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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2618-2621. Prepublished online as a Blood First Edition Paper on December 5, 2006; DOI 10.1182/blood-2006-06-022848. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-06-022848v1 109/6/2618    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 Phillips, J. D. Articles by Kushner, J. P. Search for Related Content PubMed PubMed Citation Articles by Phillips, J. D. Articles by Kushner, J. P. Related Collections Hematopoiesis and Stem Cells Red Cells Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Congenital erythropoietic porphyria due to a mutation in GATA1: the first trans-acting mutation causative for a human porphyria John D. Phillips1, David P. Steensma2, Michael A. Pulsipher3, Gerald J. Spangrude1, and James P. Kushner1 1 Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT; 2 Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN; 3 Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT Congenital erythropoietic porphyria (CEP), an autosomal recessive disorder, is due to mutations of uroporphyrinogen III synthase (UROS). Deficiency of UROS results in excess uroporphyrin I, which causes photosensitization. We evaluated a 3-year-old boy with CEP. A hypochromic, microcytic anemia was present from birth, and platelet counts averaged 70 x 109/L (70 000/µL). Erythrocyte UROS activity was 21% of controls. Red cell morphology and globin chain labeling studies were compatible with ß-thalassemia. Hb electrophoresis revealed 36.3% A, 2.4% A2, 59.5% F, and 1.8% of an unidentified peak. No UROS or - and ß-globin mutations were found in the child or the parents. The molecular basis of the phenotype proved to be a mutation of GATA1, an X-linked transcription factor common to globin genes and heme biosynthetic enzymes in erythrocytes. A mutation at codon 216 in the child and on one allele of his mother changed arginine to tryptophan (R216W). This is the first report of a human porphyria due to a mutation in a trans-acting factor and the first association of CEP with thalassemia and thrombocytopenia. The Hb F level of 59.5% suggests a role for GATA-1 in globin switching. A bone marrow allograft corrected both the porphyria and the thalassemia. 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] K. E. Elagib, I. S. Mihaylov, L. L. Delehanty, G. C. Bullock, K. D. Ouma, J. F. Caronia, S. L. Gonias, and A. N. Goldfarb Cross-talk of GATA-1 and P-TEFb in megakaryocyte differentiation Blood, December 15, 2008; 112(13): 4884 - 4894. [Abstract] [Full Text] [PDF] J. S. Caudill, H. Imran, J. C. Porcher, and D. P. Steensma Congenital sideroblastic anemia associated with germline polymorphisms reducing expression of FECH Haematologica, October 1, 2008; 93(10): 1582 - 1584. [Full Text] [PDF] M. Kobayashi and M. Yamamoto Regulation of GATA1 Gene Expression J. Biochem., July 1, 2007; 142(1): 1 - 10. [Abstract] [Full Text] [PDF]

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