| dbo:abstract
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- The Emberger syndrome is a rare, autosomal dominant, genetic disorder caused by familial or sporadic inactivating mutations in one of the two parental GATA2 genes. The mutation results in a haploinsufficiency (i.e. reduction) in the levels of the gene's product, the GATA2 transcription factor. This transcription factor is critical for the embryonic development, maintenance, and functionality of blood-forming, lympathic-forming, and other tissues. The syndrome includes as its primary symptoms: serious abnormalities of the blood such as the myelodysplastic syndrome and acute myeloid leukemia; lymphedema (i.e. fluid retention and tissue swelling caused by a compromised lymphatic system) of the lower limbs, and sensorineural hearing loss. However, the anomalies caused by GATA2 mutations are highly variable with some individuals showing little or no such symptoms even in old age while others exhibit non-malignant types of hematological anomalies; lymphedema in areas besides the lower limbs, little or no hearing loss; or anomalies in other tissues. The syndrome may present with relatively benign signs and/or symptoms and then progress rapidly or slowly (i.e. over years or decades) to the myelodysplastic syndrome and/or acute myeloid leukemia. Alternatively, it may present with one of the latter two life-threatening disorders. The Emberger syndrome is only one of the manifestations of inactivating GATA2 mutations. Other manifestations include: 1 Monocytopenia and Mycobacterium Avium Complex/Dendritic Cell, Monocyte, B and NK Lymphocyte deficiency (i.e. MonoMAC or MonoMAC/DCML); 2) familial myelodysplastic syndrome/acute myeloid leukemia (i.e. familial MDS/AML); 3) chronic myelomonocytic leukemia; 4) pediatric myelodysplastic syndrome; and 5) various other hematological abnormalities such as aplastic anemia, anemia, chronic neutropenia; and/or various immunological defects. Individuals with the Emberger syndrome may exhibit signs or symptoms that are more characteristic of the latter manifestations. Since most individuals with inactivating GATA2 mutations progress to a leukemic disorder, the Emberger syndrome is a Precancerous condition. The age of onset and types of symptoms that occur in individuals afflicted with the Emberger syndrome are highly variable even in family members presumed to have identical GATA2 gene mutations. This variability as well as the variability in the different manifestations of GATA2-inactivating mutations are not fully understood. They likely relate, at least in part, to: individual differences in the: 1) levels of the GATA2 transcription factor which are expressed; 2) genetic backgrounds; 3) occurrence of illnesses or other events that stress the bone marrow; and, possibly, 4) development of other "secondary" genetic abnormalities that often develop during the course of these disorders. Because of these many complexities, recent reports have grouped together all of the different manifestations of GATA2 inactivating mutations into a single pleotropic genetic disorder termed GATA2 deficiency, GATA2 haploinsufficiency, or the GATA2 deficiency syndrome. Even currently, however, the Emberger syndrome (e.g. its MIM entry is #614038) and MonoMac/DCML (e.g. its MIM entry is #614172) are often classified as distinct clinical disorders. The Emberger syndrome is here considered as a distinct disorder. (en)
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| rdfs:comment
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- The Emberger syndrome is a rare, autosomal dominant, genetic disorder caused by familial or sporadic inactivating mutations in one of the two parental GATA2 genes. The mutation results in a haploinsufficiency (i.e. reduction) in the levels of the gene's product, the GATA2 transcription factor. This transcription factor is critical for the embryonic development, maintenance, and functionality of blood-forming, lympathic-forming, and other tissues. The syndrome includes as its primary symptoms: serious abnormalities of the blood such as the myelodysplastic syndrome and acute myeloid leukemia; lymphedema (i.e. fluid retention and tissue swelling caused by a compromised lymphatic system) of the lower limbs, and sensorineural hearing loss. However, the anomalies caused by GATA2 mutations are hi (en)
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