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)

We used the chemical cleavage of mismatch (CCM) method to screen the beta-globin gene simultaneously for Mediterranean beta-thalassemia mutations. The beta-globin gene was amplified in two segments encompassing the whole gene and hybridized to a corresponding labeled PCR product from a normal subject. All the known mutations tested were identified and discriminated. Three beta-thalassemic subjects with previously undiagnosed mutations were identified as carriers of two rare DNA changes. The inheritance of the mutations could be traced in family studies, showing the reliability of the method even for prenatal diagnosis. The beta-globin gene polymorphisms were also detected and the framework was determined for most alleles. Our results suggest further applicability of the CCM method as a means to screen a gene simultaneously for multiple mutations.
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PMID:Simultaneous screening for beta-thalassemia mutations by chemical cleavage of mismatch. 176 85

Five beta-thalassaemia mutations hitherto undescribed in Asian Indians were identified in beta-thalassaemia carriers originating from the Indian subcontinent by direct sequencing of their beta-globin genes which were amplified by the polymerase chain reaction (PCR). A T-G substitution at IVS 2 position 837, which probably creates an alternative acceptor splice site and a T insertion in codon 88, resulting in a shift in the reading frame with a premature stop codon, are new beta-thalassaemia mutations. The others were framshift codon 5 (-CT), IVS 1 position 110 (G-A) and IVS-1 minus 1 (G-A) which have been described previously in other populations. These results complete the characterization of the beta-thalassaemia mutations in 708 carriers of Asian Indian origin and will enable a comprehensive programme of carrier screening and prenatal diagnosis of beta-thalassaemia in this population.
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PMID:Rare beta-thalassaemia mutations in Asian indians. 177 86

We describe the hematological and clinical data for a young Greek patient with beta-thalassemia intermedia and for several members of her family. The patient had inherited the common IVS-I-1 (G----A) mutation from her mother, while the second beta-globin gene had a C----G mutation at position 6 3' to the terminating codon (term. + 6). Her father and three additional relatives with a heterozygosity for this newly discovered mutation had no hematological abnormalities, normal Hb A2 values, and a nearly normal in vitro chain synthesis ratio. Analyses of nearly 500 additional beta-thalassemia and normal chromosomes failed to detect this mutation which eliminates it as a common polymorphism. Although our findings may indicate a rare polymorphism, the probability that it represents the cause of diminished beta chain synthesis is very high indeed. We suggest that the C----G mutation in this untranslated region of the beta-globin gene causes a slight decrease in the stability of the mRNA which becomes clinically important only in situations when beta chain synthesis in trans is eliminated.
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PMID:A C----G mutation at nt position 6 3' to the terminating codon may be the cause of a silent beta-thalassemia. 177 3

We report a Swiss-Spanish family three members of which have the clinical picture of thalassemia intermedia. Restriction endonuclease mapping of the alpha-globin cluster and digestion with Mae I of the in vitro amplified 5' segment of the beta-globin gene shows a combination of triplicated alpha globin locus, anti-3.7 kb type, with heterozygous codon 39 C----T beta (0) thalassemic mutation. These, as well as 16 similar cases reported in the literature, permit the following conclusion: a single extra alpha-globin gene gives rise to a clinically significant degree of dyserythropoietic anemia only when it interacts with a severe beta(+) or beta(0) thalassemic mutation.
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PMID:Interaction of heterozygous beta (0)-thalassemia and triplicated alpha globin loci in a Swiss-Spanish family. 179 94

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

In this review I have discussed the state of our knowledge of the molecular basis of beta-thalassemia and its prenatal diagnosis. Improved but more complicated genetic counselling is now available as a result of our increased knowledge of the effects of various defects in the beta-globin gene. Our knowledge of the heterogenous molecular basis of the thalassemia syndromes has become very impressive and it is hoped that effective therapy will soon follow. However, for the present, prevention of the birth of affected children is the most effective means of reducing the suffering associated with the thalassemia syndromes, and prevention of this type is succeeding in many parts of the world, including North America.
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PMID:Prenatal diagnosis of beta-thalassemia. 188 58

Molecular analysis of gene structure using PCR related techniques has been described. These techniques were applied to analysis of the beta-globin gene from Japanese individuals with beta-thalassemia. We found one promoter mutation, two splicing mutations, two frameshift mutations, one nonsense mutation. We also detected three different mutations within the third exon. They produced highly unstable globin variants, leading a dominantly inherited beta-thalassemia phenotype. Six of nine different mutations seem to originate in Japanese. Characteristics of molecular defects of Japanese beta-thalassemia was discussed in terms of malaria hypothesis.
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PMID:[Molecular analysis of thalassemia]. 189 Jul 33

An extension of previous reports describing the molecular defects and hematological abnormalities in black patients with Hb S(C) beta-thalassemia living in the Southeastern United States is presented. As many as 58 patients with Hb S-beta(+)-thalassemia, 16 with Hb C-beta(+)-thalassemia and 12 with Hb S-beta(0) -thalassemia have been studied. Patients with Hb S(C) beta(+)-thalassemia type 2 (high Hb A values) were most common; the thalassemia was due to mutations in the promoter of the beta-globin gene [-88 (C----T) and -29 (A----G)] or at the polyadenylation signal (T----C). Two patients with lower Hb A values (type 1) carried a mutation in the first intron of the beta-globin gene (IVS-1-5: G----T). The simultaneous presence of an alpha-thalassemia -2(-alpha/) resulted in some modifications of the hematological parameters, but had a minimal effect on the clinical condition. Patients with Hb S-beta (0) thalassemia had lower hemoglobin values, lower number of red blood cells, and lower MCHC values and suffered more frequently from complications than the patients with Hb S-beta(+)-thalassemia. A total of 17 different beta-thalassemia mutations were observed in 128 chromosomes; two mild beta(+)-thalassemia mutations [-88(C----T) and -29(A----G)] account for more than 80% of the thalassemic chromosomes.
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PMID:Molecular characterization of Hb S(C) beta-thalassemia in American blacks. 189 18

A previously undescribed mutation (-1, +3, codon 24) causing beta-thalassaemia was identified in an Egyptian patient. It consists in the concomitant deletion of a G in codon 24 and its replacement with the new trinucleotide CAC, thus resulting in the shift of the beta-globin reading frame. The sequence of the chromosome of interest was isolated from the homologous one by means of selective hybridization to an immobilized oligonucleotide. The presence of this mutation in the proband's family was confirmed by dot blot hybridization with an oligonucleotide probe.
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PMID:A new beta-thalassaemia frameshift mutation detected by PCR after selective hybridization to immobilized oligonucleotides. 191 91


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