Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1

Nat Genet. 2000 Mar;24(3):266-70. doi: 10.1038/73480.


Haematopoietic development is regulated by nuclear protein complexes that coordinate lineage-specific patterns of gene expression. Targeted mutagenesis in embryonic stem cells and mice has revealed roles for the X-linked gene Gata1 in erythrocyte and megakaryocyte differentiation. GATA-1 is the founding member of a family of DNA-binding proteins that recognize the motif WGATAR through a conserved multifunctional domain consisting of two C4-type zinc fingers. Here we describe a family with X-linked dyserythropoietic anaemia and thrombocytopenia due to a substitution of methionine for valine at amino acid 205 of GATA-1. This highly conserved valine is necessary for interaction of the amino-terminal zinc finger of GATA-1 with its essential cofactor, FOG-1 (for friend of GATA-1; refs 9-12). We show that the V205M mutation abrogates the interaction between Gata-1 and Fog-1, inhibiting the ability of Gata-1 to rescue erythroid differentiation in an erythroid cell line deficient for Gata-1 (G1E). Our findings underscore the importance of FOG-1:Gata-1 associations in both megakaryocyte and erythroid development, and suggest that other X-linked anaemias or thrombocytopenias may be caused by defects in GATA1.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Anemia, Dyserythropoietic, Congenital / genetics*
  • Child
  • Consensus Sequence
  • Cryptorchidism / genetics*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology
  • Erythroid-Specific DNA-Binding Factors
  • Female
  • GATA1 Transcription Factor
  • Hematopoiesis / genetics
  • Humans
  • Infant, Newborn
  • Male
  • Models, Molecular
  • Molecular Sequence Data
  • Pedigree
  • Point Mutation*
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / genetics
  • Thrombocytopenia / congenital
  • Thrombocytopenia / genetics*
  • Transcription Factors / chemistry
  • Transcription Factors / deficiency
  • Transcription Factors / genetics*
  • Transcription Factors / physiology
  • X Chromosome / genetics*
  • Zinc Fingers / genetics


  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • GATA1 protein, human
  • Recombinant Fusion Proteins
  • Transcription Factors