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. 2011 Sep 8;118(10):2653-5.
doi: 10.1182/blood-2011-05-356352. Epub 2011 Jun 13.

Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome

Amy P Hsu  1 , Elizabeth P Sampaio, Javed Khan, Katherine R Calvo, Jacob E Lemieux, Smita Y Patel, David M Frucht, Donald C Vinh, Roger D Auth, Alexandra F Freeman, Kenneth N Olivier, Gulbu Uzel, Christa S Zerbe, Christine Spalding, Stefania Pittaluga, Mark Raffeld, Douglas B Kuhns, Li Ding, Michelle L Paulson, Beatriz E Marciano, Juan C Gea-Banacloche, Jordan S Orange, Jennifer Cuellar-Rodriguez, Dennis D Hickstein, Steven M Holland
Affiliations

Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome

Amy P Hsu et al. Blood. .

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.

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Figures

Figure 1
Figure 1
GATA2 gene. (A) Genomic organization of GATA2 showing 2 5′-untranslated and 5 coding exons. Wider boxes represent coding regions. Insertion/deletion mutations predicted to result in null alleles are shown above. (B) Protein domains of GATA2, showing N- and C-terminal zinc fingers (ZF-1, ZF-2) and nuclear localization signal (N). (C) Missense and in-frame deletion mutations identified within ZF-2. Superscript numerals indicate the number of independent mutations.
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Comment in

  • GATA2 finds its macrophage niche.
    Migliaccio AR, Bieker JJ. Migliaccio AR, et al. Blood. 2011 Sep 8;118(10):2647-9. doi: 10.1182/blood-2011-06-362772. Blood. 2011. PMID: 21903902 No abstract available.

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References

    1. Vinh DC, Patel SY, Uzel G, et al. Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia. Blood. 2010;115(8):1519–1529. - PMC - PubMed
    1. Bigley V, Haniffa M, Doulatov S, et al. The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency. J Exp Med. 2011;208(2):227–234. - PMC - PubMed
    1. Calvo KR, Vinh DC, Maric I, et al. Myelodysplasia in autosomal dominant and sporadic monocytopenia immunodeficiency syndrome: diagnostic features and clinical implications. Haematologica. 2011 Apr 20; Epub ahead of print. - PMC - PubMed
    1. Scott HS, Hahn CN, Carmichael CL, et al. GATA2 is a new predisposition gene for familial myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). ASH Annual Meeting Abstracts. 2010;116(21):LBA-3.
    1. Adzhubei IA, Schmidt S, Peshkin L, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7(4):248–249. - PMC - PubMed

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