Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Congenital transfusion-dependent anemia and thrombocytopenia with myelodysplasia due to a recurrent GATA1G208R germline mutation

Leukemia volume 22, pages 432–434 (2008)Cite this article

The X-linked gene GATA1 encodes a 414-amino-acid hematopoietic transcription factor that controls erythroid and megakaryocytic differentiation. Virtually all cases of transient myeloproliferative disease and acute megakaryoblastic leukemia in children with Down syndrome harbor somatic GATA1 mutations typically affecting exon 2 and leading to expression of the short isoform, GATA-1s, which lacks the transcriptional activation domain. Moreover, germline missense mutations in exon 4 of GATA1 that predict alterations of amino acids Val205, Gly208, Arg216 or Asp218 of the N-terminal zinc-finger domain (residues 204–228) have been reported in nine families.1, 2, 3, 4, 5, 6, 7, 8, 9 One additional family has been found to harbor a germline mutation, GATA1 c.322G>C, which leads to expression of GATA-1s.10 Consistent with X-linked inheritance and full penetrance, germline GATA1 mutations disrupt hematopoiesis in males who harbor a hemizygous mutant GATA1 allele. In contrast, female heterozygous carriers have no or minor hematopoietic defects such as mild chronic thrombocytopenia.1, 2, 3, 4, 5, 6, 7, 8, 9, 10 The spectrum of abnormalities caused by different GATA1 mutations probably depends on the function of the predicted mutant protein such as the ability to associate with cofactor FOG-1.9 Hematologic abnormalities include dyserythropoietic anemia and thrombocythemia (V205M, G208R, D218Y and GATA-1s),1, 3, 9, 10 thrombocytopenia with mild dyserythropoiesis (D218G, G208S),2, 8 thrombocytopenia with thalassemia (R216Q),4, 5 congenital erythropoietic porphyria (R216W),7 and gray platelet syndrome (R216Q).6 Splenomegaly is noted in some cases5, 7 and is likely to be due to ineffective and consecutive extramedullary hematopoiesis. To date, only the GATA1R216Q mutation has been identified in more than one family,4, 5, 6 hampering phenotype–genotype correlation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Nichols KE, Crispino JD, Poncz M, White JG, Orkin SH, Maris JM et al. Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1. Nat Genet 2000; 24: 266–270.

    Article  CAS  Google Scholar 

  2. Mehaffey MG, Newton AL, Gandhi MJ, Crossley M, Drachman JG . X-linked thrombocytopenia caused by a novel mutation of GATA-1. Blood 2001; 98: 2681–2688.

    Article  CAS  Google Scholar 

  3. 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.

    Article  Google Scholar 

  4. Yu C, Niakan KK, Matsushita M, Stamatoyannopoulos G, Orkin SH, Raskind WH . X-linked thrombocytopenia with thalassemia from a mutation in the amino finger of GATA-1 affecting DNA binding rather than FOG-1 interaction. Blood 2002; 100: 2040–2045.

    Article  CAS  Google Scholar 

  5. Balduini CL, Pecci A, Loffredo G, Izzo P, Noris P, Grosso M et al. Effects of the R216Q mutation of GATA-1 on erythropoiesis and megakaryocytopoiesis. Thromb Haemost 2004; 91: 129–140.

    Article  CAS  Google Scholar 

  6. Tubman VN, Levine JE, Campagna DR, Monahan-Earley R, Dvorak AM, Neufeld EJ et al. X-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation. Blood 2007; 109: 3297–3299.

    Article  CAS  Google Scholar 

  7. Phillips JD, Steensma DP, Pulsipher MA, Spangrude GJ, Kushner JP . Congenital erythropoietic porphyria due to a mutation in GATA1: the first trans-acting mutation causative for a human porphyria. Blood 2007; 109: 2618–2621.

    Article  CAS  Google Scholar 

  8. Freson K, Devriendt K, Matthijs G, Van Hoof A, De Vos R, Thys C et al. Platelet characteristics in patients with X-linked macrothrombocytopenia because of a novel GATA1 mutation. Blood 2001; 98: 85–92.

    Article  CAS  Google Scholar 

  9. Freson K, Matthijs G, Thys C, Marien P, Hoylaerts MF, Vermylen J et al. Different substitutions at residue D218 of the X-linked transcription factor GATA1 lead to altered clinical severity of macrothrombocytopenia and anemia and are associated with variable skewed X inactivation. Hum Mol Genet 2002; 11: 147–152.

    Article  CAS  Google Scholar 

  10. Hollanda LM, Lima CS, Cunha AF, Albuquerque DM, Vassallo J, Ozelo MC et al. An inherited mutation leading to production of only the short isoform of GATA-1 is associated with impaired erythropoiesis. Nat Genet 2006; 38: 807–812.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Cornelia Klein for technical assistance.

Author information

Authors and Affiliations

  1. Department of Pediatrics and Adolescent Medicine, Pediatric Hematology/Oncology, University of Freiburg, Freiburg, Germany

    C P Kratz, C M Niemeyer, A Karow & B Strahm

  2. Krankenhaus Barmherzige Brüder Regensburg, Klinik St Hedwig/Pädiatrische Onkologie und Hämatologie, Regensburg, Germany

    M Volz-Fleckenstein

  3. Department of Pathology, University of Freiburg, Freiburg, Germany. E-mail: christian.kratz@uniklinik-freiburg.de,

    A Schmitt-Gräff

Authors
  1. C P Kratz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C M Niemeyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Karow
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Volz-Fleckenstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Schmitt-Gräff
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B Strahm
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kratz, C., Niemeyer, C., Karow, A. et al. Congenital transfusion-dependent anemia and thrombocytopenia with myelodysplasia due to a recurrent GATA1G208R germline mutation. Leukemia 22, 432–434 (2008). https://doi.org/10.1038/sj.leu.2404904

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404904

This article is cited by

Search

Advanced search

Quick links