Deficit of GATA-2 transcription factor: new immunodeficiency syndrome with broad phenotype. First pa- tients diagnosed in the Czech Republic and review of the literature.

Abstract

Defects in the zinc-finger transcription factor GATA-2 gene have been recently identified in variable phenotypes as- sociated 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 investi- gated 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 success- ful 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 muta- tions. 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).