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

We have summarized a number of different genetic disorders which can be diagnosed at the DNA level using restriction endonuclease fragment analysis. A whole spectrum of defects can be recognized: point mutations, deletions, additions, and crossing-over products or hybrid genes. These same restriction endonuclease techniques can enable different genes to be marked by polymorphism patterns. Thus, abnormal genes can be identified even if their exact DNA lesion is unknown or cannot be directly detected. The progress that has been made with the hemoglobinopathies and the experience from this group of single gene disorders should find application to other diseases as soon as specific probes become available.
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PMID:Genetic diseases: diagnosis by restriction endonuclease analysis. 628 49

DNA polymorphisms are normal inherited variations in DNA that can often be used to document the inheritance of genes that produce disease. In this report we summarize our experience with prenatal diagnosis in 95 pregnancies in which the fetus was at risk for a hemoglobinopathy; the diagnosis was performed with use of DNA polymorphisms located so near the beta-globin gene that they are inherited along with that gene. Of the 95 pregnancies, 57 involved fetuses at risk for sickle-cell anemia, 32 fetuses at risk for beta-thalassemia, and 6 fetuses at risk for other beta-chain hemoglobinopathies. Diagnosis was achieved solely by analysis of DNA polymorphisms in cells recovered by amniocentesis in 82 cases (86 per cent) and was completed by fetoscopy and fetal-blood study in an additional 6 cases (6 per cent). Prenatal diagnosis was proved correct in all 78 cases that have been available for confirmation to date. Our experience demonstrates that DNA polymorphisms can be useful for the prenatal diagnosis of genetic diseases in which the basic defect cannot be directly detected.
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PMID:Prenatal diagnosis using DNA polymorphisms. Report on 95 pregnancies at risk for sickle-cell disease or beta-thalassemia. 630 Jun 77

These are exciting times in human genetics. Recombinant DNA technology has enabled investigators to sequence human genes so that the structure and organization of some genes is now known. These observations led to studies of "natural mutations," such as the hemoglobinopathies and thalassemias. This information in turn provided insight so that many mutations affecting the alpha- or beta-globin genes can now be detected prenatally. It seems probable that these techniques will be applicable to many other human genetic diseases. In the future, however, the greatest impact of these advances may be through their applications to produce proteins, such as hormones and vaccines, which can be used to treat deficient patients.
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PMID:Clinical applications of restriction endonuclease analysis. 630 71

Prevention of thalassemia and hemoglobinopathies is the only solution to efficiently reduce the huge medical, social and economic impact of these diseases in countries where they occur in high frequencies. In Greece, a serious effort has been undertaken towards this goal over the last years. Prevention is carried out at various levels: ample public education, easy provision of the necessary laboratory tests for carrier identification and thorough counseling of the couples at risk. Availability of prenatal diagnosis has contributed significantly to the acceptance by the public of various screening programmes. To date, the experience of the Greek group for prenatal diagnosis totals 1088 cases (June 1977 to December 1982). The number of couples at risk seeking the test prior to having any children is steadily increasing (prospective counseling). The efficacy of the overall prevention programme in Greece is reflected by the fact that the number of babies with thalassemia major admitted for transfusion to the major Units of the country has decreased substantially in the last years. Routine method used for prenatal diagnosis is biosynthesis of hemoglobin in samples of placental blood drawn by fetoscopy. With increasing experience the procedure now is safe (less than 1% of obstetrical complications in the last year) and the prediction accurate (no false diagnoses in the recent years). However, it is anticipated that the conventional method will soon be replaced by studies of amniotic cell DNA, a procedure both safer and less traumatic, or by studies of trophoblast DNA, which will allow prenatal diagnosis at an earlier stage of pregnancy.
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PMID:Prevention of thalassemia. 631 86

Prenatal testing for hemoglobinopathies has been available since 1974, using fetal blood samples, and since 1978, using fetal DNA. Close to 2000 cases were studied by analysis of fetal globin synthesis, and approximately 100 by restriction enzyme techniques. More than 20 centers worldwide are performing these tests. The safety and reliability of these tests are now clear, and they have a major role in the counselling of families where there is a risk of sickle cell disease or thalassemia.
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PMID:Prenatal diagnosis of hemoglobinopathies: development of methods for study of fetal red cells and fibroblasts. 632 8

Recombinant DNA technology has made possible remarkable advances in understanding the molecular genetics of human and other eucaryotic cells. This technology also has clinical applications, some of which may soon involve clinical laboratories. Restriction endonucleases and cloned DNA probes permit the direct analysis of cellular DNA to detect sequence abnormalities associated with particular genetic disorders. Use of this approach in the antenatal diagnosis of hemoglobinopathies is now possible on a routine basis. The principles behind the methods are quite general and may be applied to other hereditary diseases once suitable DNA probes become available. The same approach may be used to detect carriers of recessive gene defects and so improve genetic counselling. Other clinically related applications of recombinant DNA technology include the production of antigens for vaccine preparation and of specific human proteins (e.g. interferon and human growth hormone) for therapeutic use, as well as the use of nucleic acid hybridization for identification of microbial pathogens. It seems likely that recombinant DNA technology will, in the future, play an increasingly important role in the diagnosis, prevention and treatment of human disease.
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PMID:Some clinical implications of recombinant DNA technology with emphasis on prenatal diagnosis of hemoglobinopathies. 632 48

One of the most significant advances in medicine is the development of prenatal diagnosis. In many circumstances it is now possible for the physician to learn definitively whether or not a fetus has a given genetic disorder. If the fetus is found to be affected, the couple may elect termination of the pregnancy. The most widely used technique for prenatal diagnosis is midtrimester amniocentesis, which permits chromosomal or enzymatic studies of amniotic liquor and cultured amniotic fluid cells. Recent advances in DNA analysis of amniotic fluid cells have opened new vistas for the antenatal detection of hemoglobinopathies, and potentially, for other genetic disorders. Advances in ultrasonography have not only made amniocentesis safe and more reliable, but have also offered new opportunities for the detection of certain defects. Finally, in addition to allowing direct fetal visualization, fetoscopy has permitted access to fetal tissues (e.g., blood, skin), thereby making feasible the diagnosis of disorders not otherwise detectable.
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PMID:Prenatal diagnosis of genetic disorders. 634 64

Prenatal diagnosis of hematologic diseases can now be performed with fetal blood, fetal amniotic fluid cell DNA, and fetal chorionic villi DNA. Some hemoglobinopathies can be detected by all three methods, and the choice will depend on the available obstetric and laboratory techniques, as well as the time of presentation of the pregnancy. Hopefully, further development of molecular probes and techniques will soon expand these options to all of the globin disorders. Detection of coagulation disorders in utero currently requires samples of pure fetal blood. Gene cloning is accomplished for some (factor IX and antithrombin III) and is underway for others (factor VIII), and further investigation is necessary to determine whether deficiencies in these gene products are due to gene deletion or to mutant genes linked to polymorphic restriction enzyme sites of diagnostic use. Thus, molecular biology may be applied to prenatal diagnosis of the clotting problems, but this has not yet been accomplished. Disorders affecting the number and/or function of erythrocytes, leukocytes, and platelets can be diagnosed by analysis of fetal blood. Blood samples will continue to be required until more is known about the molecular biology of hematopoiesis. Syndromes that can be diagnosed by chromosome studies should be revealed in cultures of amniotic fluid cells, fetal blood lymphocytes, and chorionic villi cells. Cultured cells can be examined for karyotypes, Y-chromatin, spontaneous or induced chromosome breakage, DNA repair, SCEs, and translocations. The techniques for culturing amniotic cells and fetal blood white cells are established, and those for growing cells from chorionic villi are improving rapidly. Direct preparations of cells from villi only may suffice for some of the above analyses. The study of hematologic disease in utero has thus come full circle, from the use of amniotic cells to determine the sex in X-linked disorders, to fetal blood sampling for the analysis of gene products, then back to amniocentesis for DNA, and now earlier in gestation to chorionic villi. All of this has occurred in less than ten years, and it is anticipated that developments in the next ten years will be equally dramatic. The future should bring all prenatal testing into the first trimester, use molecular probes, and provide for both early diagnosis and early treatment of genetic hematologic disease.
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PMID:Advances in the prenatal diagnosis of hematologic diseases. 637 72

We describe a rapid procedure for constructing cloned human genomic libraries from small amounts of peripheral blood. High molecular weight DNA is isolated from 5-20 ml peripheral blood, partially cleaved with Eco R1, and 8-22 kb fragments are cloned using bacteriophage Charon 4A and suitable E. coli host. Using the approach we have isolated and characterized several non-alpha globin clones from a Kurdish Jew with homozygous beta thalassemia. The ability to isolate suitable amounts of high molecular weight DNA from peripheral blood provides a relatively simple means of constructing human gene libraries representing a variety of hemoglobin disorders.
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PMID:Construction of human gene libraries from small amounts of peripheral blood: analysis of beta-like globin genes. 706 33

Amniocentesis and fetoscopy are two of several modalities used to offer information during the prenatal period of the status of the fetus. Amniocentesis is most frequently used and with continuing research is becoming an invaluable aid to prenatal diagnosis. With the recent studies of DNA characteristics of globin chains of cells obtained at amniocentesis, the need to obtain blood directly from fetal vessels to diagnose major hemoglobinopathies prenatally is rapidly diminishing. Open neural tube defects are diagnosable with alpha feto protein analysis. All chromosomal defects are accurately quantitated and more than 100 inborn errors of metabolism are predictable. Fetoscopy is a technique which has a limited utility. It should be confined to major centers where adequate midtrimester abortions are done in order to provide training for those who aspire to pursue this method. With fetal blood sampling the following conditions are detected: beta thalassemia major, Hemophilia A, sickle cell anemia, chronic granulomatous disease, galactosemia and Tay Sachs disease, all of which may be diagnosed directly. Alpha and beta thalassemia, Hemophilia B and homozygous Von Willenbrand's disease may be excluded. With fetal biopsy one can diagnose congenital bullous ichthyosiform erythroderma ichthyosis. During the last ten years the amount of information brought to our attention has also brought the expectation that the next decade will be the most fruitful period in our history in this discipline.
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PMID:Amniocentesis and fetoscopy. 714 20


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