Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload

• Published in: Blood Vol. 107; no. 10; pp. 4168 - 4170
• Main Authors: Beaumont, Carole, Delaunay, Jean, Hetet, Gilles, Grandchamp, Bernard, de Montalembert, Mariane, Tchernia, Gil
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.05.2006; The Americain Society of Hematology
• Subjects: Amino Acid Sequence; Anemia - genetics; Anemias. Hemoglobinopathies; Animals; Biological and medical sciences; Cation Transport Proteins - genetics; Child; Conserved Sequence; Diseases of red blood cells; Female; Ferritins - blood; Ferritins - deficiency; Hematologic and hematopoietic diseases; Humans; Iron Overload - genetics; Liver - metabolism; Male; Medical sciences; Molecular Sequence Data; Mutation; Pedigree; Sequence Alignment; Sequence Homology, Amino Acid; Human; Microcytic anemia; Hypochromia; Digestive system; Liver; Divalent metal transporter 1; Ferritin; Iron; Gene; Overload; Animal; Genetics; Mutation; Intestinal absorption
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-10-4269

DMT1 mediates the pH-dependent uptake of Fe2+ 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 transferrintransferrin 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.