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)

Using the polymerase chain reaction (PCR), it was possible to amplify a single copy fragment of the beta-globin gene from 2-32 human embryonic cells obtained from arrested preimplantation embryos. For the detection of beta-thalassaemia mutations, allele specific priming of the PCR using nested primers was employed using approximately 10 pg of DNA from individuals known to carry these mutations. This approach was successful in detecting the presence or absence of five Asian Indian beta-thalassaemia mutations that were selected for this study. In spite of meticulous precautions against contamination, false-positive amplification was observed, a problem that will have to be overcome before this approach can be used in clinical practice.
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PMID:An approach to preimplantation diagnosis of beta-thalassaemia. 180 Sep 89

A simple procedure for nonradioactive labeling of oligonucleotides has recently been developed (1). It consists of 3' end labeling of oligonucleotides with terminal transferase by incorporation of a single digoxigenin labeled dideoxy uridine triphosphate. We used these oligonucleotides for allele specific oligomer hybridization of polymerase chain reaction amplified DNA, followed by an enzyme-linked immunoassay and subsequent enzyme-catalyzed color reaction. We compared this procedure with the standard radioactive oligonucleotide hybridization technique through the detection of the most common Mediterranean beta-thalassemia mutations. This procedure was also used for the confirmation of a new mutation at position -87 (C----A) (2) of the beta-globin gene and for the subsequent family analysis.
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PMID:Detection of beta-thalassemia mutations by ASO hybridization of PCR amplified DNA with digoxigenin ddUTP labeled oligonucleotides. 181 58

1. The molecular abnormality of a patient with thalassemia intermedia was identified by DNA amplification (PCR) combined with the use of synthetic oligonucleotide probes. 2. The patient is a homozygote for the T----C substitution at position 6 of the first intervening sequence (IVS1-6) of the beta globin gene. 3. On the basis of this finding, the family, which had been previously reported by us to be a carrier of an unusually mild beta-thalassemia gene, was actually the first example reported of the clinical and biochemical features of beta-thalassemia-Portuguese type.
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PMID:Beta-thalassemia intermedia and IVS-1 NT6 homozygosis in Brazil. 182 28

Mass screening of married couples in the town of Baku has revealed a couple at risk of giving birth to a child with homozygotic beta-thalassemia. Prenatal diagnosis was carried out during week 23 of pregnancy by means of cordocentesis and biochemical analysis of globin chains, in vitro synthesized in fetal blood in the presence of labeled leucin. beta-thalassemia was detected in the fetus, similarly as in the child in this family. Abortion was induced on pregnancy week 25. Prenatal diagnosis is recommended in case of another pregnancy during the first trimester, involving analysis of the chorionic villi DNA.
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PMID:[Prenatal diagnosis of beta-thalassemia]. 183 13

A mild, non-transfusion dependent, beta thalassaemia phenotype is described in a Dutch patient homozygous for a mutation in the cleavage-polyadenylation sequence of the beta globin gene. The molecular basis of the mutation, AATAAA greater than AATGAA, was determined using denaturing gradient gel electrophoresis (DGGE) and direct sequencing of genomic DNA amplified by the polymerase chain reaction (PCR). Different fragments of the beta globin gene were amplified and analysed on DGGE for the presence of mutations. The fragment with an abnormal melting behaviour was reamplified and the base substitution in the polyadenylation sequence was identified by direct sequencing.
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PMID:Homozygous beta+ thalassaemia owing to a mutation in the cleavage-polyadenylation sequence of the human beta globin gene. 185 30

alpha-Thalassemia hydrops fetalis is a common disorder in Taiwan. The condition causes perinatal death and many maternal obstetrical complications. In order to determine the molecular defects of this condition in Chinese, 87 unrelated families with this disorder were collected in the past 4 years. The molecular defects were studied by Southern blotting and DNA hybridization with phi zeta 1-globin gene and LO (a 0.4 kb BamHI/EcoRI fragment in the 5' flanking region of the zeta 2-globin gene) probes. Eighty-one (93.1%) fetuses had homozygous Southeast Asian deletion (- -SEA/- -SEA). Five (5.7%) fetuses were compound heterozygotes for the Southeast Asian deletion and Thailand deletion (- -SEA/- -THAI). The remaining fetus was a compound heterozygote for the Southeast Asian deletion and an uncharacterized nondeletional defect (- -SEA/(alpha alpha)Th). The molecular defects of alpha-thalassemia hydrops fetalis in Chinese are heterogeneous. This fact has important implications for genetic counseling and prenatal diagnosis.
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PMID:Molecular characterization of severe alpha-thalassemias causing hydrops fetalis in Taiwan. 186 84

We have defined the molecular basis of normal HbA2 beta-thalassaemia associated with Hb Knossos. DNA sequence analysis of the delta globin gene in cis with beta Knossos showed deletion of a single A in codon 59 leading to a premature termination at codon 60. This delta 0/beta Knossos allele has been observed in three unrelated Egyptian families and associated with a single beta haplotype (+----++). One individual who was homozygous for the delta 0/beta Knossos allele as well as heterozygous for a non-deletional alpha thalassaemia, was completely clinically asymptomatic, while others have coinherited the delta 0/beta Knossos allele with different beta and alpha thalassaemia determinants. A study of the different genetic interactions giving rise to a spectrum of clinical phenotypes is reported.
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PMID:A novel delta 0 mutation in cis with Hb Knossos: a study of different genetic interactions in three Egyptian families. 187 27

Homozygous alpha zero-thalassaemia results in the fatal disease Bart's hydrops foetalis and since 3-4% of Singaporeans carry the alpha-thalassaemia genes, prenatal diagnosis of thalassaemia is essential. The aim of this study was to establish the polymerase chain reaction (PCR), a method that enables selective amplification of the 136 base pair (bp) region within the alpha-globin gene cluster, as a routine test for the prenatal diagnosis of homozygous alpha zero-thalassaemia. Confirmation of PCR results was performed using DNA gene mapping and electrophoresis of cord blood. DNA was extracted from 24 chorionic villi samples and the presence of the alpha-globin genes was determined by PCR. The results showed that the optimal number of amplifications for accurate diagnosis was 50 cycles. Homozygous alpha zero-thalassaemia was detected in four foetuses and the pregnancies terminated. Confirmation of alpha zero-thalassaemia by DNA gene mapping and electrophoresis of cord blood showed absence of alpha-globin genes and only Hb Bart's respectively. The remaining 20 foetuses were correctly diagnosed as normal or possessing the alpha-thalassaemia trait. Using the PCR at less than 50 cycles of amplification (example 35 cycles), false positive results were obtained in 30% of cases. We conclude that DNA amplification using the PCR offers an accurate method of prenatal diagnosis of alpha zero-thalassaemia. Its advantages over the more establish gene mapping method include a more rapid analysis (three days compared with ten days by gene mapping) and the requirement of only minute amounts of DNA (1 microgram) for analysis. It is however, essential that the optimal number of amplification cycles be established so that false positive results may be avoided.
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PMID:An evaluation of the polymerase chain reaction for detection of alpha-globin genes in the prenatal diagnosis of alpha zero-thalassaemia. 188 86

Identification of the beta s-gene-cluster haplotype and alpha-gene status provide a useful tool to improve the possibility for early detection in high-risk SS patients. The DNA polymorphisms of the beta s-gene-cluster modify the clinical course in sickle cell anemia especially as it involves the risk of end-stage organ failure of the kidney, lung, and brain. In both Africa and America, the CAR beta s haplotype increases the risk of developing irreversible complications at an early age. The degree of anemia, the Hb F concentration, and the preservation (or lack thereof) of G gamma Hb F is haplotype dependent and correlates with the overall clinical course of the patient. Further modulation of the clinical course by the coinheritance of alpha-thalassemia-2 tends to decrease the risk of soft tissue organ failure but increases the risk of osteonecrosis. A single individual can be expected to fit into the overall pattern. Some sickle related illness will eventually occur in all patients. In the presence of a Senegal haplotype, the patient's health is better, with the CAR haplotype it is always worse; severity is intermediate in the Benin. These genetic markers can be used to identify the endangered patient before the onset of irreversible major organ failure. The high risk SS patient with a CAR chromosome or one who is homozygous Ben without alpha-thalassemia-2 should be monitored closely for evidence of vasculopathy-induced microinfarction of the brain, kidneys, or lungs. Such a patient needs preventive therapy before suffering a major hemisphere stroke, losing kidney function, or developing cor pulmonale secondary to restrictive lung disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sickle cell anemia: beta s-gene-cluster haplotypes as prognostic indicators of vital organ failure. 188 45

The low concentration of the hemoglobin variant, Hb Vicksburg (leucine-beta-75 deleted), and a profound deficit of its mRNA led us to postulate that a beta(+)-thalassemia mutation existed in cis to the coding region mutation, suppressing its synthesis. We examined blood from this patient 6, 8, and 10 yr after our initial studies, using methods of analysis unavailable initially. We found 1) mutations causing beta(+)-(-88 C----T) and beta 0-(849 A----G) thalassemia; 2) that the proportion of Hb Vicksburg in erythrocytes fell over time, from 8 to 4%, and ultimately disappeared; and 3) that the mutation causing Hb Vicksburg was not detectable in genomic DNA isolated from blood leukocytes when this variant was present in hemolysate. We postulate that Hb Vicksburg arose from a somatic mutation of a beta(+)-thalassemia gene in an erythroid-committed stem cell. Its gradual disappearance suggests the cycling of stem cells, with inactivation of different clones over time.
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PMID:Disappearance of the protein of a somatic mutation: a possible example of stem cell inactivation. 188 72


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