Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA 1

Kim E. Nichols, John D. Crispino, Mortimer Poncz, James G. White, Stuart H. Orkin, John M. Maris, Mitchell J. Weiss*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

234 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)266-270
Number of pages5
JournalNature Genetics
Issue number3
StatePublished - Mar 2000

ASJC Scopus subject areas

  • Genetics


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