Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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Congenital dyserythropoietic anemia type I (CDA-I) is a rare genetic disease that affects erythropoiesis. On the other hand, hemoglobin H (HbH) disease is a severe form of alpha-thalassemia. We herein present ultrastructural and immunocytochemical data concerning the first reported case of congenital anemia with clinical and molecular diagnosis of HbH disease complicated by CDA-I-specific dysplasies of the erythroid cells. Fine structure and transmission electron microscope immunolabeling analysis of the bone marrow and peripheral blood samples were consistent with a potential co-existence of the two defects in the same patient, producing a novel and diagnostically important dyserythropoietic profile. In the patient under investigation both nuclear and plasma membrane of the erythroid cells are almost equally defective. The unknown defect causes the concomitant precipitation of beta- and alpha-globin chains (or hemoglobin), along with an unidentified protein(s). The unusual inclusions gain access to the euchromatin area and exhibit higher affinity for the plasma membrane than the classic inclusions of precipitated alpha- or beta-globin chains seen in thalassemia. The affected erythroid precursors are presented with severe nuclear distortions, endonuclear globin loads, morphological evidence of apoptosis and increased erythrophagocytosis. Plasma membrane distortions and the rate of protein precipitation were aggravated with differentiation. Our findings provide additional evidence for a specific activation of a beta-thalassemic-like mechanism in CDA-I, containing not only the hemoglobin biosynthesis as previously suggested, and interpret the prototypal hematological portrait, which is an HbH disease, modified and partially counterbalanced by the effect of CDA-I or an unidentified CDA-I-like disease. The reported data describe the complexity of the interactions between the CDA-I and the HbH disease, revealing essential pathogenic events of the novel anemia and, indirectly, of the CDA-I.
Blood Cells Mol Dis
PMID:Ultrastructural characterization of the erythroid cells in a novel case of congenital anemia. 1266 85

Congenital dyserythropoietic anemias (CDA) are genetic disorders characterized by anemia and ineffective erythropoiesis. Three main types of CDA have been distinguished: CDA I, CDAII and CDA III, whose loci have been already mapped. After the identification of the locus for CDA II, also known as HEMPAS (hereditary erythroblast multinuclearity with positive acidified serum test), on the long arm of chromosome 20 (20q11.2) we have analyzed by a mutational search seven candidate genes in a large series of CDA II patients. In particular, the following genes have been investigated: integrin beta 4 binding protein, ribophorin II, ubiquitin protein ligase ITCH, mannosil-oligosaccharide alpha-1,2-mannosidase like protein, erythrocyte protein band 4.1 like protein, zinc finger protein PLAGL2, and finally novel zinc finger protein. None of them resulted as the causative gene but several protein variants and DNA polymorphisms have been identified. These data exclude the role of the above mentioned genes in causing CDA II and add further information in the process of cloning the CDA II gene.
Blood Cells Mol Dis
PMID:Congenital dyserythropoietic anemia type II: exclusion of seven candidate genes. 1266 84

The congenital dyserythropoietic anemias are a heterogeneous group of disorders characterized by anemia and ineffective erythropoiesis. Congenital dyserythropoietic anemia type I (CDA1) can present in utero with hydrops fetalis, but more often it presents in childhood or adulthood with moderate macrocytic anemia, jaundice, and progressive iron-overload. CDA1 is inherited in an autosomal recessive manner, with biallelic pathogenic variants in CDAN1 or C15orf41. This case report documents a severe fetal presentation of CDA1 where we identified two novel compound heterozygous mutations in CDAN1 and describes the associated pathologic findings and levels of iron-regulatory proteins hepcidin, erythroferrone, and GDF15.
Blood Cells Mol Dis 2018 07
PMID:Fetal presentation of congenital dyserythropoietic anemia type 1 with novel compound heterozygous CDAN1 mutations. 2959 85