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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2770-2771. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Balduini, C. L. Articles by Savoia, A. Search for Related Content PubMed PubMed Citation Articles by Balduini, C. L. Articles by Savoia, A. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CORRESPONDENCE Why the disorder induced by GATA1 Arg216Gln mutation should be called "X-linked thrombocytopenia with thalassemia" rather than "X-linked gray platelet syndrome" To the editor: GATA1 mutations induce 2 X-linked thrombocytopenias: dyserythropoietic anemia with thrombocytopenia (Online Mendelian Inheritance in Man [OMIM] 300367 [OMIM] ) and X-linked thrombocytopenia with thalassemia (XLTT; OMIM314050). The former has been described in 6 families with 5 different GATA1 mutations,1,2 whereas the latter has been identified in 3 pedigrees with the 216R>Q substitution.3–5 In both illnesses, patients present mild dyserythropoiesis, red cell hemolysis, severely defective maturation of megakaryocytes, macrothrombocytopenia with -granule deficiency, and abnormalities of the cytoplasmic membrane system. Unbalanced globin-chain synthesis resembling ß-thalassemia has been described only in patients with XLTT, whereas severe anemia and thrombocytopenia have only been observed in dyserythropoietic anemia with thrombocytopenia. These 2 disorders are therefore closely related and are the unique inherited thrombocytopenias that constitutively present abnormalities of red cell line. Tubman et al6 identified a family with X-linked thrombocytopenia, large agranular platelets, and increased erythrocyte hemoglobin F (HbF) deriving from the 216R>Q mutation in GATA1 and recently reported it in this journal under the title "X-linked gray platelet syndrome due to a GATA1 216R>Q mutation." Because genotype and phenotype of this pedigree are completely superimposable with those observed in previous patients with XLTT, their decision to classify them as "X-linked gray platelet syndrome" risks producing further confusion in the field of inherited thrombocytopenias, which is already per se complex and confusing. It is perfectly true that the large platelets with -granule deficiency observed in XLTT are in some respects similar to those typical of Gray platelet syndrome7 (GPS; OMIM 139090 [OMIM] ), but it is also unquestionable that several other findings differentiate the former from the latter. For instance, the red cell defect of XLTT has never been described in GPS, whereas the bone marrow emperipolesis of GPS8,9 is not present in XLTT. Moreover, different expression and localization of -granule proteins, such as differences in the spectrum of functional defects of platelets, distinguish these 2 disorders. Finally, the gene responsible for the classical GPS has not yet been identified, and it may be everywhere except in chromosome X, because an X-linked transmission has been never observed, whereas autosomal dominant inheritance has been well documented in some pedigrees. So GPS and XLTT are different disorders presenting the common finding of large platelets with -granule deficiency. Furthermore, applying the term GPS to all conditions with pale platelets due to severe -granule deficiency would also imply that other genetic thrombocytopenias with this finding (Medich giant platelet disorder, white platelet syndrome) have to be considered GPS. On the contrary, some affected members of GPS pedigrees who, due to the variable penetrance of this disorder, have very mild -granule deficiency (despite full expression of other platelet defects)9 could no longer be classified as GPS. So, to avoid confusion, we suggest that (1) the disorder deriving from GATA1 216R>Q mutation is not an "X-linked gray platelet syndrome" but rather XLTT, and (2) the term GPS should be used to indicate the illness (or the syndrome) that several reports and reviews7 have well described in the past. Authorship Conflict-of-interest disclosure: The authors declare no competing financial interests. Correspondence: Carlo L. Balduini, Clinica Medica III, Fondazione IRCCS Policlinico San Matteo, piazzale Golgi, 27100 Pavia, Italy; e-mail: c.balduini{at}smatteo.pv.it. Carlo L. Balduini, Erica De Candia, and Anna Savoia References Balduini CL and Savoia A. Inherited thrombocytopenias: molecular mechanisms. Semin Thromb Hemost 2004; 30:513–523.[CrossRef][Medline] [Order article via Infotrieve] Del Vecchio GC, Giordani L, De Santis A, De Mattia D. Dyserythropoietic anemia and thrombocytopenia due to a novel mutation in GATA-1. Acta Haematol 2005; 114:113–116.[CrossRef][Medline] [Order article via Infotrieve] Yu C, Niakan KK, Matsushita M, Stamatoyannopoulos Orkin SH, Raskind W. X-linked thrombocytopenia with thalassemia due to a mutation in the amino-finger of GATA-1 affecting DNA-binding rather than FOG-1 interaction. Blood 2002; 100:2040–2045.[Abstract/Free Full Text] Balduini CL, Pecci A, Loffredo G, et al. Effects of the R216Q mutation of GATA-1 on erythropoiesis and megakaryocytopoiesis. Thromb Haemost 2004; 91:129–140.[Medline] [Order article via Infotrieve] Hughan SC, Senis Y, Best D, et al. Selective impairment of platelet activation to collagen in the absence of GATA1. Blood 2005; 105:4369–4376.[Abstract/Free Full Text] Tubman VN, Levine JE, Campagna DR, et al. X-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation. Blood 2007; 109:3297–3299.[Abstract/Free Full Text] Nurden AT and Nurden P. The gray platelet syndrome: clinical spectrum of the disease. Blood Rev 2007; 21:21–36.[CrossRef][Medline] [Order article via Infotrieve] Falik-Zaccai TC, Anikster Y, Rivera CE, et al. A new genetic isolate of gray platelet syndrome (GPS): clinical, cellular, and hematologic characteristics. Mol Genet Metab 2001; 74:303–313.[CrossRef][Medline] [Order article via Infotrieve] De Candia E, Pecci A, Ciabattoni G, et al. Defective platelet responsiveness to thrombin and protease-activated receptors agonists in a novel case of gray platelet syndrome: correlation between the platelet defect and the alpha-granule content in the patient and four relatives. J Thromb Haemost 2007; 5:551–559.[CrossRef][Medline] [Order article via Infotrieve] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Response: What's in a name? Ellis J. Neufeld, Venee N. Tubman, Jason E. Levine, Dean R. Campagna, Rita Monahan-Earley, Ann M. Dvorak, and Mark D. Fleming Blood 2007 110: 2771. [Full Text] [PDF] X-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation Venée N. Tubman, Jason E. Levine, Dean R. Campagna, Rita Monahan-Earley, Ann M. Dvorak, Ellis J. Neufeld, and Mark D. Fleming Blood 2007 109: 3297-3299. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Balduini, C. L. Articles by Savoia, A. Search for Related Content PubMed PubMed Citation Articles by Balduini, C. L. Articles by Savoia, A. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?

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