title: Nramp2 analysis in hemochromatosis probands.
abstract: The mechanism that leads to iron overload in hereditary hemochromatosis is not yet fully understood and genes other than HFE may be involved. Nramp2 is an intestinal iron transporter, upregulated by dietary iron deficiency, which 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), which presumably is not associated with hereditary hemochromatosis, but we did not find any mutation. On the other hand, we identified 17 splice variants of the Nramp2 mRNA. Eight corresponded to activation of cryptic splicing sequences between exons 3 and 4. They were observed in a majority of hemochromatosis probands and control subjects. This indicates the existence of an important splicing instability in this region. At this stage, the biological significance of these variants is unclear. Our study did not find evidence for the involvement of the Nramp2 gene in hereditary hemochromatosis. The 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.
authors.affiliation: Etablissement Français du Sang-Bretagne, site de Brest, France. gerald.legac@univ-brest.fr
authors.forename: G
authors.initials: G
authors.lastname: Le Gac
authors.forename: C
authors.initials: C
authors.lastname: Mura
authors.forename: O
authors.initials: O
authors.lastname: Raguenes
authors.forename: A Y
authors.initials: AY
authors.lastname: Mercier
authors.forename: M
authors.initials: M
authors.lastname: de Braekeleer
authors.forename: C
authors.initials: C
authors.lastname: Férec
mesh_terms: D017398:Alternative Splicing; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005260:Female; D006432:Hemochromatosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D033862:Iron-Binding Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D018076:DNA, Complementary; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2