| dbo:abstract
|
- GATA2 deficiency is a grouping of several disorders caused by common defect, viz., familial or sporadic inactivating mutations in one of the two parental GATA2 genes. Being the gene haploinsufficient, mutations that cause a reduction in the cellular levels of the gene's product, GATA2, are autosomal dominant. The GATA2 protein is a transcription factor critical for the embryonic development, maintenance, and functionality of blood-forming, lymphatic-forming, and other tissue-forming stem cells. In consequence of these mutations, cellular levels of GATA2 are deficient and individuals develop over time hematological, immunological, lymphatic, or other presentations that may begin as apparently benign abnormalities but commonly progress to severe organ (e.g. lung) failure, opportunistic infections, virus infection-induced cancers, the myelodysplastic syndrome, and/or leukemia. GATA2 deficiency is a life-threatening and precancerous condition. The various presentations of GATA2 deficiency include: 1) Monocytopenia and Mycobacterium Avium Complex/Dendritic Cell, Monocyte, B and NK Lymphocyte deficiency (i.e. MonoMAC or MonoMAC/DCML); 2) Emberger syndrome; 3) familial myelodysplastic syndrome/acute myeloid leukemia (i.e. familial MDS/AML); 3) chronic myelomonocytic leukemia (i.e. CMML); and 4) other anomalies such as aplastic anemia, chronic neutropenia, and wide-ranging immunological defects. Each of these presentations is characterized by a specific constellation of signs and symptoms but often includes signs and symptoms more characteristic of other GATA2 deficiency presentations. Furthermore, individuals with identical GATA2 gene mutations can exhibit very different presentations. Prior to 2011, MonoMAC and the Emberger syndrome were clinically defined as unrelated genetic disorders. In 2011, however, all cases of both disorders were found to be caused by inactivating mutations in the GATA2 gene. Subsequently, some but not all cases of an expanding list of other well-defined disorders have been attributed to inactivating GATA2 mutations. While MonoMAC, the Emberger syndrome, and the growing list of all other disorders marked by inactivating GATA2 gene mutations are now being classified as a single clinical entity termed GATA2 deficiency, MonoMAC and the Emberger syndrome are sometimes still regarded as separate clinical entities. Here, GATA2 deficiency is taken to include all disorders caused by inactivating GATA2 mutations. Defined as such, GATA2 deficiency is an unexpectedly common underlying cause for a growing list of disorders. Importantly, however, its treatment differs critically from that used to treat cases of these disorders which are not due to GATA2 deficiency. (en)
|
| rdfs:comment
|
- GATA2 deficiency is a grouping of several disorders caused by common defect, viz., familial or sporadic inactivating mutations in one of the two parental GATA2 genes. Being the gene haploinsufficient, mutations that cause a reduction in the cellular levels of the gene's product, GATA2, are autosomal dominant. The GATA2 protein is a transcription factor critical for the embryonic development, maintenance, and functionality of blood-forming, lymphatic-forming, and other tissue-forming stem cells. In consequence of these mutations, cellular levels of GATA2 are deficient and individuals develop over time hematological, immunological, lymphatic, or other presentations that may begin as apparently benign abnormalities but commonly progress to severe organ (e.g. lung) failure, opportunistic infec (en)
|
