Severe hemochromatosis in a Portuguese family associated with a new mutation in the 5′-UTR of the HAMP gene
| Autor: | Emilio Giostra, Loredana Pizzi-Bosman, Martine Michel, Tomas Ganz, Thomas Matthes, R. Darbellay, Patricia Aguilar-Martinez, Photis Beris, Laura Rubbia-Brandt |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male DNA Complementary Iron Overload Time Factors Five prime untranslated region Iron Kozak consensus sequence Blotting Western Molecular Sequence Data Immunology GPI-Linked Proteins Biochemistry Autosomal recessive trait Hepcidins Hepcidin medicine Humans Codon Hemochromatosis Protein Hemochromatosis Family Health Inflammation Genetics Base Sequence Portugal biology Membrane Proteins DNA Cell Biology Hematology medicine.disease Juvenile hemochromatosis Phenotype Protein Biosynthesis Hereditary hemochromatosis Mutation biology.protein RNA Female HAMP 5' Untranslated Regions Antimicrobial Cationic Peptides |
| Zdroj: | Blood. 104:2181-2183 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2004-01-0332 |
| Popis: | Juvenile hereditary hemochromatosis is a genetically heterogeneous disorder transmitted as an autosomal recessive trait. It is most often caused by mutations in the HJV gene and rarely in the HAMP gene. Hepcidin is considered to constitute a negative regulator of iron absorption, and its production is increased in inflammatory states and iron overload. We report the detection of a new mutation in the HAMP gene leading to juvenile hemochromatosis in 2 members of a Portuguese family. The mutation lies in the 5′-UTR (untranslated region) of the gene and creates a new initiation codon in the context of a Kozak sequence. We found no trace of hepcidin protein in the patients' urine, suggesting that ribosomes select the mutant initiation codon for translation. The decrease of hepcidin production would thus lead to increased iron absorption, resulting in iron deposition in parenchymal tissues. Phlebotomy therapy of the 2 patients resulted in impressive clinical improvement. (Blood. 2004;104: 2181-2183) |
| Databáze: | OpenAIRE |
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