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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemoglobin Pasadena [beta 75(E19)Leu----Arg] was found in a boy who had an acute episode of anemia and rapid splenic enlargement. His father was the only other member of a large family with this hemoglobinopathy. We have used gene mapping techniques for direct identification of the beta-globin gene mutation. To correlate the DNA findings with the structural identification of this variant, we have also performed globin chain separation and analysis of the tryptic peptides using high performance liquid chromatography and secondary ion mass spectral analysis.
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PMID:Hemoglobin Pasadena: identification of the gene mutant by DNA analysis using synthetic DNA probes. 334 4

In this paper we reviewed the different methods presently available for prenatal diagnosis of hemoglobin disorders and the impact of this technology in the control of beta-thalassemia in several Mediterranean populations. The vast majority of the inherited hemoglobinopathies can now be detected in the fetus by amniocyte or trophoblast DNA analysis. alpha-thalassemias, delta beta-thalassemias and gamma delta beta-thalassemias, which are usually caused by a gross structural rearrangement of the DNA, may be directly detected by Southern blot analysis. Only a few beta-thalassemia lesions are caused by gene deletion or affect a restriction recognition site and thus may be directly identified by this method. The major part of beta-thalassemia are due to single nucleotide substitution, small deletion or addition which do not alter a restriction recognition site. These mutations may be directly detected by complementary oligonucleotide probes. Alternatively, when normal or affected children are available, fetal diagnosis may be accomplished by linkage analysis with polymorphic restriction sites. Fetal blood analysis is used at present time for those cases presenting too late in the pregnancy for characterization of the molecular defect and in prospective parents in whom the defect is not known. Introduction of prenatal diagnosis in combination with carrier screening in several mediterranean populations led to a consistent reduction in the incidence of homozygous beta-thalassemia.
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PMID:Prenatal diagnosis of inherited hemoglobinopathies. 354 Feb 10

The overall results of the WHO International Registry for the Prenatal Monitoring of Hereditary Anemias are summarized in Tables 11 and 12. Comparison of data regarding adequacy of samples, and freedom from errors and from fetal losses show that the chance of a couple obtaining a useful result is greater than 90%, whether fetal flood is sampled because the fetus is at risk for a hemoglobinopathy or another disease, or fetal DNA is obtained for globin gene analysis. Each approach serves as a model for the others. Fetal blood sampling technology has been improved because of the need for entirely pure samples for diseases requiring specimens other than red cells. The advances in obtaining fetal cells early in pregnancy and extraction of DNA will soon be applied to diseases other than hemoglobinopathies (such as hemophilias and muscular dystrophies) as molecular probes become available. More than 6000 fetuses have now been examined in utero, 5617 for all hemoglobinopathies using fetal blood or DNA, and 5921 for all disorders using fetal blood (Table 12). The total reported to the Registry by the end of 1983 was 6282 cases. At the moment, the only choices when an affected fetus is detected are termination of the pregnancy, or delivery of a child known to have a serious and sometimes life-threatening illness. However, early diagnosis will lead to early treatment of such infants, thereby offering a better prognosis. When specific treatment such as gene therapy becomes available, fetal diagnosis will identify the appropriate cases in utero. Although this approach is currently speculative, it is an area of great interest and endeavor. Thus, prenatal diagnosis of hemoglobinopathies has led to the development of fetal diagnosis of many genetic diseases, and resulted in techniques for obtaining fetal blood or DNA specimens. In addition to these scientific advances, it has also led to the control of thalassemia in certain geographic areas in which the public health burden involved in the management of such cases is overwhelming. Reduction of the number of newborn thalassemics is a necessity in some places, because appropriate care has not been possible, and the lifespan of affected individuals is significantly shortened or at least uncertain. All approaches to management of this disease are relevant, including improved treatment, specific therapy, and prenatal diagnosis. Each country and each family must determine for itself where to place the emphasis.
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PMID:Antenatal diagnosis of thalassemia: a review. 389 76

Recombinant DNA technology now provides the strategies required to identify genes whose expression controls the development of normal and pathologic blood cells. Characterization of the gene families responsible for synthesis of hemoglobins, immunoglobulins, histocompatibility antigens, and cellular enzymes have already, or are about to, provide major insights into the mechanisms producing normal erythroid cells, immunocytes, and immune surface features. Hemoglobinopathies, leukemias, and autoimmune diseases of the bone marrow can now be examined to a degree of detail previously inaccessible to investigators. Oncogene translocation analysis is shedding new light on the pathogenesis of leukemias and lymphomas. Recent basic advances now permit direct cloning and identification of genes in host organisms which express their protein products, thus allowing isolation of genes coding for the hematopoietic surface markers and growth factors which characterize and regulate blood cell progenitors. This review summarizes the molecular genetic approach to analysis of normal and pathologic hematopoiesis, surveys major findings which have resulted, and examines the potential use of refined gene cloning strategies for improved understanding of blood cell development.
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PMID:Analysis of gene expression during hematopoiesis: present and future applications. 390 64

Prenatal diagnosis of thalassemia and of the hemoglobinopathies is now accepted as an effective measure to reduce the impact of these diseases in populations where they occur in high frequencies. The procedure has been carried out on more than 5,000 cases over the past decade. Evaluation of the results shows a significant decrease of the yearly number of affected newborns and reflects a considerable gain in economic and medical resources. Methodology has improved over the years so as to make the procedure safer, faster, and less expensive. Among recent advances, gene mapping on trophoblast DNA (as early as the 9th week of pregnancy) represents a major step which will gradually replace conventional procedures (performed during the 18-20th week of pregnancy) in concerned laboratories.
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PMID:Prenatal diagnosis of thalassemia and of the hemoglobinopathies; a review. 391 Jun 16

Direct analysis of fetal DNA using restriction endonucleases constitutes a major area of progress in prenatal diagnosis. This recent technology may permit the precise identification of a mutant allele for some diseases, whereas in others it allows the familial segregation of a pathogenic allele to be followed by its linkage to a DNA sequence polymorphism. This type of analysis, available in a few centers, is currently used, among others, for the prenatal diagnosis of hemoglobinopathies such as sickle cell anemia. After fetal cells have been obtained by choriocentesis or amniocentesis, the extracted DNA is exposed to selected restriction enzymes. In the diagnosis of sickle cell anemia the mutant codon responsible for the substitution of glutamic acid by valine in the beta hemoglobin chain is no longer cut by the enzyme Mst II, due to its variance with the normal codon; this difference in fragment length is detected by DNA electrophoresis, and the particular fragments are identified by molecular hybridization with appropriate radioactive probes. Utilizing these methods the genotype of a homozygous normal fetus can be distinguished from that of a homozygote affected or a heterozygote for the sickle mutation of the beta hemoglobin chain. We have recently applied this prenatal methodology to the pregnancies of two couples from Zaire, in which each member was a proven sickle cell carrier. Fetal material was obtained in both cases by amniocentesis at the 16th week of gestation and followed by cell culture. In the first case, a 46, XX fetus, DNA (10 mcg) revealed a heterozygous sickle cell carrier genotype.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Prenatal prevention of drepanocytosis: analysis of cellular DNA in 2 cases]. 402 Mar 52

Hemoglobin and DNA gene analyses were carried out in two Black Canadian families. In Family Q, both the parents and the brother were found to be heterozygotes for alpha-thalassemia-2 with the following alpha-genotypes: -alpha 3.7/alpha alpha, -alpha 4.2/alpha alpha and -alpha 4.2/alpha alpha, respectively. In Family C, the mother was found to be a homozygote for alpha-thalassemia-2 with the alpha-genotype of -alpha 3.7/-alpha 3.7. In both families, the propositi were compound heterozygotes for alpha-thalassemia-2 with the alpha-genotype of -alpha 3.7/-alpha 4.2. The propositus in Family C was also a sickle cell trait carrier. The usefulness of DNA gene analyses in family studies of hemoglobinopathy was discussed.
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PMID:Compound heterozygosity for two genotypes of alpha-thalassemia-2: hematological, biosynthetic and DNA studies. 403 Mar 79

This article presents an overview of the use of fetal blood and DNA for prenatal testing. The molecular organization of the human hemoglobin genes, the structure of human hemoglobins, and the molecular defects of hemoglobinopathies are also discussed.
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PMID:The intrauterine diagnosis of hemoglobin disorders. 608 5

An extensive stem-loop structure was found in the A gamma-globin promoter region. Intron transcripts from epsilon-globin, A gamma-globin, delta-globin, and beta-globin were complementary to the loop sequence. A model for globin-switching based upon changes in DNA secondary structure and intron transcript pairing was proposed. Pairing of the epsilon intron transcript with the anti-sense strand was postulated to result in up-regulation whereas pairing of the sense strand with the intron transcripts from A gamma-globin, delta-globin, and beta-globin was postulated to result in down-regulation. The model is consistent with known hemoglobin disorders and can be extended to account for any series of genes that are turned on and off as development proceeds.
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PMID:Secondary structure and intron-promoter homology in globin-switching. 620 Oct 65

By using probes for epsilon-, Psibeta(1)-, and beta-globin genes, we found four additional polymorphic restriction sites that have frequencies >0.1 in persons of Mediterranean area origin, Asian Indians, and American Blacks. Three of these (HincII sites) and the two previously described polymorphic HindIII sites [one in intervening sequence (IVS) II of each gamma-globin gene] are distributed over 32 kilobases (kb) of DNA located 5' to the delta-globin gene. This region of DNA comprises two-thirds of the beta-globin gene cluster. Since each of these five polymorphic sites can be present (+) or absent (-), in theory there exist 32 possible combinations of sites (haplotypes). However, in Italians, Greeks, Indians, and Turks, 3 of the 32 haplotypes, (+----), (-+-++), and (-++-+), account for 92% of 89 beta(A) chromosomes examined. The observed frequencies for these haplotypes are 0.64, 0.15, and 0.13 in the populations studied, in contrast to expected frequencies (based on the observed gene frequencies at each of the five sites) of 0.20, 0.006, and 0.005, respectively. In American Blacks, a fourth haplotype, (----+), which is rare in non-Black populations, has a frequency of 0.37 in contrast to its expected frequency of 0.05. These results suggest a nonrandom association of DNA sequences over 32 kb 5' to the delta-globin gene in all populations studied. Two other polymorphic sites 3' to the delta gene (the newly discovered Ava II site in IVS II of the beta-globin gene and the BamHI site 3' to it) are nonrandomly associated with each other but randomly distributed with respect to the above haplotypes. This suggests that randomization of sequences has occurred within 12 kb of DNA between these two nonrandomly associated sequence clusters. Nonrandom association of polymorphic restriction sites has practical consequences in that it limits the usefulness of these additional HincII sites for prenatal diagnosis of hemoglobinopathies by linkage analysis. These sites provide little additional information for detection of beta-thalassemia, while the polymorphic Ava II site, which lies outside the nonrandomly associated sequences 5' to the delta gene, improves the test applicability from 52% to 70% of couples at risk.
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PMID:Nonrandom association of polymorphic restriction sites in the beta-globin gene cluster. 627 83


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