Congenital transfusion-dependent anemia and thrombocytopenia with myelodysplasia due to a recurrent GATA1(G208R) germline mutation.

Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K (Impact Factor: 10.16). 03/2008; 22(2):432-4. DOI: 10.1038/sj.leu.2404904
Source: PubMed
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    Platelets 08/2013; · 2.63 Impact Factor
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    ABSTRACT: Most heritable anemias are caused by mutations in genes encoding globins, red blood cell (RBC) membrane proteins or enzymes in the glycolytic and hexose monophosphate shunt pathways. A less common class of genetic anemia is caused by mutations that alter the functions of erythroid transcription factors (TFs). Many TF mutations associated with heritable anemia cause truncations or amino acid substitutions, resulting in the production of functionally altered proteins. Characterization of these mutant proteins has provided insights into mechanisms of gene expression, hematopoietic development and human disease. Mutations within promoter or enhancer regions that disrupt TF binding to essential erythroid genes also cause anemia and heritable variations in RBC traits, such as fetal hemoglobin content. Defining the latter may have important clinical implications for de-repressing fetal hemoglobin synthesis to treat sickle cell anemia and β thalassemia. Functionally important alterations in genes encoding TFs or their cognate cis elements are likely to occur more frequently than currently appreciated, a hypothesis that will soon be tested through ongoing genome wide association studies and the rapidly expanding use of global genome sequencing for human diagnostics. Findings obtained through such studies of RBCs and associated diseases are likely generalizable to many human diseases and quantitative traits.
    Blood 03/2014; · 9.78 Impact Factor
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    ABSTRACT: GATA-1, an X-linked gene, encodes a transcription factor that plays a role in erythropoiesis and megakaryopoiesis. GATA-1 mutations have been associated with various diseases, such as X-linked thrombocytopenia. ALAS2 is an X-linked erythroid-specific isoenzyme expressed during erythropoiesis. Mutations of ALAS2 were associated with X-linked sideroblastic anemia. We report a case of newborn twin boy with anemia and thrombocytopenia at birth. A bone marrow biopsy at 4 months of age showed marked dyserythropoiesis, dysmegakaryopoiesis, and rare ringed sideroblasts. Gene sequencing study showed a previously reported mutation in GATA-1 at c.622G>A location (G208R) and a novel ALAS2 mutation at c.1436G>A location (R479Q).
    American journal of blood research. 01/2014; 4(1):41-5.


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