title: Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload.
abstract: DMT1 mediates the pH-dependent uptake of Fe(2+) from the diet in duodenal enterocytes and in most other cells. It transfers iron from the endosomes to the cytosol following the uptake of the transferrin-transferrin receptor complex. DMT1 mutations are responsible for severe hypochromic microcytic anemia in rodents and in 2 human patients described recently. We report a compound heterozygote for 2 new DMT1 mutations, associated with microcytic anemia from birth and progressive liver iron overload. The first mutation is a GTG deletion in exon 5, leading to the V114 in-frame deletion in transmembrane domain 2, and the second is a G --> T substitution in exon 8 leading to the G212V replacement in transmembrane domain 5. Together with the 2 previously reported cases, this patient defines a new syndrome of congenital microcytic hypochromic anemia, poorly responsive to oral iron treatment, with liver iron overload associated paradoxically with normal to moderately elevated serum ferritin levels.
authors.affiliation: INSERM U773, Centre de Recherche Biomédicale Bichat Beaujon CRB3, BP 416, 16 rue Henri Huchard, F-75018 Paris, France. beaumont@bichat.inserm.fr
authors.forename: Carole
authors.initials: C
authors.lastname: Beaumont
authors.forename: Jean
authors.initials: J
authors.lastname: Delaunay
authors.forename: Gilles
authors.initials: G
authors.lastname: Hetet
authors.forename: Bernard
authors.initials: B
authors.lastname: Grandchamp
authors.forename: Mariane
authors.initials: M
authors.lastname: de Montalembert
authors.forename: Gil
authors.initials: G
authors.lastname: Tchernia
mesh_terms: D000595:Amino Acid Sequence; D000740:Anemia / Q000235:genetics*; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics*; D002648:Child; D017124:Conserved Sequence; D005260:Female; D005293:Ferritins / Q000097:blood* / Q000172:deficiency*; D006801:Humans; D019190:Iron Overload / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D005293:Ferritins; D000099236:Solute Carrier Family 11, Member 2