HAMP promoter mutation nc.-153C>T in 785 HEIRS Study participants

We thank Barton and collaborators who gave their attention to our recent publication in Haematologica1 on the –nc.153 C>T mutation found at heterozygous state in the hepcidin promoter of a patient homozygous for the C282Y mutation in HFE with an extremely severe form of genetic hemochromatosis. We found that this mutation may strongly affect the hepcidin promoter activity, especially by impairing its BMP/SMAD activation response, and thus could contribute to the severe phenotype of the patient.

The results of Barton et al.,2 obtained from a large panel of patients selected from the HEIRS study, support the fact that this mutation is extremely rare, leading them to not recommend a large screening for this mutation in hemochromatosis patients. In addition, they found that a patient presenting with an hyperferritinemia, which was not confirmed thereafter, also has a nc.-443 C>T mutation in addition to the nc.-153 C>T in the hepcidin promoter.

We fully agree with Barton and collaborators, that from available data, there is no need to systematically search for the nc.-153 C>T hepcidin promoter mutation during population based studies and iron overload screening programs. However, in selected patients with proved and not fully explained iron overload phenotypes with high plasma transferrin saturation, future studies of the presence of the nc.-153 C>T, together with family studies, which was not possible in the patient that we reported, should provide valuable information on the clinical impact of this mutation in atypical iron overload conditions.