Effects of the R216Q mutation of GATA-1 on erythropoiesis and megakaryocytopoiesis

Carlo L. Balduini; Alessandro Pecci; Giuseppe Loffredo; Paola Izzo; Patrizia Noris; Michela Grosso; Gaetano Bergamaschi; Vittorio Rosti; Umberto Magrini; Iride F. Ceresa; Valeria Conti; Vincenzo Poggi; Anna Savoia

doi:10.1160/TH03-05-0290

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 91(01): 129-140
DOI: 10.1160/TH03-05-0290

Platelets and Blood Cells

Schattauer GmbH

Effects of the R216Q mutation of GATA-1 on erythropoiesis and megakaryocytopoiesis

Carlo L. Balduini

¹IRCCS Policlinico San Matteo-University of Pavia, Italy

,

Alessandro Pecci

¹IRCCS Policlinico San Matteo-University of Pavia, Italy

,

Giuseppe Loffredo

²Pausilipon Hospital, Naples, Italy

,

Paola Izzo

³University Federico II and CEINGE-Biotecnologie Avanzate, Naples, Italy

,

Patrizia Noris

¹IRCCS Policlinico San Matteo-University of Pavia, Italy

,

Michela Grosso

³University Federico II and CEINGE-Biotecnologie Avanzate, Naples, Italy

,

Gaetano Bergamaschi

¹IRCCS Policlinico San Matteo-University of Pavia, Italy

,

Vittorio Rosti

¹IRCCS Policlinico San Matteo-University of Pavia, Italy

,

Umberto Magrini

¹IRCCS Policlinico San Matteo-University of Pavia, Italy

,

Iride F. Ceresa

¹IRCCS Policlinico San Matteo-University of Pavia, Italy

,

Valeria Conti

⁴Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy

,

Vincenzo Poggi

²Pausilipon Hospital, Naples, Italy

,

Anna Savoia

⁴Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy

› Author Affiliations

Abstract

Summary

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 α-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.

Keywords

GATA-1 - thrombocytopenia - thalassemia - platelets - megakaryocytes

Full Text

References

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