GATA2 deficiency

Abstract

Purpose of Review GATA2 deficiency is a germline disease which causes a wide spectrum of phenotypes including viral and bacterial infections, cytopenias, myelodysplasia, myeloid leukemias, pulmonary alveolar proteinosis and lymphedema. The age of clinical presentation ranges from early childhood to late adulthood, with most occurring in adolescence to early adulthood. We review the expanding GATA2 deficient phenotype, molecular genetics of disease, and developments in treatment. Recent Findings GATA2 mutations have been found in up to 10% of those with congenital neutropenia and/or aplastic anemia. Heterozygous mutations appear to cause haploinsufficiency due either to protein dysfunction or uniallelic reduced transcription. Disease-associated mutations in intronic regulatory elements or variations within the 5’ leader exons indicate that regulation of GATA2 is critical. Those with GATA2 mutations are at high risk for myelodysplasia (MDS), cytogenetic abnormalities, acute myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML). Bone marrow transplantation has been successful for both hematopoietic and pulmonary alveolar proteinosis repair. Summary GATA2 is a zinc finger transcription factor essential for embryonic and definitive hematopoiesis as well as lymphatic angiogenesis. GATA2 deficiency is caused by a variety of mutations in the GATA2 gene and can have variable presentation, onset and outcome. Patients are susceptible to mycobacterial, viral and fungal infections and can develop MDS, acute or chronic leukemias, lymphedema and pulmonary alveolar proteinosis. Hematopoietic stem cell transplantation (HSCT) reverses most of the clinical phenotype with good long-term outcomes.

Epidemiology of Norovirus Infection Among Immunocompromised Patients at a Tertiary Care Research Hospital, 2010–2013

“…The most common underlying diagnoses of those tested during the study period included those with hematologic malignancies (n = 122; 46%), PIDs (n = 53, 20%), and solid tumors (n = 44, 16%) (Table 1). In the group of 53 patients with PID disorders, the most common diagnoses were chronic granulomatous disease (n = 13; 25%) and GATA2 deficiency [33] (n = 10, 19%). …”

A genetic perspective on granulomatous diseases with an emphasis on mycobacterial infections

“…Distinct from the MSMD-causing genes mentioned above, a recently discovered monocytopenia and mycobacterial infection (MonoMAC) syndrome is caused by heterozygous loss of function mutations in GATA2 , a zinc finger transcription factor essential for embryonic and definitive hematopoiesis as well as lymphatic angiogenesis (15-17). …”

Tratamiento de la proteinosis alveolar primaria del adulto

“…En los casos de PAP congénita o hereditaria, el defecto en la eliminación del surfactante es debido a que se producen mutaciones en los genes que codifican la proteína del surfactante B (SP-B) 12 , la del surfactante C (SP-C) 13 , o en los genes que codifican las cadenas del receptor del GM-CSF (CSF2RA-␣ 14 y CSF2RB-␤ 15 ), impidiendo la unión del GM-CSF a su receptor de membrana 16 . También existen algunas mutaciones en genes de células germinales que van a producir varias enfermedades, entre ellas la PAP 17 . Finalmente, los casos de PAP secundaria se producen en varias enfermedades que provocan un descenso en el número o en la función del macrófago alveolar, como en el síndrome mielodisplásico, leucemias o linfomas 18 .…”