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Haematopoietic and immune defects associated with GATA2 mutation
Author(s) -
Collin Matthew,
Dickinson Rachel,
Bigley Venetia
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13317
Subject(s) - gata2 , immunology , haematopoiesis , immune dysregulation , myeloid , malignancy , stem cell , mutation , bone marrow failure , cancer research , medicine , biology , immune system , genetics , gene
Summary Heterozygous familial or sporadic GATA 2 mutations cause a multifaceted disorder, encompassing susceptibility to infection, pulmonary dysfunction, autoimmunity, lymphoedema and malignancy. Although often healthy in childhood, carriers of defective GATA 2 alleles develop progressive loss of mononuclear cells (dendritic cells, monocytes, B and Natural Killer lymphocytes), elevated FLT 3 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. GATA 2 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.