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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human cellular DNA fragments from cells of normal subjects and patients with thalassemia obtained by restriction enzyme digestion were analyzed for their globin gene content. The fragments were separated on agarose gels, transferred to nitrocellulose filters, hybridized to globin [(32)P]cDNA, and radioautographed. One to ten picograms of globin gene sequences were detectable. With EcoRI digestion, eight to nine cellular DNA fragments were found to contain globin genes. Three of these contained beta-like gene sequences assayed with beta globin cDNA probe. One beta-like fragment was absent in DNA from a homozygous subject for hemoglobin Lepore. Two of the three beta gene-containing fragments present in normal DNA were absent in DNA from a patient with hereditary persistence of fetal hemoglobin. The same two fragments containing beta-like genes were absent from deltabeta thalassemic DNA and one new fragment containing beta-like genes was found. Together with results obtained by hybridization of these DNAs in solution, the data are consistent with deletion of specific restriction human DNA fragments in subjects with these disorders and a greater deletion of beta-like gene sequences in subjects with hereditary persistence of fetal hemoglobin than in those with deltabeta thalassemia.
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PMID:Changes in restricted human cellular DNA fragments containing globin gene sequences in thalassemias and related disorders. 27 14

Minor fetal hemoglobins in red cell hemolysates of newborn and adults with elevated levels of Hb F have been separated and quantitated by Biorex 70 column chromatography. In addition to Hb F1, other minor hemoglobin zones eluting before F1, pre-F1, and after F1, post-f1 have been observed. The relative amounts of the two pre-F1 zones and F1 are higher in the red cells of adults with 97--100% Hb F (homozygous hereditary persistence of fetal hemoglobin, homozygous deltabeta-thalassemia and homozygous beta0-thalassemia) than in the red cells of an adult with homozygous beta+-thalassemia with 66% Hb F, a child with a trisomy-D-13 having 38% Hb F, and in two newborn. Hb F was glycosylated in vitro with [14C]glucose or [14C] glucose 6-phosphate, and was acetylated using chicken reticulocyte lysate or a crude acetyltransferase preparation isolated from the same lysate with [14C]acetyl-CoA as substrate. Chromatographic analyses indicated that the Hb F1 zone can be formed both by glycosylation and acetylation of Hb F, and that pre-F1 zones can be products of the reaction of Hb F with phosphorylated glycolytic intermediates. Biosynthesis of minor hemoglobins in reticulocytes was studied with [14C]leucine in the presence and absence of cycloheximide and by pulse-chase. The resulting data indicate that Hb F1 synthesis is dependent upon Hb F synthesis and that the posttranslational modification may take place at an early stage in Hb F synthesis.
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PMID:On the chromatographic heterogeneity of human fetal hemoglobin. 42 12

A further study of the Tgamma-chain in a variety of conditions has revealed its presence in the cord bloods of ethnic groups previously unstudied. Heterozygous newborn average 17-19% Tgamma-chain while the mean value in four presumed homozygotes was 31%. The Tgamma-chain is readily detectable in beta-thalassemia of various ethnic groups (although infrequent in Blacks) as well as in deltabeta-thalassemia. Studies of a few families have provided an opportunity to determine whether or not certain individuals are heterozygous or homozygous for the Tgamma-gene. The Tgamma-chain has not been detected in the human fetal hemoglobin that is synthesized in increased amounts in persons with the hereditary persistence of fetal hemoglobin. Although the Tgamma-chain is detectable in sickle cell anemia, its frequency appears to be lower than in normal individuals. By focusing upon the relationship of the percentage of Tgamma-chain to the sources of human fetal globulin from determinants in cis and in trans, the conclusion has been reached that the Tgamma-chain is the product of a mutant Agamma-locus which should be named the TAgamma-chain.
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PMID:Further studies of the frequency and significance of the Tgamma-chain of human fetal hemoglobin. 42 52

Routine laboratory investigations of hemoglobinopathies include Hb electrophoresis for abnormal hemoglobins, determination of Hb A2 (alpha 2 delta 2) for beta-thalassemia traits, staining for Hb H (beta 4) inclusions for alpha-thalassemia traits and estimation of Hb F (alpha 2 lambda 2) for the presence of hereditary persistence of fetal hemoglobin genes (HPFH). Frequently, analytical column chromatography and alpha/beta hemoglobin chain synthesis are used in the studies of more complicated hemoglobinopathies. This communication outlines the procedures used in this laboratory for the diagnosis of a case of Hb CC-alpha-thalassemia.
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PMID:Laboratory diagnosis of HB CC-alpha-thalassemia. 51 45

We applied a recently developed and more direct technic to diagnose thalassemia syndromes associated with deletion of particular globin structural genes and to assess a fetus at risk for one of those conditions, deltabeta-thalassemia. The method allows assessment of the globin genes present in total cellular DNA and is applicable to amniotic-fluid cell DNA. Cellular DNA fragments produced by cleavage using two specific restriction endonucleases are separated on the basis of size by agarose-gel electrophoresis, and the distribution of specific sequences among the DNA fragments determined by molecular hybridization. We observed the total deletion of alpha-globin genes in homozygous alpha-thalassemia (hydrops fetalis with hemoglobin Bart's) and the deletion of particular beta and beta-like sequences in cases homozygous for hereditary persistence of fetal hemoglobin and deltabeta-thalassemia. Analysis of amniotic-fluid cell DNA from a fetus at risk for deltabeta-thalassemia demonstrated the feasibility of these improved methods for antenatal diagnosis. The molecular studies confirmed the diagnosis predicted by analysis of fetal blood and established at birth.
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PMID:Application of endonuclease mapping to the analysis and prenatal diagnosis of thalassemias caused by globin-gene deletion. 66 90

We have studied a 41-year-old black male with the simultaneous occurrence of hereditary persistence of fetal hemoglobin (HPFH) and beta-thalassemia, and his two postadolescent sons, each heterozygous for one of the traits. The son heterozygous for beta-thalassemia had an elevated Hb A2, but the index case did not. The data from this pedigree indicate that the delta-allele trans to the beta-thalassemia gene was reponsible for the increased delta-chain production. Evidence from other cases of combination HPFH and beta-thalassemia indicates that regulation of the beta- and delta-chain production in beta-thalassemia is heterogeneous with respect to mechanism.
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PMID:Regulation of the beta- and delta-hemoglobin genes. A family with hereditary persistent fetal hemoglobin and beta-thalassemia. 82 85

DNA has been prepared from peripheral blood or cultured skin fibroblasts obtained from three Sicilian and one Greed deltabeta-thalassemia homozygotes. Globin-gene analysis was carried out using a cDNAbeta probe, and the results indicate that deltabeta-thalassemia has arisen from a deletion of the beta-globin genes. A similar result was obtained using DNA prepared from cultured skin fibroblasts from an individual homozygous for the Negro form of hereditary persistence of fetal hemoglobin (HPFH). In both cases, the deletion has spared the Ggamma and Agamma loci directing the gamma chains of hemoglobin F, but it has not been possible to demonstrate any difference between the size of the deletion involved in the production of delta-beta-thalassemia and that which gave rise to HPFH. These experiments provide further direct evidence that deletions of critical areas of the gamma-delta-beta gene cluster result in persistent gamma chain synthesis in adult life.
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PMID:Delta-beta-thalassemia is due to a gene deletion. 97 41

The syndrome thalassemia intermedia can be the clinical expression of heterozygosity for different tyes of thalassemia, beta-thalassemia and hereditary persistence of fetal hemoglobin, beta-thalassemia and Hb-Lepore, and in blacks it may even represent a true beta-thalassemia homozygote. This report describes thalassemia intermedia in a white male due to beta-thalassemia and an unstable hemoglobin. Chain-synthesis studies showed an excess of alpha-chain production over beta-chain production in the propositus and his mother but balanced chain synthesis in the clinically normal father, who is heterozygous for the unstable hemoglobin. The unstable hemoglobin was found to be beta14 (A11) Leu leads to Pro, which has previously been described in a clinically normal African woman, and named Hb-Saki. This hemoglobin is not distinguishable from Hb-A on routine electrophoresis at alkaline or acid pH and tests for unstable hemoglobins are necessary for its detection. The increasing list of such hemoglobin variants and previous cases of heterozygosity for beta-thalassemia and unstable hemoglobins are reviewed.
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PMID:Thalassemia intermedia caused by heterozygosity for both beta-thalassemia and hemoglobin Saki [beta 14 (A11) Leu replaced by Pro]. 99 17

The percentages of minor adult hemoglobin (%Hb A2) in hemolysates and G gamma-globin chain (%G gamma) in fetal Hb (Hb F) of 15 individuals with elevated Hb F levels (2.0-11%) among 11,000 healthy Japanese adults were examined. Most of them might be carriers for the determinants of hereditary persistence of fetal hemoglobin. Subjects with less than 1.3% Hb A2, some of whom might be also carriers for delta-thalassemia determinants, had high G gamma values (54-70%). Those homozygous for a subhaplotype [+-----] 5' to the delta-globin gene had low to mid G gamma values (7-49%), while those homozygous for [-++-++] possessed high G gamma values (60-85%), but varied Hb F values (3.1-11%). Those heterozygous for the presence of the XmnI site 5' to (-158 bp to the cap site of) the G gamma-globin gene had mid to high G gamma values (53-65%). Factors for the high or low G gamma-globin gene expression in the Japanese adult with elevated Hb F level should be highly associated with a subhaplotype [-++-++] or [+-----], respectively.
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PMID:%Hb A2, %Hb F, %G gamma values and the haplotypes in the beta-globin gene cluster in Japanese adults with elevated Hb F. 138 Sep 45

We report microchromatographic measurement of fetal hemoglobin (HbF) proportions in a 36-year-old African-American multigravida woman. At 34 weeks she delivered a 630-g male infant who subsequently did well. Hemoglobin electrophoresis of the hemolysate revealed nearly 100% HbF without HbA, an extremely unusual naturally occurring sample. Family studies revealed a combination of hereditary persistence of fetal hemoglobin (HPFH) and beta zero-thalassemia minor. Southern blot technique confirmed heterozygous alpha 2 thalassemia and HPFH but failed to identify the beta thalassemic lesion. The absence of HbA and the very high amounts of HbF led us to measure HbF by several methods to confirm the accuracy of microchromatography of HbF at values approaching 100%. HPLC revealed a 14% F1 suggestive of microchromatographic underestimation due to glycated HbF. We conclude that cation-exchange microchromatography and the Betke method of alkali denaturation underestimate HbF values as they approach 100% and do not recommend these procedures in this rare situation.
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PMID:Failure of microchromatographic measurement of fetal hemoglobin in beta zero thalassemia-hereditary persistence of fetal hemoglobin. 138 20


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