Severe hemochromatosis in a Portuguese family associated with a new mutation in the 5'-UTR of the HAMP gene

Article Article scientifique Rapport de cas Severe hemochromatosis in a Portuguese family associated with a new mutation in the 5'-UTR of the HAMP gene eng 2004-06-15 2004-10-01 author Matthes Thomas 27368 author Aguilar Patricia 563953 author Pizzi-Bosman Loredana 914433 author Darbellay Régis 858117 author Rubbia-Brandt Laura 31809 author Giostra Emilio author Michel Martine author Ganz Tomas author Beris Photis 26494 2181-2183 10.1182/blood-2004-01-0332 15198949 0006-4971 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. 5' Untranslated Regions Adult Antimicrobial Cationic Peptides / genetics Antimicrobial Cationic Peptides / metabolism Antimicrobial Cationic Peptides / physiology Base Sequence Blotting, Western Codon DNA / chemistry DNA, Complementary / metabolism Family Health Female GPI-Linked Proteins Hemochromatosis / ethnology Hemochromatosis / genetics Hemochromatosis Protein Hepcidins Humans Inflammation Iron / chemistry Iron / metabolism Iron Overload Male Membrane Proteins / genetics Molecular Sequence Data Mutation Phenotype Portugal Protein Biosynthesis RNA / chemistry Time Factors Dewey 616 Dewey 616.07 56 Département de médecine 221 137 Département de pathologie et immunologie 21F false 586 Analyses cellulaires et moléculaires des hémopathies malignes 929 391 Métastases du foie 657 Blood 104 7 a3eca66a-88c8-4752-bd18-13f1d35d2ad2 Article (Published version) Public 1-s2.0-S0006497120433816-main.pdf 125190 application/pdf OA OTHER openAccess Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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Severe hemochromatosis in a Portuguese family associated with a new mutation in the 5'-UTR of the HAMP gene	Blood			2004	122	132

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Aguilar, Patricia