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

We carried out alpha-globin gene analysis by restriction endonuclease mapping in 91 Sardinians with homozygous transfusion-dependent beta 0-thalassemia and correlated the clinical findings with the alpha-globin genotype. In patients (n = 6) with deletion of two alpha-globin structural genes, disease onset and transfusion dependence occur later than in those (n = 50) with a full complement of alpha-globin genes. There was no statistically significant difference in the group of patients (n = 35) with deletion of only one alpha-globin gene. Patients with deletion of two alpha-globin genes had significantly higher Hb A2 levels than those with a full complement of alpha-structural genes and those with deletion of a single alpha-globin gene. From this and other studies, it seems that the deletion of two alpha-globin structural genes may convert the common severe clinical picture associated with homozygous beta 0-thalassemia to milder forms, ranging from a later occurring but still transfusion-dependent type to a non-transfusion-dependent form.
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PMID:Molecular mechanism accounting for milder types of thalassemia major. 619 Oct 17

Restriction endonuclease and analyses of DNA from a known Hb F-Yamaguchi heterozygote and three of his relatives have shown a deletion of about 5 kb, which includes one of the gamma genes. This abnormality is similar to the G gamma-thalassemia described recently [4] and is probably caused by an unequal crossing over between-G gamma- and -A gamma T-genes. The abnormal-G gamma A gamma T-X-(X = Asp leads to Asn at gamma 80) hybrid gene produces the gamma-Yamaguchi chain at a level usually seen for G gamma chains only.
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PMID:HB F-Yamaguchi (gamma 75Thr, gamma 80Asn, gamma 136Ala) is associated with G gamma-thalassemia. 619 5

Clinical, haematological and gene mapping data are presented on two South African cases of sickle-cell anaemia. Both individuals, who are siblings, have experienced a very mild clinical course. Restriction endonuclease analysis showed that 1 sibling was homozygous for alpha+-thalassaemia (genotype alpha-/alpha-), whereas the other had a full complement of alpha-globin genes. Both showed markedly elevated levels of Hb F. The maintenance of high levels of Hb F is the most probable explanation for the moderate clinical expression of the disorder in these patients.
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PMID:Mild clinical course in two South African cases of sickle-cell anaemia. 620 89

In this study, we have correlated the hematological phenotype of 56 Sardinian beta o-thalassemia heterozygotes with their alpha-globin genotype as defined by restriction endonuclease mapping. We found that the coinheritance of the deletion of one alpha-globin and, more obviously, two alpha-globin genes tend to normalize the thalassemia-like hematological phenotype commonly associated with the beta o-thalassemia carrier state. On the other hand, the association of the deletion of three alpha-globin genes caused a more severe phenotype. By globin chain synthesis analysis, those beta o-thalassemia heterozygotes with the (-alpha/alpha alpha) alpha-globin genotype had less deficiency of beta-chain synthesis than did those with the normal alpha-globin genotype (alpha alpha/alpha alpha). In heterozygotes with the (-alpha/-alpha) and in those with the (--/-alpha) alpha-globin genotype the imbalance was actually reversed with a mild or marked alpha-chain synthesis excess respectively.
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PMID:Hematological phenotype of the double heterozygous state for alpha and beta thalassemia. 620 59

Restriction endonuclease mapping data are presented for the DNA of a young Indian homozygous patient (and his heterozygous parents) who were identified 10 years ago as having a G gamma-hereditary persistence of fetal haemoglobin (Sukumaran et al, 1972). However, the present results indicate a genetic lesion in these persons which is similar to that observed in another Indian with (A gamma delta beta)0-thalassaemia homozygosity (Amin et al, 1979) and is characterized by two relatively short deletions and an inversion involving the A gamma, delta and beta globin genes (Jones et al, 1981a). Some additional blot hybridization studies have provided further data confirming the deletion-inversion hypothesis.
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PMID:Restriction endonuclease gene mapping studies of an Indian (A gamma delta beta)zero-thalassaemia, previously identified as G gamma-HPFH. 620 82

The alpha-globin genes of five black Americans, two Chinese, and five Filipinos with HbH disease (an alpha-thalassemia state in which there is a single functional alpha gene) were analyzed by restriction endonuclease techniques. All subjects were found to have one chromosome 16, lacking both alpha genes, and another containing a single alpha gene (--/-alpha). Restriction endonuclease patterns of the DNA obtained from all 12 subjects were identical and compatible with unequal crossing-over as the mechanism of origin of the single alpha gene in these individuals.
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PMID:Unequal crossing-over: a common basis of single alpha-globin genes in Asians and American blacks with hemoglobin-H disease. 624 95

Restriction endonuclease mapping permitted identification of a form of beta 0-thalassemia in which a partial deletion of the beta-globin structural gene occurred [Orkin, S. H., Old, J. M., Weatherall, D. J. & Nathan, D. G. (1979) Proc. Natil. Acad. Sci. USA 76, 2400-2404]. To analyze its structure more directly, this abnormal human gene has now been cloned in bacteriophage lambda gtWES. Restriction mapping of the cloned gene and of a normal beta-globin gene contained in the phage H beta G1 confirmed previous findings regarding the presence of a deletion toward the 3' end of the gene but could not establish its position more accurately. Electron microscopy of the hybrid of the beta-thalassemia gene with globin RNA (R-loop analysis) provided unequivocal evidence for a deletion with the beta-globin structural gene. Hybridization of restriction fragments of the mutant gene with homologous fragments of H beta G1 (heteroduplex analysis) revealed a continuous, internal deletion of about 0.6 kilobase of DNA in the mutant gene and permitted its localization within the beta-globin gene region. This deletion removed the terminal third of the large intervening sequence within the beta-globin gene, the entire 3' coding block (extending from codon 105 to the end of the gene), and approximately 150 base pairs of DNA past the end of the normal globin gene.
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PMID:Cloning and direct examination of a structurally abnormal human beta 0-thalassemia globin gene. 625 66

In order to assess the applicability of multiple restriction endonuclease analyses of amniocyte DNA to the prenatal diagnosis of beta-thalassemias in general, we studied 12 consecutive couples at risk. DNA of both members of the 12 couples and a previous offspring of each was analyzed for the presence of 4 polymorphic restriction endonuclease sites: the Hpa I site 3' to the beta-globin gene, the Hind III site in the G gamma gene, the Hind III site in the A gamma gene, and the Bam HI site 3' to the beta-gene. Linkage disequilibrium between these sites and beta A or beta thal genes was not found, presumably due to the heterogeneity of beta thal genes. However, the high frequency of polymorphism at these sites allowed differentiation of beta A-bearing chromosomes from beta thal or beta S-bearing chromosomes in both members of 6 couples. In these couples, complete prenatal diagnosis by linkage analysis of amniocyte DNA would be possible. In the remaining 6 couples, beta A and beta thal chromosomes could be discriminated in one member. In about 50% of the pregnancies of these couples, exclusion of beta-thalassemia is possible by this analysis. These data suggest that when linkage analysis of polymorphic restriction endonuclease sites is carried out, prenatal diagnosis of beta-thalassemia states can be accomplished by amniocentesis alone in 75% of pregnancies at risk.
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PMID:Prenatal diagnosis of beta-thalassemias by amniocentesis: linkage analysis using multiple polymorphic restriction endonuclease sites. 625 93

The structure and organization of the human globin genes at the nucleotide level has been established by restriction endonuclease digestion of cellular DNA, and by the isolation and purification of these genes in phage vectors. With this approach it has been possible to define alterations at the DNA level resulting in a group of inherited diseases of man known as the thalassemia syndromes, and related disorders. Combined with other known genetic and biochemical data, these studies provide a framework for understanding the pathogenesis of these disorders at the molecular level.
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PMID:The molecular basis of disorders of human hemoglobin synthesis. 625 9

Six patients and their parents from five different families with Hb H have been evaluated clinically and hematologically. Previous studies using restriction endonuclease mapping technique indicated that alpha-thalassemia determinants in these cases are heterogeneous. Only one of the five cases have the usual genotype for Hb H, which is characterized by an alpha-DNA-specific fragment of 20 kb long by Eco RI digestion. Three cases from two different families have Hb H disease with alpha-specific DNA fragments of 22.5 kg/2.6 kg long; and the other two have alpha-specific DNA fragments of 20 kb/2.6 kg long, in Eco RI digestion of the cellular DNA. The hematological examination of the parents suggests that the alpha-thalassemia condition associated with the Eco RI fragment of alpha-specific cellular DNA of approximately 22.5 kb long produces an alpha-thal-2-like clinical condition, while the other alpha-thalassemia determinant associated with a fragment 2.6 kg long results in an alpha-thal-1-like clinical condition. The clinical and hematological findings of the cases with 22.5 kb/2.6 kb fragment patterns were more severe than the case with the 20 kb/2.6 kb combination. This study suggests that variation in the clinical and hematological findings among patients with Hb H disease may well reflect a heterogeneity of the genotype combination.
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PMID:Hematological evaluation of patients with various combinations of alpha-thalassemia. 626 90


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