Effects of the R216Q mutation of GATA-1 on erythropoiesis and megakaryocytopoiesis.
The transcription factor GATA-1, together with its cofactor FOG-1, regulates erythropoiesis and megakaryocytopoiesis. Mutations in the DNA or FOG-1 binding sites of its N-terminal zinc finger result in different illnesses. Alterations of the FOG-1 face are responsible for dyserythropoietic anemia with thrombocytopenia while R216Q, the only mutation identified in the DNA face, induces X-linked thrombocytopenia with thalassemia (XLTT). The former disorder has been studied in detail whereas little is known about the latter since only one family has been investigated. We studied a second family with an R216Q, showing that XLTT and dyserythropoietic anemia with thrombocytopenia, even if different clinical entities, are closely related disorders. In both cases, patients present mild dyserythropoiesis, red cell hemolysis, severely defective maturation of megakaryocytes, macrothrombocytopenia with alpha-granule deficiency, and abnormalities of the cytoplasmic membrane system. However, a thalassemia minor phenotype has only been described in patients with XLTT whereas severe anemia and thrombocytopenia with evident defects of platelet composition and function may be observed only in dyserythropoietic anemia with thrombocytopenia.
Balduini
Carlo L
CL
Clinica Medica III, IRCCS Policlinico, San Matteo University, piazzale Golgi 27100 Pavia, Italy. c.balduini@smatteo.pv.it
Pecci
Alessandro
A
Loffredo
Giuseppe
G
Izzo
Paola
P
Noris
Patrizia
P
Grosso
Michela
M
Bergamaschi
Gaetano
G
Rosti
Vittorio
V
Magrini
Umberto
U
Ceresa
Iride F
IF
Conti
Valeria
V
Poggi
Vincenzo
V
Savoia
Anna
A
D001665:Binding Sites; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D002648:Child; D041321:Chromosomes, Human, X / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D050981:Erythroid-Specific DNA-Binding Factors; D004920:Erythropoiesis / Q000235:genetics*; D005192:Family Health; D005260:Female; D005434:Flow Cytometry; D050982:GATA1 Transcription Factor; D008040:Genetic Linkage; D005914:Globins / Q000737:chemistry; D006461:Hemolysis; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000378:metabolism; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013789:Thalassemia / Q000235:genetics; D013921:Thrombocytopenia / Q000235:genetics; D034061:Thrombopoiesis / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D010980:Platelet Membrane Glycoproteins; D014157:Transcription Factors; D005914:Globins; D004247:DNA