Abstract |
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 10(9)/L (70,000/microL). Erythrocyte UROS activity was 21% of controls. Red cell morphology and globin chain labeling studies were compatible with beta-thalassemia. Hb electrophoresis revealed 36.3% A, 2.4% A(2), 59.5% F, and 1.8% of an unidentified peak. No UROS or alpha- and beta-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.
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Authors | John D Phillips, David P Steensma, Michael A Pulsipher, Gerald J Spangrude, James P Kushner |
Journal | Blood
(Blood)
Vol. 109
Issue 6
Pg. 2618-21
(Mar 15 2007)
ISSN: 0006-4971 [Print] United States |
PMID | 17148589
(Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- GATA1 Transcription Factor
- GATA1 protein, human
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Topics |
- Amino Acid Sequence
- Child, Preschool
- Female
- GATA1 Transcription Factor
(chemistry, genetics)
- Humans
- Male
- Molecular Sequence Data
- Mutation
(genetics)
- Pedigree
- Porphyria, Erythropoietic
(etiology, genetics, pathology)
- Protein Binding
- Transcriptional Activation
(genetics)
- Zinc Fingers
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