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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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.
The authors declare no competing financial interests.
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