Abstract
The GATA2 gene codes for a hematopoietic transcription factor that through its two zinc fingers (ZF) can occupy GATA-DNA motifs in a countless number of genes. It is crucial for the proliferation and maintenance of hematopoietic stem cells. During the past 5 years, germline heterozygous mutations in GATA2 were reported in several hundred patients with various phenotypes ranging from mild cytopenia to severe immunodeficiency involving B cells, natural killer cells, CD4(+) cells, monocytes and dendritic cells (MonoMAC/DCML), and myeloid neoplasia. Some patients additionally show syndromic features such as congenital deafness and lymphedema (originally defining the Emberger syndrome) or pulmonary disease and vascular problems. The common clinical denominator in all reported cohorts is the propensity for myeloid neoplasia (myelodysplastic syndrome [MDS], myeloproliferative neoplasms [MPN], chronic myelomonocytic leukemia [CMML], acute myeloid leukemia [AML]) with an overall prevalence of approximately 75% and a median age of onset of roughly 20 years. Three major mutational types are encountered in GATA2-deficient patients: truncating mutations prior to ZF2, missense mutations within ZF2, and noncoding variants in the +9.5kb regulatory region of GATA2. Recurrent somatic lesions comprise monosomy 7 and trisomy 8 karyotypes and mutations in SETBP1 and ASXL1 genes. The high risk for progression to advanced myeloid neoplasia and life-threatening infectious complications guide decision-making towards timely stem cell transplantation.