Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From March to August 1984, 26 patients with hereditary hemolytic anemia in northeastern Ohio developed acute, profound red cell aplasia. The patients included 14 males and 12 females 2 to 23 years old, with sickle cell anemia (20 cases), hemoglobin SC-disease (4 cases), sickle-beta-thalassemia (1 case), or hereditary spherocytosis (1 case). All had an acute onset of severe reticulocytopenia and anemia and prodromal symptoms of illness including fever, abdominal symptoms, headache, and arthralgias. Twenty-two received transfusions. Reticulocytosis occurred spontaneously within 2 to 14 days of presentation. In five acute-phase sera, 10(8) to 10(12) viral particles/mL were detected by electron microscopy. Human parvovirus B19 DNA was demonstrated in high concentration by hybridization in the same five acute-phase sera and in low concentration in sera of eight additional patients. The five highly viremic sera inhibited erythroid colony formation in vitro. B19-specific IgM was detected in sera of 24/26 patients, and B19-specific IgG in 21 of 22 patients tested. Our results indicate that human parvovirus B19 was the etiologic agent in this large epidemic of life-threatening acute red cell aplasia in patients with hereditary hemolytic anemia.
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PMID:Human parvovirus B19-induced epidemic acute red cell aplasia in patients with hereditary hemolytic anemia. 300 91

Two children with typical clinical and haematological features of monosomy 7 myeloproliferative syndrome are presented. Both children displayed decreased production of beta-globin chains and unbalanced high alpha/non-alpha synthetic ratios similar to those characteristic of homozygous beta-thalassaemia. These provide further evidence for the involvement of the erythroid line as part of the malignant clone, indicating neoplastic transformation of a pluripotential stem cell in this disease.
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PMID:Disturbed patterns of globin chain synthesis in childhood monosomy 7 myeloproliferative syndrome. 335 95

5-Aminolaevulinic acid (ALA) synthase activity was measured in highly purified preparations of age-matched human erythroblasts. Enzyme activity in immature normoblasts was four-fold higher than that found in late orthochromatic normoblasts. ALA synthase activity in the immature erythroblasts in primary acquired sideroblastic anaemia (PASA) was reduced and remained unchanged during further erythroid differentiation. The pattern of erythroblast ALA synthase activity in two patients with congenital dyserythropoietic anaemia (CDA) and in one patient with beta-thalassaemia intermedia was similar to that found in PASA. This study has clearly demonstrated reduced erythroblast ALA synthase activity in PASA but has also found reduced enzyme activity in conditions in which ring sideroblasts are not prominent. This would suggest that haem synthesis is abnormal in PASA but that reduced erythroblast ALA synthase activity does not inevitably lead to ring sideroblast formation.
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PMID:5-Aminolaevulinic acid synthase activity in developing human erythroblasts. 339 Mar 96

We have identified a beta-thalassemia gene that carries a novel nonsense mutation in a Chinese patient. This mutation, a G to T substitution at the first position of codon 43, changes the glutamic acid coding triplet (GAG) to a terminator codon (TAG). Based on oligonucleotide hybridization studies of 78 Chinese and Southeast Asian beta-thalassemia chromosomes, we estimate that this mutation accounts for a small minority of the beta-thalassemia mutations in that population. Study of the expression of this cloned gene in a transient expression system demonstrated a 65% decrease in levels of normally spliced mutant beta-globin mRNA. However, the study of reticulocyte RNA isolated from an individual heterozygous for this mutation demonstrated a total absence of this mutant mRNA in vivo. The basis for this big discrepancy between the level of accumulated mRNA in vivo and in vitro is probably the result of differences in the stabilities of the mutant mRNA in erythroid cells.
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PMID:New amber mutation in a beta-thalassemic gene with nonmeasurable levels of mutant messenger RNA in vivo. 340 16

Three Japanese individuals with homozygous delta zero-thalassemia from different families were the subjects of molecular genetic analysis. They were homozygous for seven polymorphic sites in the beta-globin gene cluster. Nucleotide sequence analysis of the delta-globin gene cloned from each patient revealed a single nucleotide substitution (T-C) 77 base pairs 5' to the cap site, just upstream of the CCAAC box of the delta-globin gene. When introduced into COS cells, the gene was expressed at normal levels with proper processing of RNA. These results suggest that the complete suppression of delta-globin chain synthesis in these patients is not due to a defective promoter, a defective RNA processing or a chain terminator mutation, but rather to impaired regulation of gene expression specific to erythroid cells. The region around the CCAAC box may have a significant role in expression of the delta-globin gene in erythroid cells.
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PMID:A delta-globin gene derived from patients with homozygous delta zero-thalassemia functions normally on transient expression in heterologous cells. 347 64

The transient fetal-like erythropoiesis which appears during recovery from bone marrow transplantation has now been examined at the level of erythroid progenitor cells. A 7-year-old boy with beta +-thalassaemia major was studied during engraftment from his beta-thalassaemia trait sister. Hb F and i antigen rose as expected. Macrocytosis never developed, but red cell size distribution became very heterogeneous. Bone marrow CFU-E and BFU-E were detected by 30 d, prior to the appearance of reticulocytes. Marrow erythroid progenitor cell numbers were normal by 146 d, while those in the blood became normal by 360 d. After transplantation globin synthesis ratios in erythroid colonies were diagnostic of thalassaemia trait, indicating engraftment. Individual erythroid colonies derived from both blood and marrow at all times during reconstitution showed no correlation of G gamma and gamma. Thus the fetal-like stress erythropoiesis of marrow expansion following transplantation was derived from adult and not fetal progenitor cells.
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PMID:Adult 'fetal-like' erythropoiesis characterizes recovery from bone marrow transplantation. 352 55

Patients with beta zero thalassemia arising from premature terminator codon mutations in the gene for beta globin do not produce beta globin protein; these individuals also exhibit a decreased amount of beta globin mRNA in their erythroid cells. The absence of beta globin protein is readily explained by the inability of the beta zero-39 mRNA to be translated. The decrease in beta globin mRNA has been attributed to either decreased cytoplasmic stability of the nontranslatable decreased cytoplasmic stability of the nontranslatable mRNA or to an undefined nuclear lesion. To compare directly the relative stabilities of normal and beta zero-39 thalassemic globin transcripts, we prepared normal and thalassemic beta globin pre-mRNAs and mRNAs using cloned DNA templates and the SP6 promoter-polymerase system. The stability of the transcripts was assessed by incubation in various cell-free extracts. Our results indicate that although the stabilities of the beta globin transcripts varied considerably from one extract to another the stabilities of the beta zero-39 thalassemic pre-mRNAs and mRNAs were equal to those of normal beta globin mRNAs in every extract tested.
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PMID:Equal stabilities of normal beta globin and nontranslatable beta0 -39 thalassemic transcripts in cell-free extracts. 359 68

Recent studies show that the region of DNA brought into close proximity to the fetal gamma-globin genes in deletional forms of hereditary persistence of fetal hemoglobin (HPFH) is selectively hypomethylated (and presumably active) in normal erythroid tissue. This region is normally located approximately 100 kilobases (kb) 3' to the fetal genes. The continued expression of fetal hemoglobin in adult life in these forms of HPFH has been ascribed to the effect of this erythroid-specific region in altering local chromosomal structure and allowing transcription. Because transcriptional activity is often associated with hypomethylation, we have examined the methylation status of the gamma-globin genes and the truncated psi beta gene on the HPFH chromosome to determine whether juxtaposition of this erythroid-specific region results in a generalized hypomethylation of the globin gene region upstream of the deletion breakpoint. Genomic DNA purified from nucleated red blood cells (nRBC) from a patient with HPFH-2/beta O thalassemia was digested with Msp I or Hpa II, and the methylation pattern determined on the HPFH chromosome by using secondary cleavage with restriction enzymes which span the deletion breakpoint. These studies show that in nRBC the HPFH-2 chromosome is hypomethylated in the 3'-juxtaposed region (3'JR) and in the region of the gamma-globin genes. In contrast, Msp I sites near the truncated psi beta-globin gene remain methylated, suggesting that only a subset of CpG sites upstream from the 3'JR become hypomethylated in HPFH-2. This subset of sites corresponds to those which are normally hypomethylated when fetal genes are active. The continued high level of fetal globin expression is, therefore, not associated with a generalized hypomethylation upstream from the deletion junction.
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PMID:DNA methylation in hereditary persistence of fetal hemoglobin (HPFH-2). 360 70

The adequacy of tissue iron supply was examined with ferrokinetic techniques in subjects with decreased plasma iron concentration and in subjects with a normal plasma iron concentration but with increased tissue iron requirements. The competition by transferrin receptors for diferric vs monoferric transferrin was measured in eight normal persons and eight with iron deficiency. There was a highly significant (P less than 0.001) decrease in receptor preference for diferric transferrin in subjects with iron deficiency, indicating an insufficient amount of iron-bearing transferrin to saturate tissue receptors. The adequacy of the plasma iron supply was also examined by determining the number of iron-bearing transferrin molecules with receptors at normal and elevated plasma iron concentrations. Significant increases were found at the higher plasma iron concentration, not only in patients with iron deficiency, but also in patients with sickle cell anemia and thalassemia. Furthermore, the increase in the latter two groups was shown to be proportional to the degree of erythroid hyperplasia. These data indicate that tissue iron supply must be evaluated in terms of both plasma iron supply and erythropoietic requirements and that a relative iron deficiency is frequent in patients with erythroid hyperplasia.
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PMID:Adequacy of iron supply for erythropoiesis: in vivo observations in humans. 368 Nov 15

The two human alpha-globin genes, alpha 1 and alpha 2, are coexpressed in normal erythroid cells and encode identical alpha-globin protein products. Based upon genetic studies, it has been assumed that these two adjacent and highly homologous genes are equally expressed. In previous studies we have, however, demonstrated that the alpha 2 gene encodes a 2-3-fold higher steady state level of mRNA than the alpha 1 gene. In the present study, we monitor the relative levels of protein production from these two loci by quantitating the synthesis of specific alpha-globin structural mutants encoded by each alpha-globin gene. These values are then used to infer the relative contributions of the normal alpha 1 and alpha 2 loci to total alpha-globin production. The results of eight separate studies, each based upon a different alpha-globin structural mutant mapped to either the alpha 1 or the alpha 2 locus, are internally consistent. The data demonstrate that the alpha 2 gene encodes 2-3-fold more protein than the alpha 1 gene. These results suggest that the human alpha-globin gene cluster contains a major and a minor locus. The dominant expression of the alpha 2 gene predicts a greater impact of mutations at this locus, in comparison to mutations at the alpha 1 locus, in the generation of the alpha-thalassemia phenotype.
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PMID:Human alpha-globin gene expression. The dominant role of the alpha 2-locus in mRNA and protein synthesis. 377 77


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