title: Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome.
abstract: The syndrome of monocytopenia, B-cell and NK-cell lymphopenia, and mycobacterial, fungal, and viral infections 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 frame shifts 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.
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892-1684, USA.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Hsu
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Sampaio
authors.forename: Javed
authors.initials: J
authors.lastname: Khan
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Calvo
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Lemieux
authors.forename: Smita Y
authors.initials: SY
authors.lastname: Patel
authors.forename: David M
authors.initials: DM
authors.lastname: Frucht
authors.forename: Donald C
authors.initials: DC
authors.lastname: Vinh
authors.forename: Roger D
authors.initials: RD
authors.lastname: Auth
authors.forename: Alexandra F
authors.initials: AF
authors.lastname: Freeman
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Olivier
authors.forename: Gulbu
authors.initials: G
authors.lastname: Uzel
authors.forename: Christa S
authors.initials: CS
authors.lastname: Zerbe
authors.forename: Christine
authors.initials: C
authors.lastname: Spalding
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Kuhns
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Paulson
authors.forename: Beatriz E
authors.initials: BE
authors.lastname: Marciano
authors.forename: Juan C
authors.initials: JC
authors.lastname: Gea-Banacloche
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Orange
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cuellar-Rodriguez
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Hickstein
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
mesh_terms: D050989:GATA2 Transcription Factor / Q000235:genetics*; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006801:Humans; D009000:Monocytes / Q000473:pathology*; D009154:Mutation / Q000235:genetics*; D009161:Mycobacterium / Q000472:pathogenicity*; D009164:Mycobacterium Infections / Q000209:etiology* / Q000473:pathology*; D013577:Syndrome
chemical_list: D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human