Effects of the R216Q mutation of GATA-1 on erythropoiesis and megakaryocytopoiesis (original) (raw)

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

Platelets and Blood Cells

Schattauer GmbH

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 AffiliationsFinancial support: This work was supported by the Italian Telethon Foundation (grants GP0019/01 to C.L.B. and TIGEM 2000-2003 to A.S.), the Italian Ministry of University and Scientific Research (C.L.B.) and the Italian Ministry of Health (C.L.B. and A.S.).

Further Information

Publication History

Received 14 May 2003

Accepted after revision 18 September 2003

Publication Date:
30 November 2017 (online)

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

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