Published online 14 January 2009
Haematologica, Vol 94, Issue 2, 276-279 doi:10.3324/haematol.13576
Copyright © 2009 by Ferrata Storti Foundation
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Disorders of Iron Metabolism

Expression of hepcidin and other iron-related genes in type 3 hemochromatosis due to a novel mutation in transferrin receptor-2

Sara Pelucchi1,2, Raffaella Mariani2,3, Paola Trombini3, Sabina Coletti2,3, Matteo Pozzi2,3, Valentina Paolini2,3, Donatella Barisani4, Alberto Piperno1,2,3

1 Consortium for Human Molecular Genetics, Monza, Milan
2 Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Monza, Milan
3 Clinical Medicine, San Gerardo Hospital, Monza, Milan and
4 Department of Experimental Medicine, University of Milano-Bicocca, Monza, Milan, Italy

Correspondence: Alberto Piperno, Clinica Medica, Università di Milano-Bicocca, Azienda Ospedaliera San Gerardo, Via Pergolesi, 33 - 20052 Monza (MI) E-mail:alberto.piperno{at}unimib.it

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.

Key words: TFR2, hepcidin, hepatic expression, iron overload, splicing mutation.