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Lymphedema Gene GATA2

In our continuing information regarding the genetics of lymphedema, yet another gene has been identified as causing primary lymphedema and with it acuta myeloid leukemia - Emberger Syndrome. This gene is called the GATA2.

Other conditions and syndromes associated with this gene include autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome and complex congenital immunodefficiency.

Treatment would be focused on (1) the leukemia,(2) lymphedema, and any additional specific complications that might arise.


Dec. 7, 2011

Abstracts and Studies

Loss-of-function germline GATA2 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature.

Dec 2011

Kazenwadel J, Secker GA, Liu YJ, Rosenfeld JA, Wildin RS, Cuellar-Rodriguez J, Hsu AP, Dyack S, Fernandez CV, Chong CE, Babic M, Bardy PG, Shimamura A, Zhang M, Walsh T, Holland SM, Hickstein DD, Horwitz MS, Hahn CN, Scott HS, Harvey NL. Source Division of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia; Abstract Recent work has established that heterozygous germline GATA2 mutations predispose carriers to familial myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML), “MonoMAC” syndrome and DCML deficiency. Here, we describe a previously unreported MDS family carrying a missense mutation in GATA2 (p.Thr354Met), one patient with MDS/AML carrying a frameshift mutation in GATA2 (p.Leu332Thrfs*53), another individual with MDS harboring a GATA2 splice site mutation, and three patients exhibiting MDS or MDS/AML who have large deletions encompassing the GATA2 locus. Intriguingly, two patients with GATA2 deletions and one with a frameshift mutation who have MDS/AML or “MonoMAC” syndrome also have primary lymphedema. Primary lymphedema occurs as a result of aberrations in the development and/or function of lymphatic vessels, spurring us to investigate whether GATA2 plays a role in the lymphatic vasculature. We demonstrate here that GATA2 protein is present at high levels in the leaflets of lymphatic vessel valves, and that GATA2 controls the expression of genes that play key roles in programming lymphatic valve development. Our data expand the phenotypes associated with germline GATA2 mutations to include predisposition to primary lymphedema and suggest that complete haploinsufficiency or loss-of-function (LOF) of GATA2, rather than missense mutations, is the key predisposing factor for lymphedema onset. Moreover, we reveal a crucial role for GATA2 in lymphatic vascular development, particularly in controlling valve development and/or function.

Full text article: Blood Journal

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

Sept 2011

Ostergaard P, Simpson MA, Connell FC, Steward CG, Brice G, Woollard WJ, Dafou D, Kilo T, Smithson S, Lunt P, Murday VA, Hodgson S, Keenan R, Pilz DT, Martinez-Corral I, Makinen T, Mortimer PS, Jeffery S, Trembath RC, Mansour S.


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


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.

Nature Genetics

Altered hematopoietic cell gene expression precedes development of therapy-related myelodysplasia/acute myeloid leukemia and identifies patients at risk.

Nov 2011

Li L, Li M, Sun C, Francisco L, Chakraborty S, Sabado M, McDonald T, Gyorffy J, Chang K, Wang S, Fan W, Li J, Zhao LP, Radich J, Forman S, Bhatia S, Bhatia R. Source City of Hope National Medical Center, Duarte, CA 91010, USA.


Therapy-related myelodysplasia or acute myeloid leukemia (t-MDS/AML) is a major complication of cancer treatment. We compared gene expression in CD34+ cells from patients who developed t-MDS/AML after autologous hematopoietic cell transplantation (aHCT) for lymphoma with controls who did not develop t-MDS/AML. We observed altered gene expression related to mitochondrial function, metabolism, and hematopoietic regulation in pre-aHCT samples from patients who subsequently developed t-MDS/AML. Progression to overt t-MDS/AML was associated with additional alterations in cell-cycle regulatory genes. An optimal 38-gene PBSC classifier accurately distinguished patients who did or did not develop t-MDS/AML in an independent group of patients. We conclude that genetic programs associated with t-MDS/AML are perturbed long before disease onset, and accurately identify patients at risk for this complication.

Cancer Cell

GATA2 GATA binding protein 2 [ Homo sapiens ]

Official Symbol

GATA2provided by HGNC

Official Full Name

GATA binding protein 2provided by HGNC

Primary source


See related

Ensembl: ENSG00000179348; HPRD:00673; MIM:137295; Vega:OTTHUMG00000159689

Gene type: protein coding

RefSeq status: Reviewed

Organism Homo sapiens


Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo

Also known as DCML; NFE1B; MONOMAC

Summary This gene encodes a member of the GATA family of zinc-finger transcription factors that are named for the consensus nucleotide sequence they bind in the promoter regions of target genes. The encoded protein plays an essential role in regulating transcription of genes involved in the development and proliferation of hematopoietic and endocrine cell lineages. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

Genomic Context

Location : 3q21.3 Sequence : Chromosome: 3; NC_000003.11 (128198265..128212030, complement)

See GATA2 in Epigenomics, MapViewer


External Links

Altered hematopoietic cell gene expression precedes development of therapy-related myelodysplasia/acute myeloid leukemia and identifies patients at risk. Nov 2011

Cell Press

Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome) Aug 2011

Nature Genetics

Endothelial transcription factor GATA-2


Myelodysplastic Syndromes

Leukemia & Lymphoma Society

The role of hematopoietic cell transplantation as therapy for myelodysplasia.

Clinical Haematology

GATA2 Is Associated with Familial Early-Onset Coronary Artery Disease

GATA2 antibody ( 10R-1758 )

Gata2 - Catalogue of Somatic Mutations in Cancer

Mutations in GATA2 identified as cause of Emberger syndrome

Loss-of-function germline GATA2 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature

Lymphedema People Related Internal Links

Lymphedema People Resources

Lymphedema Family Study

Please support this important work

Welcome to the Lymphedema Family Study at the University of Pittsburgh! The goal of this project is to identify genes responsible for primary lymphedema. It is our hope that a new understanding of the genetic basis of inherited lymphedema will provide insight into its treatment and contribute to early identification of individuals at risk. Click on the links to the left for frequently asked questions about this condition, information about the inheritance of primary lymphedema, previous investigations into the genetic aspects of lymphedema, an update of our research, and listings of our references and other lymphedema websites.

This study does not involve diagnosis or treatment of lymphedema, and it was not designed to provide any direct benefit to the participants. However, it is our hope that it will benefit many lymphedema patients in the future. If there are at least two people (including you) in your family with primary lymphedema, and you would like more information on how to become involved in the Lymphedema Family Study, please contact the coordinator of this study, Kelly Knickelbein, M.S., at the address or phone number below: Lymphedema Family Study University of Pittsburgh Department of Human Genetics A300 Crabtree Hall, GSPH Pittsburgh, PA 15261 Phone: (412) 624-4657 or (800) 263-2152 e-mail:

Please be sure to include the words LYMPHEDEMA or GENETIC in your subject line.

Family Study Program

The Lymphatic Research Foundation

The Lymphatic Research Foundation is a 501©(3) not-for profit organization whose mission is to advance research of the lymphatic system and to find the cause of and cure for lymphatic diseases, lymphedema, and related disorders.


lymphedema_gene_gata2.txt · Last modified: 2012/10/16 14:40 (external edit)