| First Author | Mehaffey MG | Year | 2001 |
| Journal | Blood | Volume | 98 |
| Issue | 9 | Pages | 2681-8 |
| PubMed ID | 11675338 | Mgi Jnum | J:287089 |
| Mgi Id | MGI:6415189 | Doi | 10.1182/blood.v98.9.2681 |
| Citation | Mehaffey MG, et al. (2001) X-linked thrombocytopenia caused by a novel mutation of GATA-1. Blood 98(9):2681-8 |
| abstractText | A family with recessive X-linked thrombocytopenia affecting 4 males in 2 generations, characterized by macrothrombocytopenia, profound bleeding, and mild dyserythropoiesis, is described. Microsatellite linkage analysis identified a region of the X chromosome including the GATA-1 gene, which encodes a critical transcription factor involved in erythrocyte and megakaryocyte development. By sequencing the entire coding region of GATA-1, a 2-base mutation was detected that results in a single amino acid substitution (glycine 208 to serine) within a highly conserved portion of the N-terminal zinc finger domain. Restriction fragment length polymorphism confirmed that this novel mutation segregated with the affected males and female carrier. Although not required for DNA binding, Gly208 of GATA-1 is involved in direct interaction with Friend of GATA-1 (FOG), a cofactor required for normal megakaryocytic and erythroid development. These results demonstrate that the GATA-1-FOG interaction is partially disrupted by the mutation and that the greatest effect involves contact with the FOG zinc finger 9. These findings help describe a novel mutation of GATA-1 in humans as a cause of X-linked thrombocytopenia, and they confirm the vital role played by this transcription factor during in vivo megakaryocyte development. |
