title: Effects of the R216Q mutation of GATA-1 on erythropoiesis and megakaryocytopoiesis.
abstract: 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.
authors.affiliation: Clinica Medica III, IRCCS Policlinico, San Matteo University, piazzale Golgi 27100 Pavia, Italy. c.balduini@smatteo.pv.it
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Balduini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pecci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Loffredo
authors.forename: Paola
authors.initials: P
authors.lastname: Izzo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Noris
authors.forename: Michela
authors.initials: M
authors.lastname: Grosso
authors.forename: Gaetano
authors.initials: G
authors.lastname: Bergamaschi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Rosti
authors.forename: Umberto
authors.initials: U
authors.lastname: Magrini
authors.forename: Iride F
authors.initials: IF
authors.lastname: Ceresa
authors.forename: Valeria
authors.initials: V
authors.lastname: Conti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Poggi
authors.forename: Anna
authors.initials: A
authors.lastname: Savoia
mesh_terms: 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
chemical_list: 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