title: Expression of hepcidin and other iron-related genes in type 3 hemochromatosis due to a novel mutation in transferrin receptor-2.
abstract: Transferrin receptor-2 (TFR2) regulates hepatic hepcidin secretion and when mutated causes type-3 hemochromatosis. No functional study is available in humans. We studied a 47 year-old woman with hemochromatosis. TFR2 DNA and its hepatic transcript were directly sequenced. Hepatic expression of hepcidin and other iron-related genes were measured by qRT-PCR. Urinary hepcidin was measured at baseline and after an oral iron challenge (ferrous sulfate, 65 mg) by SELDI-TOF-MS. A novel homozygous TFR2 mutation was identified in the splicing donor site of intron 4 (c.614+4 A>G) causing exon 4 skipping. Hepcidin and hemojuvelin expression were markedly reduced. Urinary hepcidin was lower than normal and further decreased after iron challenge. This is the first description of iron-related gene expression profiles in a TFR2 mutated patient. The decreased hepatic and urinary expression of hepcidin and lack of acute response to iron challenge confirms the primary role of TFR2 in iron homeostasis.
authors.affiliation: Consortium for Human Molecular Genetics, Monza, Milan.
authors.forename: Sara
authors.initials: S
authors.lastname: Pelucchi
authors.forename: Raffaella
authors.initials: R
authors.lastname: Mariani
authors.forename: Paola
authors.initials: P
authors.lastname: Trombini
authors.forename: Sabina
authors.initials: S
authors.lastname: Coletti
authors.forename: Matteo
authors.initials: M
authors.lastname: Pozzi
authors.forename: Valentina
authors.initials: V
authors.lastname: Paolini
authors.forename: Donatella
authors.initials: D
authors.lastname: Barisani
authors.forename: Alberto
authors.initials: A
authors.lastname: Piperno
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000652:urine; D005260:Female; D020869:Gene Expression Profiling; D006432:Hemochromatosis / Q000235:genetics*; D064451:Hepcidins; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011990:Receptors, Transferrin / Q000235:genetics*
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D011990:Receptors, Transferrin; C503640:TFR2 protein, human