title: Haematopoietic and immune defects associated with GATA2 mutation.
abstract: Heterozygous familial or sporadic GATA2 mutations cause a multifaceted disorder, encompassing susceptibility to infection, pulmonary dysfunction, autoimmunity, lymphoedema and malignancy. Although often healthy in childhood, carriers of defective GATA2 alleles develop progressive loss of mononuclear cells (dendritic cells, monocytes, B and Natural Killer lymphocytes), elevated FLT3 ligand, and a 90% risk of clinical complications, including progression to myelodysplastic syndrome (MDS) by 60 years of age. Premature death may occur from childhood due to infection, pulmonary dysfunction, solid malignancy and MDS/acute myeloid leukaemia. GATA2 mutations include frameshifts, amino acid substitutions, insertions and deletions scattered throughout the gene but concentrated in the region encoding the two zinc finger domains. Mutations appear to cause haplo-insufficiency, which is known to impair haematopoietic stem cell survival in animal models. Management includes genetic counselling, prevention of infection, cancer surveillance, haematopoietic monitoring and, ultimately, stem cell transplantation upon the development of MDS or another life-threatening complication.
authors.affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Collin
authors.forename: Rachel
authors.initials: R
authors.lastname: Dickinson
authors.forename: Venetia
authors.initials: V
authors.lastname: Bigley
mesh_terms: D000818:Animals; D050989:GATA2 Transcription Factor / Q000235:genetics*; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D057895:Haploinsufficiency; D006410:Hematopoiesis / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007109:Immunity / Q000235:genetics*; D009154:Mutation
chemical_list: D050989:GATA2 Transcription Factor
keywords: GATA2; bone marrow failure; immunodeficiency