJ, et al. Recent advances in understanding haemochromatosis: a transition state. J Med Genet. 2004;41(10):721-730.
17. Adams P, Brissot P, Powell LW. EASL International Consensus Conference on Haemochromatosis. J Hepatol. 2000;33(3): 485-504.
18. Gandon Y, Olivie D, Guyader D, Aube C, Oberti F, Sebille V, et al. Non-invasive assessment of hepatic iron stores by MRI. Lancet. 2004;363(9406):357-362.
19. Cunat S, Giansily-Blaizot M, Bismuth M, Blanc F, Dereure O, Larrey D, et al. Global sequencing approach for characterizing the molecular background of hereditary iron disorders. Clin Chem. 2007;53(12):2060-2090.
20. Pointon JJ, Lok CY, Shearman JD, Suckling RJ, Rochette J, Merryweather-Clarke AT, et al. A novel HFE mutation (c.del478) results in nonsense-mediated decay of the mutant transcript in a hemochromatosis patient. Blood Cells Mol Dis. 2009;43(2):194-198.
21. Guruprasad K, Reddy BV, Pandit MW. Correlation between stability of a protein and its dipeptide composition: a novel approach for predicting in vivo stability of a protein from its primary sequence. Protein Eng. 1990;4(2):155-161.
22. Lebron JA, Bennett MJ, Vaughn DE, Chirino AJ, Snow PM, Mintier GA, et al. Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell. 1998;93(1):111-123.
23. Bennett MJ, Lebron JA, Bjorkman PJ. Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor. Nature. 2000;403 (6765):46-53.
24. Humphrey W, Dalke A, Schulten K. VMD: visual molecular dynamics. J Mol Graph. 1996;14(1):33-38.
25. Powell EE, Ali A, Clouston AD, Dixon JL, Lincoln DJ, Purdie DM, et al. Steatosis is a cofactor in liver injury in hemochromatosis. Gastroenterology. 2005;129(6):1937-1943.
26. Swinkels DW, Venselaar H, Wiegerinck ET, Bakker E, Joosten I, Jaspers CA, et al. A novel (Leu183Pro) mutation in the HFE-gene co-inherited with the Cys282Tyr mutation in two unrelated Dutch hemochromatosis patients. Blood Cells Mol Dis. 2008;40(3):334-338.
27. Allen KJ, Gurrin LC, Constantine CC, Osborne NJ, Delatycki MB, Nicoll AJ, et al. Iron-overload-related disease in HFE hereditary hemochromatosis. N Engl J Med. 2008;358(3):221-230.
28. Aguilar-Martinez P, Bismuth M, Blanc F, Blanc P, Cunat S, Dereure O, et al. The Southern French registry of genetic hemochromatosis: a tool for determining clinical prevalence of the disorder and genotype penetrance. Haematologica. 2010;95(4):551-556.
29. Deugnier Y, Jouanolle AM, Chaperon J, Moirand R, Pithois C, Meyer JF, et al. Gender-specific phenotypic expression and screening strategies in C282Y-linked haemochromatosis: a study of 9396 French people. Br J Haematol. 2002;118(4):1170-1178.
30. Lebron JA, Bjorkman PJ. The transferrin receptor binding site on HFE, the class I MHC-related protein mutated in hereditary hemochromatosis. J Mol Biol. 1999;289(4): 1109-1118.
31. Dupradeau FY, Pissard S, Coulhon MP, Cadet E, Foulon K, Fourcade C, et al. An unusual case of hemochromatosis due to a new compound heterozygosity in HFE (p.[Gly43Asp;His63Asp]+[Cys282Tyr]): structural implications with respect to binding with transferrin receptor 1. Hum Mutat. 2008;29(1):206.
32. Menardi G, Perotti L, Prucca M, Martini S, Prandi G, Peano G. A very rare association of three mutations of the HFE gene for hemochromatosis. Genet Test. 2002;6(4): 331-334.
33. Kinkely SM, Brown BD, Lyng AT, Harrison WK, Schep GN, Goddard-Hill AC, et al. Absence of overt iron overload in two individuals compound heterozygotes for a 22 base pair deletion of exon 2 and the C282Y missense mutation of the HFE gene. Clin Genet. 2003;63(2):163-165.
34. Brissot P, de Bels F. Current approaches to the management of hemochromatosis. Hematology Am Soc Hematol Educ Program. 2006:36-41.
35. Mariani R, Pelucchi S, Arosio C, Coletti S, Pozzi M, Paolini V, et al. Genetic and metabolic factors are associated with increased hepatic iron stores in a selected population of p.Cys282Tyr heterozygotes. Blood Cells Mol Dis. 2010;44(3):159-163.
36. European Association For The Study Of The L. EASL clinical practice guidelines for HFE hemochromatosis. J Hepatol. 2010;53 (1):3-22.
37. Thorstensen K, Kvitland MA, Irgens WO, Hveem K, Asberg A. Screening for C282Y homozygosity in a Norwegian population (HUNT2): the sensitivity and specificity of transferrin saturation. Scand J Clin Lab Invest. 2010;70(2):92-97.
38. Merryweather-Clarke AT, Cadet E, Bomford A, Capron D, Viprakasit V, Miller A, et al. Digenic inheritance of mutations in HAMP and HFE results in different types of haemochromatosis. Hum Mol Genet. 2003; 12(17):2241-2247.
39. Wallace DF, Dooley JS, Walker AP. A novel mutation of HFE explains the classical phe-notype of genetic hemochromatosis in a C282Y heterozygote. Gastroenterology. 1999;116(6):1409-1412.
40. Liechti-Gallati S, Varga D, Reichen J. Screening for haemochromatosis in Switzerland: detection of a new pathogenic mutation and two additional variants in exon 2 of the HFE gene. In: European Society of Human Genetics; 1999; Geneva, Switzerland; 1999. p. 122.
41. Piperno A, Arosio C, Fossati L, Vigano M, Trombini P, Vergani A, et al. Two novel nonsense mutations of HFE gene in five unrelated Italian patients with hemochro-matosis. Gastroenterology. 2000;119(2): 441-445.
42. Beutler E, Griffin MJ, Gelbart T, West C. A previously undescribed nonsense mutation of the HFE gene. Clin Genet. 2002;61(1):40-42.
43. Barton JC, West C, Lee PL, Beutler E. A previously undescribed frameshift deletion mutation of HFE (c.del277; G93fs) associated with hemochromatosis and iron overload in a C282Y heterozygote. Clin Genet. 2004;66(3):214-216.
44. Mendes AI, Ferro A, Martins R, Picanco I, Gomes S, Cerqueira R, et al. Non-classical hereditary hemochromatosis in Portugal: novel mutations identified in iron metabolism-related genes. Ann Hematol. 2009;88 (3):229-234.