The spectrum of GATA2 deficiency syndrome

Abstract

Inherited or de novo germline heterozygous mutations in the gene encoding the transcription factor GATA2 lead to its deficiency; this results in a constellation of clinical features including infections with non-tuberculous mycobacterial, bacterial, fungal, and human papilloma virus infections, lymphedema, pulmonary alveolar proteinosis, and myelodysplasia. The onset, or even the presence, of disease is highly variable, even in kindreds with the identical mutation in GATA2. The clinical manifestations result from the loss of a multilineage progenitor which gives rise to B-lymphocytes, monocytes, Natural Killer (NK) cells and dendritic cells, leading to cytopenias of these lineages, and subsequent infections. The bone marrow failure is typically characterized by hypocellularity; dysplasia may be absent or subtle, but typically evolves into multilineage dysplasia with prominent dysmegakaryopoiesis, followed in some instances by progression to myeloid malignancies, specifically myelodysplastic syndrome (MDS), acute myelogenous leukemia (AML), and chronic myelomonocytic leukemia (CMML). The latter three malignancies often occur in the setting of monosomy 7, trisomy 8, and acquired mutations in ASXL1 or STAG2. Importantly, myeloid malignancy may represent the primary presentation of disease without recognition of other syndromic features. Allogeneic hematopoietic stem cell transplantation (HSCT) results in reversal of the phenotype. There remain important unanswered questions in GATA2 deficiency including: 1) why do some family members remain asymptomatic despite harboring deleterious mutations in GATA2, 2) what are the genetic changes that lead to myeloid progression, 3) what causes the apparent genetic anticipation, and 4) what is the role of preemptive HSCT.

A case of MYH7 and MYH9 genes variants with cardiomyopathy and macrothrombocytopenia

“…With the widespread availability of genetic testing for specific conditions, a broad spectrum of clinical features involving multiorgan systems that fall into overlapping phenotypes can be unified under a single monogenic disease, such as GATA2 deficiency, which encompasses MonoMAC syndrome, dendritic cell, monocyte B, and NK lymphoid (DCML) deficiency, Emberger syndrome, and familial predisposition to myelodysplastic syndrome and acute myeloid leukemia. 10 Pediatric patients, in particular, may present with various symptoms associated with a single disease. Consequently, pediatricians often attribute all symptoms to a single condition.…”

Effects of conceptus proteins on endometrium and blood leukocytes of dairy cattle using transcriptome and meta-analysis

“…Upstream analysis identified activation of transcription factors GATA binding protein 2 (GATA2), STAT6, and SMAD family member 3 (SMAD3). GATA2 is crucial for hematopoiesis and mutations in GATA2 gene leads to myelodysplasia and deficiency in B cells, monocytes, NK cells, and dendritic cells (Calvo & Hickstein, 2023; Nováková et al, 2016; Tsai et al, 1994). Moreover, STAT6 activation is mainly induced by IL4 that, in turn, supports B cell development, activation, and tolerance (Wang et al, 2021).…”

Inborn Errors of Immunity Causing Pediatric Susceptibility to Fungal Diseases

“…Pulmonary aspergillosis was reported in 5/274 (1.8%) of patients [ 60 , 110 ]. The GATA2 haploinsufficiency is a complex disorder predisposing to a variety of infections [ 111 , 112 , 113 , 114 , 115 , 116 , 117 ]. Pulmonary aspergillosis has been reported in 6/124 (4.8%) patients [ 118 ].…”