Haematopoietic and immune defects associated with GATA2 mutation
Identifieur interne : 001D24 ( Main/Exploration ); précédent : 001D23; suivant : 001D25Haematopoietic and immune defects associated with GATA2 mutation
Auteurs : Matthew Collin ; Rachel Dickinson ; Venetia BigleySource :
- British Journal of Haematology [ 0007-1048 ] ; 2015.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : GATA2 Transcription Factor.
- genetics : Hematopoiesis, Immunity.
- Animals, Gene Expression Regulation, Genetic Association Studies, Genetic Predisposition to Disease, Haploinsufficiency, Heterozygote, Humans, Mutation.
Abstract
Heterozygous familial or sporadic
Url:
DOI: 10.1111/bjh.13317
PubMed: 25707267
PubMed Central: 4409096
Affiliations:
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Le document en format XML
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<series><title level="j">British Journal of Haematology</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>GATA2 Transcription Factor (genetics)</term>
<term>Gene Expression Regulation</term>
<term>Genetic Association Studies</term>
<term>Genetic Predisposition to Disease</term>
<term>Haploinsufficiency</term>
<term>Hematopoiesis (genetics)</term>
<term>Heterozygote</term>
<term>Humans</term>
<term>Immunity (genetics)</term>
<term>Mutation</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Facteur de transcription GATA-2 (génétique)</term>
<term>Haploinsuffisance</term>
<term>Humains</term>
<term>Hématopoïèse (génétique)</term>
<term>Hétérozygote</term>
<term>Immunité (génétique)</term>
<term>Mutation</term>
<term>Prédisposition génétique à une maladie</term>
<term>Régulation de l'expression des gènes</term>
<term>Études d'associations génétiques</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>GATA2 Transcription Factor</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Hematopoiesis</term>
<term>Immunity</term>
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<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteur de transcription GATA-2</term>
<term>Hématopoïèse</term>
<term>Immunité</term>
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<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Gene Expression Regulation</term>
<term>Genetic Association Studies</term>
<term>Genetic Predisposition to Disease</term>
<term>Haploinsufficiency</term>
<term>Heterozygote</term>
<term>Humans</term>
<term>Mutation</term>
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<term>Haploinsuffisance</term>
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<term>Hétérozygote</term>
<term>Mutation</term>
<term>Prédisposition génétique à une maladie</term>
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<front><div type="abstract" xml:lang="en"><p>Heterozygous familial or sporadic <italic>GATA2</italic>
mutations cause a multifaceted disorder, encompassing susceptibility to infection, pulmonary dysfunction, autoimmunity, lymphoedema and malignancy. Although often healthy in childhood, carriers of defective <italic>GATA2</italic>
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. <italic>GATA2</italic>
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.</p>
</div>
</front>
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<tree><noCountry><name sortKey="Bigley, Venetia" sort="Bigley, Venetia" uniqKey="Bigley V" first="Venetia" last="Bigley">Venetia Bigley</name>
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