@article{Marie-Laure Island_Anne-Marie Jouanolle_Annick Mosser_Yves Deugnier_Véronique David_Pierre Brissot_Olivier Loréal_2009, place={Pavia, Italy}, title={A new mutation in the hepcidin promoter impairs its BMP response and contributes to a severe phenotype in HFE related hemochromatosis}, volume={94}, url={https://haematologica.org/article/view/5251}, DOI={10.3324/haematol.2008.001784}, abstractNote={Low levels of hepcidin are responsible for the development of iron overload in p.Cys282Tyr <em>HFE</em> related hemochromatosis. Every genetic factor lowering the hepcidin gene expression could contribute to a more severe phenotype in <em>HFE</em> hemochromatosis. Based on this hypothesis, we identified a heterozygous nc.-153 C>T mutation in the hepcidin gene promoter sequence in a patient homozygous for the p.Cys282Tyr <em>HFE</em> mutation who presented massive iron overload, resisting to well conducted iron depletive treatment. Our results demonstrate that the nc.-153 C&gt;T mutation, located within a BMP-RE (Bone Morphogenetic Protein-Responsive Element): i) decreases the transcriptional activity of the hepcidin promoter, ii) alters its IL-6 (Interleukin-6) total responsiveness, and iii) prevents the binding of the SMAD protein complex (1/5/8 and 4) to the BPM-RE. In conclusion, our results suggest that a mutation in the BMP-RE of hepcidin promoter may impact on human iron metabolism.}, number={5}, journal={Haematologica}, author={Marie-Laure Island and Anne-Marie Jouanolle and Annick Mosser and Yves Deugnier and Véronique David and Pierre Brissot and Olivier Loréal}, year={2009}, month={Apr.}, pages={720-724} }