The Protean Manifestations of GATA2 Deficiency Across the Lifespan

The Protean Manifestations of GATA2 Deficiency Across the Lifespan

Air date: Wednesday, December 11, 2013, 3:00:00 PM

Runtime: 01:07:23

Description: The NIH Director's Wednesday Afternoon Lecture Series

The Annual G. Burroughs Mider Lecture

GATA binding factor 2 (GATA2) was initially cloned (1991) as a critical regulator of murine endothelial development, the complete absence of which was incompatible with life. Subsequent work confirmed that it was also critical for hematopoiesis, erythropoiesis, and macrophage function. After almost 20 years of characterization of patients with disseminated mycobacterial infections who had monocytopenia, B cell and NK (natural killer) cell cytopenia, Steve Holland's group found heterozygous mutations in the same transcription factor, GATA2, accounting for their disease. However, in humans these heterozygous mutations cause haploinsufficiency and underlie myelodysplasia, myeloid leukemia, pulmonary alveolar proteinosis, classical NK cell deficiency, and lymphedema. GATA2 deficiency causes a late onset congenital immunodeficiency that can be cured by bone marrow transplantation. GATA2 is involved in many processes with virtually complete penetrance but highly variable expression, suggesting that genetic and epigenetic modifiers are important.

Author: Dr. Steven Holland, NIAID Laboratory of Clinical Infectious Diseases, NIH