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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 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 Citation Map 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. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Microcytic anemia and hepatic iron overload in a child with compound heterozygous mutations in DMT1 (SCL11A2) Achille Iolascon, Maria d'Apolito, Veronica Servedio, Flora Cimmino, Antonio Piga, and Clara Camaschella From the Genetica Medica, Dipartimento di Biochimica e Biotecnologie Mediche, Università Federico II, Naples; Ceinge Advanced Biotechnologies, Naples; Laboratorio di Medicina Molecolare, Dipartimento di Scienze Mediche e del Lavoro, Università degli Studi Foggia, Foggia; Dipartimento di Pediatria, Università di Torino, Turin; and Università Vita-Salute, Istituto Scientifico San Raffaele, Milan, Italy. 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 and defective intestinal iron use and erythroid iron use. We report the hematologic phenotype of a child, compound heterozygote for 2 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 analysis. The proband required blood transfusions until erythropoietin treatment allowed transfusion independence when hemoglobin levels between 75 and 95 g/L (7.5 and 9.5 g/dL) were achieved. Hematologic 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 the up-regulation of other pathways of iron use. 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] M. A. Melis, M. Cau, R. Congiu, G. Sole, S. Barella, A. Cao, M. Westerman, M. Cazzola, and R. Galanello A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron Haematologica, October 1, 2008; 93(10): 1473 - 1479. [Abstract] [Full Text] [PDF] F. Guillem, S. Lawson, C. Kannengiesser, M. Westerman, C. Beaumont, and B. Grandchamp Two nonsense mutations in the TMPRSS6 gene in a patient with microcytic anemia and iron deficiency Blood, September 1, 2008; 112(5): 2089 - 2091. [Abstract] [Full Text] [PDF] N. C. Andrews Forging a field: the golden age of iron biology Blood, July 15, 2008; 112(2): 219 - 230. [Full Text] [PDF] C. Camaschella, A. Campanella, L. De Falco, L. Boschetto, R. Merlini, L. Silvestri, S. Levi, and A. Iolascon The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload Blood, August 15, 2007; 110(4): 1353 - 1358. [Abstract] [Full Text] [PDF] K. Thompson, R. M. Molina, J. D. Brain, and M. Wessling-Resnick Belgrade Rats Display Liver Iron Loading J. Nutr., December 1, 2006; 136(12): 3010 - 3014. [Abstract] [Full Text] [PDF] S. Lam-Yuk-Tseung, V. Picard, and P. Gros Identification of a Tyrosine-based Motif (YGSI) in the Amino Terminus of Nramp1 (Slc11a1) That Is Important for Lysosomal Targeting J. Biol. 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