Dyserythropoietic Anemia and Thrombocytopenia due to a Novel Mutation in GATA-1
- 1 August 2005
- journal article
- Published by S. Karger AG in Acta Haematologica
- Vol. 114 (2) , 113-116
- https://doi.org/10.1159/000086586
Abstract
Hematopoiesis is a complex process regulated by nuclear proteins that coordinate lineage-specific patterns of gene expression. Targeted mutagenesis has revealed critical roles for the X-linked transcription factor GATA-1 in erythrocyte and megakaryocyte differentiation. GATA-1 has two zinc fingers essential for normal function. The C-terminal finger is necessary for DNA binding. The N-terminal finger mediates interaction with FOG-1, a cofactor for GATA-1. Mutations in the N-terminal zinc finger of GATA-1 result in abnormal hematopoiesis. Here we report a family with a novel single base mutation that results in an amino acid substitution (Gly208Arg) within the highly conserved portion of the GATA-1 N-terminal finger domain, leading to dyserythropoietic anemia and macrothrombocytopenia. Another mutation described at the same codon (208) has been found to be associated with thrombocytopenia only. Our data support and extend the effect of the amino acid substitution at codon 208 on GATA-1 function not only regarding megakaryocyte but also regarding erythroid development.Keywords
This publication has 16 references indexed in Scilit:
- X-linked thrombocytopenia with thalassemia from a mutation in the amino finger of GATA-1 affecting DNA binding rather than FOG-1 interactionBlood, 2002
- Different substitutions at residue D218 of the X-linked transcription factor GATA1 lead to altered clinical severity of macrothrombocytopenia and anemia and are associated with variable skewed X inactivation.Human Molecular Genetics, 2002
- Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1Nature Genetics, 2000
- Use of Altered Specificity Mutants to Probe a Specific Protein–Protein Interaction in DifferentiationMolecular Cell, 1999
- Key Residues Characteristic of GATA N-fingers Are Recognized By FOGPublished by Elsevier ,1998
- A lineage-selective knockout establishes the critical role of transcription factor GATA-1 in megakaryocyte growth and platelet developmentThe EMBO Journal, 1997
- Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1.Proceedings of the National Academy of Sciences, 1996
- Distinct roles for the two cGATA-1 finger domains.Molecular and Cellular Biology, 1992
- The erythroid-specific transcription factor eryf1: A new finger proteinCell, 1989
- Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cellsNature, 1989