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

Article metrics


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Clinical and genetic findings in Emberger syndrome.

Accession codes


NCBI Reference Sequence


  1. 1

    Mansour, S. et al. Am. J. Med. Genet. 152A, 2287–2296 (2010).

  2. 2

    Song, W.-J. et al. Nat. Genet. 23, 166–175 (1999).

  3. 3

    Smith, M.L. et al. N. Engl. J. Med. 351, 2403–2407 (2004).

  4. 4

    Preudhomme, C. et al. Blood 96, 2862–2869 (2000).

  5. 5

    Pabst, T. et al. Nat. Genet. 27, 263–270 (2001).

  6. 6

    Tsai, F.-Y. et al. Nature 371, 221–226 (1994).

  7. 7

    Rodrigues, N.P. et al. Blood 112, 4862–4873 (2008).

  8. 8

    Zheng, R. & Blobel, G.A. Genes Cancer 1, 1178–1188 (2010).

  9. 9

    Zhang, S.-J. et al. Proc. Natl. Acad. Sci. USA 105, 2076–2081 (2008).

  10. 10

    Callier, P. et al. Am. J. Med. Genet. 149A, 1323–1326 (2009).

  11. 11

    Tong, Q. et al. Mol. Cell. Biol. 25, 706–715 (2005).

  12. 12

    Khandekar, M. et al. Development 134, 1703–1712 (2007).

  13. 13

    Haugas, M. et al. Dev. Dyn. 239, 2452–2469 (2010).

  14. 14

    Hsu, A.P. et al. Blood published online, doi:10.1182/blood-2011-05-356352 (13 June 2011).

  15. 15

    Dickinson, R.E. et al. Blood published online, doi:10.1182/blood-2011-06-360313 (15 July 2011).

Download references


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.

Author information

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.

Correspondence to Sahar Mansour.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

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

Rights and permissions

Reprints and Permissions

About this article

Further reading