论文信息 - Molecular mechanism of hepcidin deficiency in a patient with juvenile hemochromatosis.

Molecular mechanism of hepcidin deficiency in a patient with juvenile hemochromatosis.

We describe a point mutation creating an additional ATG codon in the 5' untranslated region (UTR) of the HAMP gene, in a patient with juvenile hemochromatosis. By transient in vitro transfection studies, we provide evidence that the additional ATG is functional and prevents normal hepcidin production by inducing an aberrant translation initiation of the pre-hepcidin mRNA.

[1] T. Ganz,et al. A Portuguese patient homozygous for the -25G>A mutation of the HAMP promoter shows evidence of steady-state transcription but fails to up-regulate hepcidin levels by iron. , 2005, Blood.

[2] L. Rubbia‐Brandt,et al. Severe hemochromatosis in a Portuguese family associated with a new mutation in the 5'-UTR of the HAMP gene. , 2004, Blood.

[3] M. Cazzola,et al. Spectrum of hemojuvelin gene mutations in 1q-linked juvenile hemochromatosis. , 2004, Blood.

[4] D. Girelli,et al. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis , 2003, Nature Genetics.

[5] M. Kozak,et al. Emerging links between initiation of translation and human diseases , 2002, Mammalian Genome.

[6] G. Mize,et al. Role of two upstream open reading frames in the translational control of oncogene mdm2 , 1999, Oncogene.

[7] David Hogg,et al. Mutation of the CDKN2A 5' UTR creates an aberrant initiation codon and predisposes to melanoma , 1999, Nature Genetics.

[8] Luigi Naldini,et al. Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo , 1997, Nature Biotechnology.