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H63D homozygotes with hyperferritinaemia: Is this genotype, the primary cause of iron overload?

Abstract

OBJECTIVES

Hereditary haemochromatosis is a disease that affects iron metabolism and leads to iron overload. Homozygosity for the H63D mutation is associated with increased transferrin saturation (TS) and ferritin levels. Our objective was to find out if the homozygosity of H63D mutation was the primary cause of iron overload.

PATIENTS AND METHODS

We studied 45 H63D homozygotes (31 males and 14 females) with biochemical iron overload and/or clinical features of haemochromatosis. The simultaneous detection of 18 known HFE, TFR2 and FPN1 mutations and sequencing of the HAMP gene were performed to rule out the possible existence of genetic modifier factors related with iron overload.

RESULTS

Values of biochemical iron overload, measured as percentage TS and serum ferritin concentration (SF), in our H63D homozygotes were significantly higher in patients than in controls: TS 55 +/- 15% vs. 35 +/- 15% and SF 764 (645-883) microg/L vs. 115 (108-123) microg/L for patients and controls, respectively. These H63D homozygotes presented extreme hyperferritinaemia and no additional mutations in HFE, TFR2, FPN1 and HAMP genes were detected.

CONCLUSIONS

The lack of additional mutations in our H63D homozygotes suggests that this genotype could be the primary cause of iron overload in these patients. Despite our results, we cannot entirely discount the possibility that one or more genetic modifier factor exists, simply because we were unable to find it, although there was a precedent in the HFE gene. Genetic modifier factors have been described for C282Y mutations in the HFE gene, but at the present time they have never been reported in H63D homozygotes.

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  • Authors+Show Affiliations

    ,

    Department of Genetics, Hospital Virgen de la Salud, Toledo, Spain. cadedi@sescam.jccm.es

    , ,

    Source

    European journal of haematology 78:1 2007 Jan pg 66-71

    MeSH

    Adolescent
    Adult
    Aged
    Aged, 80 and over
    Amino Acid Substitution
    Female
    Ferritins
    Genotype
    Hemochromatosis
    Homozygote
    Humans
    Iron Metabolism Disorders
    Iron Overload
    Male
    Middle Aged

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17042772

    Citation

    de Diego, Carles, et al. "H63D Homozygotes With Hyperferritinaemia: Is This Genotype, the Primary Cause of Iron Overload?" European Journal of Haematology, vol. 78, no. 1, 2007, pp. 66-71.
    de Diego C, Opazo S, Murga MJ, et al. H63D homozygotes with hyperferritinaemia: Is this genotype, the primary cause of iron overload? Eur J Haematol. 2007;78(1):66-71.
    de Diego, C., Opazo, S., Murga, M. J., & Martínez-Castro, P. (2007). H63D homozygotes with hyperferritinaemia: Is this genotype, the primary cause of iron overload? European Journal of Haematology, 78(1), pp. 66-71.
    de Diego C, et al. H63D Homozygotes With Hyperferritinaemia: Is This Genotype, the Primary Cause of Iron Overload. Eur J Haematol. 2007;78(1):66-71. PubMed PMID: 17042772.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - H63D homozygotes with hyperferritinaemia: Is this genotype, the primary cause of iron overload? AU - de Diego,Carles, AU - Opazo,Sonsoles, AU - Murga,Maria J, AU - Martínez-Castro,Pedro, Y1 - 2006/10/17/ PY - 2006/10/18/pubmed PY - 2007/3/21/medline PY - 2006/10/18/entrez SP - 66 EP - 71 JF - European journal of haematology JO - Eur. J. Haematol. VL - 78 IS - 1 N2 - OBJECTIVES: Hereditary haemochromatosis is a disease that affects iron metabolism and leads to iron overload. Homozygosity for the H63D mutation is associated with increased transferrin saturation (TS) and ferritin levels. Our objective was to find out if the homozygosity of H63D mutation was the primary cause of iron overload. PATIENTS AND METHODS: We studied 45 H63D homozygotes (31 males and 14 females) with biochemical iron overload and/or clinical features of haemochromatosis. The simultaneous detection of 18 known HFE, TFR2 and FPN1 mutations and sequencing of the HAMP gene were performed to rule out the possible existence of genetic modifier factors related with iron overload. RESULTS: Values of biochemical iron overload, measured as percentage TS and serum ferritin concentration (SF), in our H63D homozygotes were significantly higher in patients than in controls: TS 55 +/- 15% vs. 35 +/- 15% and SF 764 (645-883) microg/L vs. 115 (108-123) microg/L for patients and controls, respectively. These H63D homozygotes presented extreme hyperferritinaemia and no additional mutations in HFE, TFR2, FPN1 and HAMP genes were detected. CONCLUSIONS: The lack of additional mutations in our H63D homozygotes suggests that this genotype could be the primary cause of iron overload in these patients. Despite our results, we cannot entirely discount the possibility that one or more genetic modifier factor exists, simply because we were unable to find it, although there was a precedent in the HFE gene. Genetic modifier factors have been described for C282Y mutations in the HFE gene, but at the present time they have never been reported in H63D homozygotes. SN - 0902-4441 UR - https://www.unboundmedicine.com/medline/citation/17042772/H63D_homozygotes_with_hyperferritinaemia:_Is_this_genotype_the_primary_cause_of_iron_overload L2 - https://doi.org/10.1111/j.1600-0609.2006.00775.x DB - PRIME DP - Unbound Medicine ER -