An autosomal dominant disorder (OMIM:614172) characterised by cytogenetic defects, monocytopaenia, and B and NK cell lymphopaenia. The genetic and haematologic defects lead to increased susceptibility to disseminated nontuberculous mycobacterial, viral–especially HPV, and fungal infections, primarily histoplasmosis, and molds, pulmonary alveolar proteinosis, and increased susceptibility to malignancy, including myelodysplasia, myeloid leukemia, vulvar and cervical cancer, Bowen’s disease of the vulva, leiomyosarcoma, and metastatic melanoma. MonoMAC syndrome is also associated with automimmune disease, including lupus like changes, primary biliary cirrhosis and aggressive multiple sclerosis.
Molecular pathology Defects* of GATA2, which encodes a protein that plays an essential role in regulating transcription of genes involved in the development and proliferation of haematopoietic and endocrine cell lineages, cause monoMAC syndrome.
*Missense mutations affecting the zinc finger-2 domain and insertion/deletion mutations leading to frameshifts and premature termination.
Note: The OMIM preferred term for monoMAC syndrome is immunodeficiency 21.
References Blood 115 (8): 1519–29. doi:10.1182/blood-2009-03-208629