X-linked thrombocytopenia with thalassemia maps to a mutation (Arg216Gln) in GATA-1.

(A) Pedigree of a family with X-linked thrombocytopenia with thalassemia.15,16 Black squares represent affected males; circles with black discs represent obligate carrier females. Differences in GATA-1 DNA sequence at codon 216 are indicated below individuals: CGG (arginine, wild-type); CAG (glutamine, mutant). Patients who were evaluated for α-globin/β-globin chain imbalance15,16 are designated with + (elevated α/β ratio) or − (within normal limits). (B) Partial sequence of the N finger of GATA-1. Arg216 is conserved across GATA-1 orthologs of various species. Here, amino acid numbering relates to the human, rat, and mouse polypeptides. Val205, mutated to methionine in familial dyserythropoietic anemia with thrombocytopenia,14 is also highlighted here. Polypeptide sequences are shown as single-letter code. (C) The N finger of GATA-1 has 2 faces, a FOG face and a DNA face.10,12 Approximate division of these faces is superimposed on the NMR structure.12 Val205 (green) is highlighted on the FOG face, and Arg216 (blue) is highlighted on the DNA face.