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)

In previous studies of patients with beta thalassemia, mRNA extracted from reticulocytes in peripheral blood when added to cell-free systems reproduces the deficient beta-chain synthesis characteristic of intact cells. The present studies with specific probes for alpha and beta mRNA were designed to decide whether the decreased beta mRNA activity is due to the presence of abnormal or reduced beta globin mRNA in these cells. Purified alpha and beta complementary DNAs (cDNAs) have been synthesized with RNA-instructed DNA polymerase; alpha and beta mRNAs isolated from heavy (beta-producing) and light (alpha-producing) polyribosomes of rabbit reticulocytes were used as templates. Each of the cDNAs is more than 80% pure by the criterion of biological activity. The alpha cDNA labeled with [(32)P]dCTP and the beta cDNA labeled with [(3)H]dCTP have been added simultaneously to reaction mixtures containing various concentrations of mRNA from thalassemic and nonthalassemic subjects. The extent and rate of hybridization were determined, permitting a comparison of relative alpha and beta mRNA content in the same annealing mixture. In six nonthalassemic patients, relatively equal amounts of hybridizable alpha and beta mRNA appear to be present. In five of seven patients with beta-thalassemia, significantly decreased amounts of beta mRNA compared to alpha mRNA can be demonstrated. In two patients with Hemoglobin H disease, there is a decreased amount of alpha mRNA compared to beta mRNA.
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PMID:Decreased globin messenger RNA in thalassemia detected by molecular hybridization. 412 7

In two black families with the hereditary persistence of fetal hemoglobin (HPFH) gene there are eight A-F heterozygotes and two double heterozygotes for sickle cell trait and HPFH. These patients are clinically asymptomatic and have homogeneous acid elution smears. Measurement of globin chain synthesis in peripheral blood demonstrates balanced production of a alpha and non-alpha (beta plus gamma) chains. In these patients, the balance is achieved by increased gamma globin production and increased activity of the remaining beta globin allele. In two patients, one A-F and the other S-F there is also balanced globin synthesis in the bone marrow. In a double heterozygote for HPFH and beta-thalassemia, anemia (Hb: 11.5 g/100 ml) is associated with a moderate degree of globin chain imbalance. There is a correlation between balanced globin chain synthesis and the absence of anemia in patients with HPFH.
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PMID:Balanced globin chain synthesis in hereditary persistence of fetal hemoglobin. 484 53

Members of a Black family from Georgia who were investigated for the first time in 1960 and several times thereafter were reinvestigated through DNA restriction endonuclease analyses and haplotyping, while the gamma chain heterogeneity of the Hb F was reevaluated using a newly developed HPLC procedure. Four different abnormalities were present. (a) Heterozygosity for G gamma A gamma-HPFH type II characterized by a large deletion involving the delta and beta globin genes with a 5' end within the psi beta gene. (b) Heterozygosity for an -epsilon-G gamma-G gamma-psi beta-delta-beta S-chromosome, thus carrying a beta S globin gene and two G gamma genes instead of one G gamma and one A gamma gene. (c) Heterozygosity for an -epsilon-G gamma-A gamma T-psi beta-delta-beta S-chromosome, carrying the beta S globin gene and an allele of the A gamma (or A gamma I) gene. These three chromosomes occurred in combination with each other, resulting in SS and S-HPFH conditions, and with a normal -epsilon-G gamma-A gamma-psi beta-delta-beta A-chromosome resulting in the HPFH and Hb S heterozygosities. The presence of the -G gamma-G gamma- and -G gamma-A gamma T-chromosomes in the one SS patient was responsible for the high G gamma value (average 75%), 25% A gamma T chain, and for the absence of the A gamma I chain. (d) An alpha-thalassemia-2 heterozygosity in one member.
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PMID:Hemoglobin abnormalities in a black family with HB S, hereditary persistence of HB F, and a gamma chain variant; a reevaluation through gene mapping. 608 52

The prevalence of the BamH I site 3' to the beta globin gene in Chinese people was determined in 123 normal subjects, 40 patients with heterozygous beta thalassaemia, and 25 patients with homozygous beta thalassaemia. The site was present in 71.1% and absent in 28.9% of the chromosomes carrying normal beta genes. All 25 patients with beta thalassaemia major had the site. This BamH I polymorphism may be used for prenatal diagnosis in about 29% of the pregnancies at risk.
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PMID:BamH I polymorphism in the Chinese: its potential usefulness in prenatal diagnosis of beta thalassaemia. 609 39

The genetic factors responsible for the relatively mild clinical phenotypes of some cases of homozygous beta zero thalassaemia (thalassaemia intermedia) in Sardinia have been evaluated. The frequency of deletion forms of alpha thalassaemia was higher in patients with thalassaemia intermedia (6/8) than in those with thalassaemia major (6/17). The beta globin gene clusters were also studied, first to determine whether there were any rearrangements of the gamma genes, and second to see whether the restriction fragment length polymorphism patterns (haplotypes) of the two groups of patients were similar. The structure of the gamma genes was normal in all the patients with the single exception of a thalassaemia major patient with a triplicated gamma gene arrangement. The beta globin gene cluster haplotypes of the two groups of patients were not significantly different. However, the frequency of the various haplotypes in the thalassaemic as compared to the normal (beta A) chromosomes was different. This finding is of potential value in the antenatal diagnosis of homozygous beta thalassaemia in this population.
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PMID:Globin gene mapping studies in Sardinian patients homozygous for beta zero Thalassaemia. 609 22

Twenty-six DNA samples from individuals either heterozygous or homozygous for beta thalassemia were analyzed by restriction endonuclease digestion, agarose gel electrophoresis, and Southern blot analysis to define DNA fragments containing portions or all of the beta globin gene. A total of twenty-seven genes affected by a beta thalassemia mutation and twenty-seven genes affected by a beta thalassemia mutation and twenty-two normal beta globin genes were examined in Italian, Greek, or Asian individuals. With all four restriction endonucleases used, the fragments generated from DNA of thalassemic individuals were identical to those found in DNA from normal. Thus, gross rearrangement or deletion within the genomic region containing the beta globin gene is not characteristic of mutations which cause a thalassemia. A third patient homozygous for pancellular hereditary persistence of fetal hemoglobin was shown to have complete deletion of the delta and beta globin genes.
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PMID:Analysis of globin gene structure in patients with beta thalassemia by restriction endonuclease mapping. 616 67

Twelve patients with homozygous beta-thalassemia from Azerbaijan are described. From biosynthetic studies, we have established that seven children had beta +-thalassemia, while five had beta 0-thalassemia. In six patients with beta +-thalassemia a close correlation has been found between alpha/beta globin chain synthesis and alpha/beta mRNA content determined by molecular hybridization. In one case of beta +-thalassemia no such correlation has been observed. It was possible to study nuclear and cytoplasmic RNA from spleen erythroid cells in one of the patients. alpha/beta globin RNA ratio was 5 in both cases, suggesting the possibility of a defect in beta-globin gene transcription. In cases of beta 0-thalassemia, heterogeneity of the relative content of beta-globin mRNA was revealed: either it is found in considerable amounts, or it is completely absent. Mapping of DNA from two beta-thalassemic patients by restriction enzymes yielded a normal pattern for the beta-globin gene region.
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PMID:[Molecular causes of thalassemia. III. Molecular genetic variants of beta-thalassemia in Azerbaijan]. 618 Sep 57

We have characterized 14 patients in 10 families with a mild form of homozygous beta thalassemia which has not been previously well defined. As these patients originate from a small area of northern Portugal we propose to call this beta + thalassaemia--Portuguese type. Clinically, the homozygotes range from asymptomatic to thalassaemia intermedia and they are characterized by low levels of HbF, less than 20%, indicating only a mild deficit in beta globin production. Heterozygotes are indistinguishable from those with the more common types of beta thalassaemia as regards red cell morphology, haemoglobin analysis and globin chain synthesis studies. Globin gene mapping excluded the presence of alpha thalassaemia in these patients and demonstrated no abnormalities in the beta-like globin gene cluster. Restriction enzyme site polymorphisms around the beta gene cluster are identical on both chromosomes in all of the homozygotes, confirming their homogeneity.
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PMID:Beta + thalassemia--Portuguese type: clinical, haematological and molecular studies of a newly defined form of beta thalassaemia. 618 7

Comparisons were made of drug-induced oxidation of purified hemoglobins A, S, E, and F. Repetitive spectral scans of reaction mixtures containing menadione showed that Hb E was the most reactive and Hb F was the least reactive of the hemoglobins studied. Hb E oxidation was only slightly faster than normal, but it produced much larger relative quantities of low-spin ferric hemoglobin (hemichromes). Hb F oxidation was considerably slower than normal but produced normal amounts of hemichromes relative to methemoglobin. Precipitation occurred in the order E greater than S greater than A greater than F. The abnormally slow rate of Hb F oxidation was even more striking when the oxidant was acetylphenylhydrazine (APH), and the sensitivity of the reaction to catalase was severely diminished. These hemoglobins thus exhibit entirely different reaction profiles during drug-induced oxidation. The amino acid substitution in Hb E alters the globin tertiary structure, so that hemichromes can more readily form, whereas the decreased susceptibility to oxidative denaturation of Hb F appears related to the absence of a site that normally reacts with hydrogen peroxide to increase oxidation rate. Such Hb F stability is consistent with the mild phenotypic expression of doubly heterozygous beta-thalassemia/HPFH and Hb S/HPFH. The role of Hb E instability in altered red cell morphology relative to the thalassemia-like deficit of beta globin mRNA has not been entirely resolved. Nevertheless, the clinical repercussions of the abnormal properties of Hb E are mild, and they may be involved with the prevalence of this hemoglobin in Southeast Asia as a balanced polymorphism in which the advantage to heterozygotes is, as yet, unclear.
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PMID:Differences in the reaction sequences associated with drug-induced oxidation of hemoglobins E, S, A, and F. 619 77

In Sardinia the common form of beta thalassemia is a beta 0 thalassemia due to a nonsense mutation at codon 39. delta beta 0 Thalassemia is rare in Sardinia and is associated with increased production of hemoglobin F of the A gamma type. In this study we used a synthetic oligomer assay and detected the beta 39 nonsense mutation on the delta beta 0 thalassemia chromosome. Hence at least two different mutations have occurred on this chromosome; one that increases A gamma globin synthesis and another that silences the beta globin gene.
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PMID:Multiple mutations produce delta beta 0 thalassemia in Sardinia. 619 20


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