| 19144662 |
Pelucchi S, Mariani R, Trombini P, Coletti S, Pozzi M, Paolini V, Barisani D, Piperno A: Expression of hepcidin and other iron-related genes in type 3 hemochromatosis due to a novel mutation in transferrin receptor-2. Haematologica. 2009 Feb;94(2):276-9. Epub 2009 Jan 14.
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. |
12(0,0,1,7) |