Blood Journal
Leading the way in experimental and clinical research in hematology

Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome

  1. Amy P. Hsu1,
  2. Elizabeth P. Sampaio1,
  3. Javed Khan2,
  4. Katherine R. Calvo3,
  5. Jacob E. Lemieux4,
  6. Smita Y. Patel5,
  7. David M. Frucht6,
  8. Donald C. Vinh1,
  9. Roger D. Auth6,
  10. Alexandra F. Freeman1,
  11. Kenneth N. Olivier1,
  12. Gulbu Uzel1,
  13. Christa S. Zerbe1,
  14. Christine Spalding1,
  15. Stefania Pittaluga7,
  16. Mark Raffeld7,
  17. Douglas B. Kuhns8,
  18. Li Ding1,
  19. Michelle L. Paulson8,
  20. Beatriz E. Marciano1,
  21. Juan C. Gea-Banacloche9,
  22. Jordan S. Orange10,
  23. Jennifer Cuellar-Rodriguez1,
  24. Dennis D. Hickstein9, and
  25. Steven M. Holland1,*
  1. 1 Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, MD, United States;
  2. 2 Oncogenomics Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD, United States;
  3. 3 Hematology Section, Department of Laboratory Medicine, Warren Grant Magnuson Clinical Center, Bethesda, MD, United States;
  4. 4 Laboratory of Malaria and Vector Research, NIAID, NIH, Bethesda, MD, United States;
  5. 5 John Radcliffe Hospital, Oxford University, London, United Kingdom;
  6. 6 Center for Drug Evaluation and Research, FDA, Bethesda, MD, United States;
  7. 7 Laboratory of Pathology, National Cancer Institute, Bethesda, MD, United States;
  8. 8 SAIC-Frederick Inc., NCI-Frederick, Frederick, MD, United States;
  9. 9 Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD, United States;
  10. 10 Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, United States
  1. * Corresponding author; email: smh{at}


The syndrome of monocytopenia, B and NK cell lymphopenia and mycobacterial, fungal and viral infections (MonoMAC) is associated with myelodysplasia, cytogenetic abnormalities, pulmonary alveolar proteinosis and myeloid leukemias. Both autosomal dominant and sporadic cases occur. We identified 12 distinct mutations in GATA2 affecting 20 patients and relatives with this syndrome, including recurrent missense mutations affecting the zinc finger-2 domain (R398W and T354M), suggesting dominant interference of gene function. Four discrete insertion/deletion mutations leading to frameshifts and premature termination implicate haploinsufficiency as a possible mechanism of action as well. These mutations were found in hematopoietic and somatic tissues, and several were identified in families, indicating germline transmission. Thus, GATA2 joins RUNX1 and CEBPA not only as a familial leukemia gene, but also as a cause of a complex congenital immunodeficiency that evolves over decades and combines predisposition to infection and myeloid malignancy.

  • Submitted May 24, 2011.
  • Accepted May 31, 2011.