title: Dyserythropoietic anemia and thrombocytopenia due to a novel mutation in GATA-1.
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.
authors.affiliation: Department of Biomedicine of Evolutive Age, University of Bari, Bari, Italy.
authors.forename: Giovanni Carlo
authors.initials: GC
authors.lastname: Del Vecchio
authors.forename: Lucia
authors.initials: L
authors.lastname: Giordani
authors.forename: Attilio
authors.initials: A
authors.lastname: De Santis
authors.forename: Domenico
authors.initials: D
authors.lastname: De Mattia
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D000740:Anemia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D001120:Arginine / Q000235:genetics; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D050981:Erythroid-Specific DNA-Binding Factors; D004920:Erythropoiesis / Q000235:genetics; D005260:Female; D050982:GATA1 Transcription Factor; D005998:Glycine / Q000235:genetics; D006801:Humans; D008533:Megakaryocytes / Q000473:pathology; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D013921:Thrombocytopenia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D034061:Thrombopoiesis / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D014157:Transcription Factors; D001120:Arginine; D005998:Glycine