Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload.
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.
Beaumont
Carole
C
INSERM U773, Centre de Recherche Biomédicale Bichat Beaujon CRB3, BP 416, 16 rue Henri Huchard, F-75018 Paris, France. beaumont@bichat.inserm.fr
Delaunay
Jean
J
Hetet
Gilles
G
Grandchamp
Bernard
B
de Montalembert
Mariane
M
Tchernia
Gil
G
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
D027682:Cation Transport Proteins; D005293:Ferritins; D000099236:Solute Carrier Family 11, Member 2