Congenital erythropoietic porphyria due to a mutation in GATA1: the first trans-acting mutation causative for a human porphyria.

• 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.
• Authors: John D Phillips, David P Steensma, Michael A Pulsipher, Gerald J Spangrude, James P Kushner (Affiliation: Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. john.phillips at hsc.utah.edu)
• 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)

Chemical References

• GATA1 Transcription Factor
• GATA1 protein, human

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