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Blood, 1 January 2006, Vol. 107, No. 1, pp. 349-354. Prepublished online as a Blood First Edition Paper on September 13, 2005; DOI 10.1182/blood-2005-06-2477. This Article Full Text (PDF) All Versions of this Article: 2005-06-2477v1 107/1/349    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Iolascon, A. Articles by Camaschella, C. Search for Related Content PubMed PubMed Citation Articles by Iolascon, A. Articles by Camaschella, C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 23, 2005 Accepted August 26, 2005 Microcytic anemia and hepatic iron overload in a child with compound heterozygous mutations in DMT1 Achille Iolascon*, Maria d'Apolito, Veronica Servedio, Flora Cimmino, Antonio Piga, and Clara Camaschella Genetica Medica, Dip. di Biochimica e Biotecnologie Mediche, Universita Federico II and CEINGE Advanced Biotechnologies, Napoli, Italy Laboratorio di Medicina Molecolare, Dip. Di Scienze Mediche e del Lavoro, Universita degli Studi Foggia, Foggia, Foggia, Italy Dipartimento di Pediatria, Universita di Torino, Torino, Italy Universita Vita-Salute, Istituto Scientifico San Raffaele, Milano, Italy * Corresponding author; email: iolascon{at}dbbm.unina.it. Divalent metal transporter 1 (DMT1) mediates apical iron uptake in duodenal enterocytes and iron transfer from the transferrin receptor endosomal cycle into the cytosol in erythroid cells. Both mk mice and Belgrade rats, which carry an identical DMT1 mutation, exhibit severe microcytic anemia at birth, defective intestinal iron absorption and erythroid iron utilization. We report the hematological phenotype of a child, compound heterozygote for two DMT1 mutations, who was affected by severe anemia since birth and showed hepatic iron overload. The novel mutations were a 3 bp deletion in intron 4 (c.310 - 3_5del CTT) resulting in a splicing abnormality and a C >T transition at nucleotide 1246(p. R416C). A striking reduction of DMT1 protein in peripheral blood mononuclear cells was demonstrated by western blot. The proband required blood transfusions until erythropoietin treatment allowed transfusion-independence with haemoglobin levels between 7.5-9.5 g/dL. Hematological data of this patient at birth and in the first years of life strengthen the essential role of DMT1 in erythropoiesis. The early onset of iron overload indicates that, as in animal models, DMT1 is dispensable for liver iron uptake, whereas its deficiency in the gut is likely bypassed by upregulation of other pathways of iron absorption. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Iolascon, L. De Falco, and C. Beaumont Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis Haematologica, March 1, 2009; 94(3): 395 - 408. [Abstract] [Full Text] [PDF] N. J. Foot, H. E. Dalton, L. M. Shearwin-Whyatt, L. Dorstyn, S.-S. Tan, B. Yang, and S. Kumar Regulation of the divalent metal ion transporter DMT1 and iron homeostasis by a ubiquitin-dependent mechanism involving Ndfips and WWP2 Blood, November 15, 2008; 112(10): 4268 - 4275. [Abstract] [Full Text] [PDF] M. A. Melis, M. Cau, R. Congiu, G. Sole, S. Barella, A. Cao, M. Westerman, M. Cazzola, and R. 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