Deficit of GATA-2 transcription factor: new immunodeficiency syndrome with broad phenotype. First patients diagnosed in the Czech Republic and review of the literature
Authors:
A. Janda 1; E. Mejstříková 2; U. Salzer 1; J. Grimová 3; T. Svobodová 4; M. Suková 2; M. Nováková 2; P. Hubáček 2,9; Z. Zemanová 5; J. Čermák 6; Z. Černá 7; A. Vítek 6; A. Šedivá 8; O. Hrušák 2; J. Starý 2
Authors‘ workplace:
Centre of Chronic Immunodeficiency (CCI), University Medical Centre and University of Freiburg, Freiburg im Breisgau, Německo
1; Klinika dětské hematologie a onkologie UK 2. LF a FN Motol, Prahapřednosta prof. MUDr. J. Starý, DrSc.
2; Onkologická klinika UK 1. LF a Fakultní Thomayerovy nemocnice, Prahapřednosta MUDr. T. Buchler, Ph. D.
3; Pediatrická klinika UK 2. LF a FN Motol, Prahapřednosta prof. MUDr. J. Lebl, CSc.
4; Ústav lékařské biochemie a laboratorní diagnostiky UK 1. LF a VFN, Prahapřednosta prof. MUDr. T. Zima, DrSc., MBA
5; Ústav hematologie a krevní transfuze, Prahaředitel prof. MUDr. M. Trněný, CSc.
6; Dětská klinika Lékařské fakulty Univerzity Karlovy, Plzeňpřednosta doc. MUDr. J. Kobr, Ph. D.
7; Ústav imunologie UK 2. LF a FN Motol, Prahapřednostka prof. MUDr. J. Bartůňková, DrSc., MBA
8; Ústav lékařské mikrobiologie UK 2. LF a FN Motol, Prahapřednosta doc. MUDr. P. Dřevínek, Ph. D.
9
Published in:
Čes-slov Pediat 2013; 68 (2): 101-112.
Category:
Case Report
Overview
Defects in the zinc-finger transcription factor GATA-2 gene have been recently identified in variable phenotypes associated with myeloid malignancies - myelodysplastic syndrome and acute myeloid leukaemia (MDS/AML): DCML (dendritic cell, monocyte, B-lymphocyte and NK-lymphocyte) deficiency or MonoMAC syndrome (monocytopenia with Mycobaterium avium complex infections), Emberger syndrome (early onset primary lymphoedema, multiple warts, sensorineural deafness, dysmorphism); and familial MDS/AML with no additional known phenotype.
In the Czech Republic there have been 2 patients diagnosed with GATA-2 deficiency so far. The first patient was investigated at the age of 12 years for recurrent urinary tract infections, aphtous stomatitis, herpetic skin infections and bronchial asthma; leukopenia, mild macrocytic anaemia and markedly low number of B lymphocytes with normal immunoglobulin levels were found. In the following 10 years bicytopenia progressed into a hypoplastic MDS. The girl underwent successful transplantation of haematopoietic stem cells from her HLA-identical healthy sister. Retrospectively, a heterozygous mutation (c.1187 G>A, p.R396Q) in GATA-2 has been identified. The second patient is 17 year-old boy investigated for an advanced interstitial pulmonary process with cystic remodelling of pulmonary parenchyma accompanied by signs of vasculitis. Suspicion of GATA-2 genetic defect was based on profound monocytopenia and B-cell lymphopenia. By molecular genetic analysis of GATA-2 heterozygous mutation (c.1081 C>T, p.R361C) was revealed.
Our experience corresponds with the published data on the broad phenotypic variability in patients with GATA-2 mutations. Establishment of the diagnosis of GATA-2 deficiency should lead to closer follow-up of the affected individuals and earlier allogeneic haematopoietic stem cell transplantation in case of clonal progression (MDS/AML).
Key words:
primary immunodeficiency, GATA-2 deficiency, MonoMAC, dendritic cell, monocyte, B lymphocyte, and natural killer lymphocyte deficiency (DCML), Emberger syndrome; pulmonary alveolar proteinosis, haematopoietic stem cell transplantation
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Neonatology Paediatrics General practitioner for children and adolescentsArticle was published in
Czech-Slovak Pediatrics
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