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ABSTRACT: Hereditary hemochromatosis causes iron overload and is associated with a variety of genetic and phenotypic conditions. Early diagnosis is important so that effective treatment can be administered and the risk of tissue damage avoided. Most patients are homozygous for the c.845G>A (p.C282Y) mutation in the HFE gene; however, rare forms of genetic iron overload must be diagnosed using a specific genetic analysis. We studied the genotype of 5 patients who had hyperferritinemia and an iron overload phenotype, but not classic mutations in the HFE gene. Two patients were undergoing phlebotomy and had no iron overload, 1 with metabolic syndrome and no phlebotomy had mild iron overload, and 2 patients had severe iron overload despite phlebotomy. The patients' first-degree relatives also underwent the analysis. We found 5 not previously published mutations: c.-408_-406delCAA in HFE, c.1118G>A (p.G373D), c.1473G>A (p.E491E) and c.2085G>C (p.S695S) in TFR2; and c.-428_-427GG>TT in SLC40A1. Moreover, we found 3 previously published mutations: c.221C>T (p.R71X) in HFE; c.1127C>A (p.A376D) in TFR2; and c.539T>C (p.I180T) in SLC40A1. Four patients were double heterozygous or compound heterozygous for the mutations mentioned above, and the patient with metabolic syndrome was heterozygous for a mutation in the TFR2 gene. Our findings show that hereditary hemochromatosis is clinically and genetically heterogeneous and that acquired factors may modify or determine the phenotype.
Gene 08/2012; 508(1):15-20. · 2.34 Impact Factor
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British Journal of Haematology 02/2012; 157(4):514-6. · 4.94 Impact Factor
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ABSTRACT: Hyperferritinemia is a common finding in clinical practice. This condition can be congenital or acquired, although it is not always associated with iron overload. Genetic hyperferritinemia is associated with iron overload, hereditary hemochromatosis, or cataracts that progress without iron overload (hereditary hyperferritinemia-cataract syndrome). Metabolic syndrome is associated with hyperferritinemia and mild iron overload, with no increase in transferrin saturation. We report a family with hyperferritinemia.
We present the study of a family with dual hyperferritinemia (congenital and acquired) and an analysis of the genes involved in iron metabolism.
Patients with hereditary hyperferritinemia-cataract syndrome have the mutation c.-167C>T in the FTL gene; patients with metabolic syndrome present a new mutation in the TFR2 gene (c.1259G>A, p.Arg420His).
The phenotypic and genotypic diversity of hyperferritinemia makes it a diagnostic challenge for clinicians. Basic research and clinical research should be combined to ensure better patient care.
Medicina Clínica 06/2011; 137(2):68-72. · 1.38 Impact Factor
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ABSTRACT: The most common form of hemochromatosis is caused by mutations in the HFE gene. Rare forms of the disease are caused by mutations in other genes. We present a patient with hyperferritinemia and iron overload, and facial flushing. Magnetic resonance imaging was performed to measure hepatic iron overload, and a molecular study of the genes involved in iron metabolism was undertaken. The iron overload was similar to that observed in HFE hemochromatosis, and the patient was double heterozygous for two novel mutations, c.-20G>A and c.718A>G (p.K240E), in the HFE and ferroportin (FPN1 or SLC40A1) genes, respectively. Hyperferritinemia and facial flushing improved after phlebotomy. Two of the patient's children were also studied, and the daughter was heterozygous for the mutation in the SLC40A1 gene, although she did not have hyperferritinemia. The patient presented a mild iron overload phenotype probably because of the two novel mutations in the HFE and SLC40A1 genes.
European Journal Of Haematology 03/2011; 86(3):260-4. · 2.61 Impact Factor
