Nramp2 analysis in hemochromatosis probands

The mechanism that leads to iron overload in hereditary hemochromatosis is not yet fully understood and genes other than HFE may be involved. Nramp2 i s an intestinal iron transporter, upregulated by dietary iron deficiency, w hich also colocalizes with transferrin in recycling endosomes. The purpose of the present study was to analyze the coding region of the Nramp2 gene in 14 hemochromatosis probands which did not carry any HFE mutations on both chromosomes. We confirmed the existence of a polymorphism (1254 T --> C), w hich presumably is not associated with hereditary hemochromatosis, but we d id not find any mutation. On the other hand, we identified 17 splice varian ts of the Nramp2 mRNA. Eight corresponded to activation of cryptic splicing sequences between exons 3 and 4. They were observed in a majority of hemoc hromatosis probands and control subjects. This indicates the existence of a n important splicing instability in this region. At this stage, the biologi cal significance of these variants is unclear. Om study did not find eviden ce for the involvement of the Nramp2 gene in hereditary hemochromatosis. Th e remaining question is whether hemochromatosis probands in our study have iron overload because of environmental factors or due to mutation in gene(s ) other than HFE and Nramp2. (C) 2000 Academic Press.