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Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome)

Nature Genetics volume 43, pages 929–931 (2011)Cite this article

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Abstract

We report an allelic series of eight mutations in GATA2 underlying Emberger syndrome, an autosomal dominant primary lymphedema associated with a predisposition to acute myeloid leukemia. GATA2 is a transcription factor that plays an essential role in gene regulation during vascular development and hematopoietic differentiation. Our findings indicate that haploinsufficiency of GATA2 underlies primary lymphedema and predisposes to acute myeloid leukemia in this syndrome.

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Figure 1: Clinical and genetic findings in Emberger syndrome.

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Acknowledgements

This study has been made possible by the commitment and courage of the families concerned, and we are indebted to them. This work was supported by the British Heart Foundation (BHF) grants RG/08/006/25302, PG/10/58/28477 and FS/06/063/21445. The authors also acknowledge support from the Department of Health through the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. This research utilized the resources of the Biomics Unit at St George's University of London. We also thank T. Enver, University College London Cancer Institute, London for kindly providing the GATA2 reporter constructs.

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Author notes

  1. Pia Ostergaard and Michael A Simpson: These authors contributed equally to this work.

Authors and Affiliations

  1. Medical Genetics Unit, Biomedical Sciences, St. George's University of London, London, UK

    Pia Ostergaard & Steve Jeffery

  2. Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London, UK

    Michael A Simpson, Wesley J Woollard, Dimitra Dafou & Richard C Trembath

  3. Clinical Genetics, Guy's and St. Thomas' National Health Service (NHS) Foundation Trust, Guy's Hospital, London, UK

    Fiona C Connell

  4. Bone Marrow Transplant Unit, Royal Hospital for Children, Bristol, UK

    Colin G Steward

  5. South West Thames Regional Genetics Service, St. George's University of London, London, UK

    Glen Brice, Shirley Hodgson & Sahar Mansour

  6. Haematology Unit, The Children's Hospital at Westmead, Sydney, Australia

    Tatjana Kilo

  7. Department of Clinical Genetics, St Michael's Hospital, Bristol, UK

    Sarah Smithson & Peter Lunt

  8. Department of Clinical Genetics, Yorkhill Hospital, Glasgow, UK

    Victoria A Murday

  9. Department of Paediatric Haematology, Alderhey Children's Hospital, Liverpool, UK

    Russell Keenan

  10. Institute of Medical Genetics, University Hospital of Wales, Cardiff, UK

    Daniela T Pilz

  11. Lymphatic Development Laboratory, Cancer Research UK London Research Institute, London, UK

    Ines Martinez-Corral & Taija Makinen

  12. Department of Cardiac and Vascular Sciences, St. George's University of London, London, UK

    Peter S Mortimer

Authors
  1. Pia Ostergaard
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  2. Michael A Simpson
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  4. Colin G Steward
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  8. Tatjana Kilo
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  9. Sarah Smithson
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  11. Victoria A Murday
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  12. Shirley Hodgson
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  15. Ines Martinez-Corral
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  16. Taija Makinen
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  17. Peter S Mortimer
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  18. Steve Jeffery
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  19. Richard C Trembath
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  20. Sahar Mansour
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Contributions

P.S.M., S.J., R.C.T. and S.M. jointly supervised the research. P.O., M.A.S., F.C.C., G.B., P.S.M., S.J., R.C.T. and S.M. conceived and designed the experiments. P.O., M.A.S., W.J.W., D.D., I.M.-C. and T.M. performed the experiments. P.O., M.A.S., D.D. and T.M. performed the statistical analysis. P.O., M.A.S. and T.M. analyzed the data. M.A.S., F.C.C., C.G.S., G.B., T.K., S.S., P.L., V.A.M., S.H., R.K., D.T.P., P.S.M., S.J., R.C.T. and S.M. contributed reagents, materials and analysis tools. M.A.S., S.J., R.C.T. and S.M. wrote the paper.

Corresponding author

Correspondence to Sahar Mansour.

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The authors declare no competing financial interests.

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Supplementary Methods, Supplementary Tables 1–3 and Supplementary Figures 1–3. (PDF 341 kb)

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Ostergaard, P., Simpson, M., Connell, F. et al. Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome). Nat Genet 43, 929–931 (2011). https://doi.org/10.1038/ng.923

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  • DOI: https://doi.org/10.1038/ng.923

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