Abstract
Since the discovery of the HFE gene, C282Y and H63D mutations have been reported as significantly correlated with clinically manifested hereditary hemochromatosis (HH). As the other genes involved in iron metabolism have been described, non-HFE cases of HH have been identified. Since in the general Turkish population, the C282Y mutation is not found and the H63D mutation is of high frequency, we aimed to determine mutations in the HFE genes in our patients with HH. The HFE gene of the five patients with HH were sequenced. C282Y mutation was absent, and all HH patients were heterozygote for H63D mutation. No other mutation was found in HFE gene by sequencing. Although the higher allele frequency of the H63D mutation in Turkish HH patients than in the general population implies a role of the H63D mutation in iron overload, there is a strong possibility that Turkish HH patients have non-HFE hemochromatosis.
This is a preview of subscription content, log in via an institution to check access.
References
Adams PC (1999) Population screening for hemochromatosis. Hepatology 29:1324–1327
Harrison SA, Bacon BR (2005) Relation of hemochromatosis with hepatocellular carcinoma: epidemiology, natural history, pathophysiology, screening, treatment, and prevention. Med Clin North Am 89:391–409
Felitti VJ, Beutler E (1999) New developments in hereditary hemochromatosis. Am J Med Sci 318:257–268
Niederau C, Fisher R, Purschel A, Stremmel W, Haussinger D et al (1996) Long-term survival in patients with hereditary hemachromatosis. Gastroenterology 110:1107–1119
Hanson EH, Imperatore G, Burke W (2001) HFE gene and hereditary hemochromatosis: a HuGE review. Human genome epidemiology. Am J Epidemiol 154:193–206
Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA et al (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13:399–408
The UK Haemochromatosis Consortium (1997) A simple genetic test identifies 90% of UK patients with haemochromatosis. Gut 41:841–844
Camaschella C, Fargion S, Sampietro M, Roetto A, Bosio S et al (1999) Inherited HFE-unrelated hemochromatosis in Italian families. Hepatology 29:1563–1564
Aguilar-Martinez P, Bismuth M, Picot MC, Thelcide C, Pageaux GP et al (2001) Variable phenotypic presentation of iron overload in H63D homozygotes: are genetic modifiers the cause? Gut 48:836–842
Merryweather-Clarke AT, Pointon JJ, Shearman JD, Robson KJH (1997) Global prevalence of putative haemochromatosis mutations. J Med Genet 34:275–278
Bomford A (2002) Genetics of haemochromatosis. Lancet 360:1673–1681
Milman N, A Steig T, Koefoed P, Pedersen P, Fenger K, Nielsen FC (2005) Frequency of the hemochromatosis HFE mutations C282Y, H63D, and S65C in blood donors in the Faroe Islands. Ann Hematol 84:146–149
Milman N, Pedersen P, Ovesen L, Melsen GV, Fenger K (2004) Frequency of the C282Y and H63D mutations of the hemochromatosis gene (HFE) in 2501 ethnic Danes. Ann Hematol 83:654–657
Bauduer F, Scribans C, Degioanni A, Renoux M, Dutour O (2005) Distribution of the C282Y and H63D polymorphisms in hereditary hemochromatosis patients from the French Basque country. Ann Hematol 84:99–102
Simsek H, Sumer H, Yilmaz E, Balaban YH, Ozcebe O, Hascelik G, Buyukask Y, Tatar G (2004) Frequency of HFE mutations among Turkish blood donors according to transferrin saturation. J Clin Gastroenterol 38:671–675
El-Serag HB, Inadomi JM, Kowdley KV (2000) Screening for hereditary hemochromatosis in siblings and children of affected patients. A cost-effectiveness analysis. Ann Intern Med 132:261–269
Adams PC (2000) Population screening for hemochromatosis. Gut 46:301–303
EASL (2000) International consensus conference on hemochromatosis. J Hepatol 33:485–504
Krawczak M, Cooper DN, Schmidtke J (2001) Estimating the efficacy and efficiency of cascade genetic screening. Am J Hum Genet 69:361–370
Papanikolaou G, Politou M, Roetto A et al (2001) Linkage to chromosome 1q in Greek families with juvenile hemochromatosis. Blood Cells Mol Dis 27(4):744–749
Wallace DF, Pedersen P, Dixon JL et al (2002) Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis. Blood 100:692–694
Barosia G, Salvaneschi L, Grasso M et al (2002) High prevalence of screening-detected, HFE-unrelated, mild idiopathic iron overload in northern Italy. Haematologica 87(5):472–478
Montosi G, Donovan A, Totaro A et al (2001) Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. J Clin Invest 108(4):521–522
Piperno A, Arosio C, Fossati L et al (2000) Two novel nonsense mutations of HFE gene in five unrelated Italian patients with hemochromatosis. Gastroenterology 119(2):441–445
Pietrangelo A, Montosi G, Totaro A et al (1999) Hereditary hemochromatosis in adults without pathogenic mutations in the hemochromatosis gene. N Engl J Med 341(10):725–727
Njajou OT, Vaessen N, Joosse M et al (2001) A mutation in SCL11A3 is associated with autosomal dominant hemochromatosis. Nat Genet 28:213–214
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Simsek, H., Balaban, Y.H., Yilmaz, E. et al. Mutations of the HFE gene among Turkish hereditary hemochromatosis patients. Ann Hematol 84, 646–649 (2005). https://doi.org/10.1007/s00277-005-1048-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-005-1048-y