Presence of hypogammaglobulinemia and abnormal antibody responses inGATA2deficiency

The T354M mutation does not affect GATA2 expression or nuclear localization, but significantly impairs GATA2 binding to DNA and to the transcription factor PU.1, resulting in a dominant negative effect on transcriptional activation.9 The phenotypes associated with the T354M mutation include autosoma...

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Bibliographic Details
Published in:Journal of allergy and clinical immunology 2014-07, Vol.134 (1), p.223
Main Authors: Chou, Janet, Lutskiy, Maxim, Tsitsikov, Erdyni, Notarangelo, Luigi D, Geha, Raif S, Dioun, Anahita
Format: Article
Language:English
Subjects:
Age
Antigens
Ear diseases
Immune system
Immunoglobulins
Infections
Leukemia
Lymphocytes
Mutation
Plasma
Tetanus
Transcription factors
Vaccines
Viral infections
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Summary:The T354M mutation does not affect GATA2 expression or nuclear localization, but significantly impairs GATA2 binding to DNA and to the transcription factor PU.1, resulting in a dominant negative effect on transcriptional activation.9 The phenotypes associated with the T354M mutation include autosomal dominant MDS/acute myeloid leukemia, MDS with pancytopenia, multilineage cytopenias, and opportunistic infections.2,9-11 One patient with this mutation had 1 episode of parainfluenza and Mycoplasma infection with normal immunoglobulin levels,6 another had pneumonias limited to childhood,6 and 3 others had mycobacterial and viral infections.2,3,10 Four subjects were healthy into adulthood.9 Patient 1 presented with IgG2 and IgA deficiencies and an abnormal vaccine response, which has not been previously reported in patients with GATA2 mutations. Patient 2 had no history of recurrent infections despite her impaired lymphocyte proliferation to antigens. [...]in our patients, as in others,6 the same GATA2 mutation can result in different phenotypes.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2014.01.041