Annals of Hematology

, Volume 88, Issue 3, pp 229–234 | Cite as

Non-classical hereditary hemochromatosis in Portugal: novel mutations identified in iron metabolism-related genes

  • Ana Isabel Mendes
  • Ana Ferro
  • Rute Martins
  • Isabel Picanço
  • Susana Gomes
  • Rute Cerqueira
  • Manuel Correia
  • António Robalo Nunes
  • Jorge Esteves
  • Rita Fleming
  • Paula FaustinoEmail author
Original Article


The most frequent genotype associated with Hereditary hemochromatosis is the homozygosity for C282Y, a common HFE mutation. However, other mutations in HFE, transferrin receptor 2 (TFR2), hemojuvelin (HJV) and hepcidin (HAMP) genes, have also been reported in association with this pathology. A mutational analysis of these genes was carried out in 215 Portuguese iron-overloaded individuals previously characterized as non-C282Y or non-H63D homozygous and non-compound heterozygous. The aim was to determine the influence of these genes in the development of iron overload phenotypes in our population. Regarding HFE, some known mutations were found, as S65C and E277K. In addition, three novel missense mutations (L46W, D129N and Y230F) and one nonsense mutation (Y138X) were identified. In TFR2, besides the I238M polymorphism and the rare IVS5 −9T→A mutation, a novel missense mutation was detected (F280L). Concerning HAMP, the deleterious mutation 5’UTR −25G→A was found once, associated with Juvenile Hemochromatosis. In HJV, the A310G polymorphism, the novel E275E silent alteration and the novel putative splicing mutation (IVS2 +395C→G) were identified. In conclusion, only a few number of mutations which can be linked to iron overload was found, revealing their modest contribution for the development of this phenotype in our population, and suggesting that their screening in routine diagnosis is not cost-effective.


Hereditary hemochromatosis HFE non-C282Y Population screening 



We thank G. Le Gac (Establissement Français du Sang-Bretagne, Brest, France), G. Biasiotto (Università di Brescia, Italy), F. Daraio (Università di Torino, Italy) e A. Roetto (Università di Torino, Italy) for having kindly supplied mutant controls. We also thank the Unidade Laboratorial de Utilização Comum of the National Institute of Health Dr. Ricardo Jorge for technical support.

This work was partially supported by Fundação para a Ciência e a Tecnologia, Programa de Financiamento Plurianual do CIGMH. This work was awarded by Comissão de Fomento da Investigação em Cuidados de Saúde, Ministério da Saúde P.I. no. 130/2007.


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Ana Isabel Mendes
    • 1
  • Ana Ferro
    • 1
  • Rute Martins
    • 1
  • Isabel Picanço
    • 1
  • Susana Gomes
    • 1
  • Rute Cerqueira
    • 2
  • Manuel Correia
    • 2
  • António Robalo Nunes
    • 3
  • Jorge Esteves
    • 4
  • Rita Fleming
    • 5
  • Paula Faustino
    • 1
    • 6
    Email author
  1. 1.Human Genetics CentreNational Institute of Health Dr. Ricardo JorgeLisbonPortugal
  2. 2.Service of GastroenterologySanta Maria da Feira HospitalSanta Maria da FeiraPortugal
  3. 3.Service of Immuno-hemotherapyPulido Valente HospitalLisbonPortugal
  4. 4.Unit of GastroenterologyS. José HospitalLisbonPortugal
  5. 5.Service of Immuno-hemotherapySanta Maria HospitalLisbonPortugal
  6. 6.Centro de Genética HumanaInstituto Nacional de Saúde Dr. Ricardo JorgeLisbonPortugal

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