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

Concomitant inheritance of alpha-thalassemia in patients with beta 0-thalassemia/hemoglobin (Hb) E disease was detected by restriction endonuclease DNA mapping. Among 42 patients with beta 0-thalassemia/Hb E disease, seven were found to have an alpha-thalassemia-2 haplotype. Of these, five belonged to the rightward or 3.7-kb type of alpha-thalassemia-2 and the remaining two the leftward or 4.2-kb type. All the seven patients with alpha-thalassemia-2 haplotype had hemoglobin levels of 7.4 g/dl or above; those without detectable alpha-thalassemia had hemoglobin levels both higher and lower than 7.4 g/dl. The latter attended the clinic regularly, the former did occasionally. These findings suggest that concomitant inheritance of alpha-thalassemia can alleviate the severity of beta 0-thalassemia/Hb E disease. Failure to find alpha-thalassemia-1 haplotype in these patients suggests that concomitant inheritance of alpha-thalassemia-1 with beta 0-thalassemia/Hb E might lead to so mild a condition that the individuals do not present clinically. The fact that many patients without a detectable alpha-thalassemia haplotype also had hemoglobin levels of 7.4 g/dl or higher suggests that there are additional factors responsible for the mildness of beta 0-thalassemia/Hb E disease.
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PMID:Concomitant inheritance of alpha-thalassemia in beta 0- thalassemia/Hb E disease. 299 83

Restriction site polymorphisms are normal inherited variations in DNA that can be readily detected by restriction endonuclease analysis. Currently, 17 such polymorphisms are recognized within a 60 kb (kilobase) stretch of DNA which includes the beta-globin gene complex. Because of their proximity to the beta-globin gene, often these restriction site polymorphisms can be used to predict inheritance of beta-globin variants that produce disease. For example, restriction site polymorphisms can be used for prenatal diagnosis for the large majority of couples at risk of having a child with beta-thalassemia. When each member of such a couple is heterozygous at one or more of these 17 sites, family studies are usually successful in determining which forms of the polymorphism are co-inherited with the beta-thalassemia genes in that particular family. Subsequently, study of fetal DNA isolated from amniocytes obtained by midtrimester amniocentesis or from chorionic villi obtained by first trimester chorion biopsy will reveal which DNA polymorphisms that fetus has inherited. By deductive reasoning one can then predict which beta-globin genes it has co-inherited. Because of the general nature of these polymorphisms, which are related to the beta-globin gene and its variants only because of their proximity on chromosome 11, they are potentially useful in the prenatal diagnosis of any beta-chain hemoglobinopathy. Some hemoglobinopathies (including alpha-thalassemia, sickle cell anemia, and some cases of beta-thalassemia) can be detected directly by DNA analysis. In these cases in utero diagnosis does not need to rely on restriction site polymorphisms, which require preliminary family studies and are not applicable in all at risk pregnancies. Recently, genetic probes, which are necessary for detecting restriction site polymorphisms, have been isolated for sequences of several genes whose protein products are important in blood coagulation. These include probes for all three genes whose polypeptide products combine to form the fibrinogen molecule as well as probes for the prothrombin, Factor IX, Factor VIII, and antithrombin III genes. Defects in these genes are expected to be the causes of afibrinogenemia, prothrombin deficiency, hemophilia B, hemophilia A, and antithrombin III deficiency, respectively. From experience with other genes, it is expected that restriction site polymorphisms within and/or flanking these genes will be found.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prenatal diagnosis of hemoglobinopathies by DNA analysis. 299 37

We carried out alpha-globin gene analysis by restriction endonuclease mapping in a family with 2 cases of HbH disease. These data show that HbH disease in this family results from the interaction between a common deletional defect and a less common non-deletion alpha-thal lesion (--Med/alpha alpha thal). Furthermore, the presence of a beta-thal determinant in this family was investigated by beta gene polymorphism study. We showed that a patient with HbH disease also inherited a beta-thal determinant from the mother and although this was a beta O-thal gene, it was not sufficient to mask the severe alpha chain deficiency. The --Med/alpha alpha thal genotype is more severe than other types of alpha thalassaemia interactions causing HbH disease, probably because the expression of alpha alpha thal determinant may be lower than that of an alpha-thal determinant containing just a single alpha gene (-alpha) and the output so poor that the presence of one beta-thal gene does not significantly change the clinical picture.
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PMID:Clinical severity of non-deletion form of HbH disease (--Med/alpha alpha thal). 300 23

In this study we have characterised by oligonucleotide hybridisation and direct restriction endonuclease analysis the beta thalassaemia mutation in 494 Sardinian beta thalassaemia heterozygotes. The most prevalent mutation, accounting for 95.4% of the cases, was the nonsense mutation at codon 39. The remainder, in decreasing order of frequency, were a frameshift at codon 6 (2.2%), beta + IVS-1, nt 110 (0.4%), and beta + IVS-2, nt 745 (0.4%). This information allows prenatal diagnosis by DNA analysis to be made in the great majority of Sardinian couples at risk for beta thalassaemia.
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PMID:Beta thalassaemia mutations in Sardinians: implications for prenatal diagnosis. 303 Dec 99

This paper describes the case of a 6-year-old Saudi male who had sickle cell heterozygosity, beta +-thalassaemia and possessed three alpha-genes of the haplotype alpha alpha alpha anti-3.7/as diagnosed by restriction endonuclease studies using Hpa I, Bam HI, Bgl II, Hind III and Xba I. Since the iron level was found to be normal, it is proposed that the coexistence of beta-thalassaemia with triple alpha-genes in Hb S heterozygotes may be the cause of the anemia. A possible mechanism for severe anaemia is presented.
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PMID:Triple alpha genes in association with sickle cell and beta-thalassaemia gene in the Saudi population. 303 78

A relationship between Hb Bart's levels in cord blood and the number of alpha-globin genes has been established by screening cord blood samples from 1,075 newborn babies. Diagnosis was made by gene mapping of DNA samples with restriction endonuclease digestion. The presence of Hb Bart's was determined with a discontinuous microelectrophoresis on cellulose acetate at pH 8.34. The establishment of this relationship allows an early diagnosis of alpha-thalassemia by this simple microelectrophoretic procedure.
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PMID:The relationship between Hb Bart's levels in cord blood and the deletions of alpha-globin genes. 320 94

We have used four oligonucleotide probes and two restriction enzymes to detect the beta thalassaemia mutation in a group of 61 couples of Italian descent who were prospective parents. We have been able to define the beta thalassaemia mutation in both parents in 47 couples and in only one parent in 12 couples. Prenatal diagnosis was accomplished successfully either by amniocyte (two) or trophoblast (26) DNA analysis in 28 couples in which the pregnancy was in progress. These results indicate that direct identification of the mutation by oligonucleotide or restriction endonuclease analysis is a practical and useful method for prenatal diagnosis of beta thalassaemia in childless couples.
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PMID:Prenatal diagnosis of beta thalassaemia by oligonucleotide analysis in Mediterranean populations. 323 55

Using oligonucleotide hybridisation or restriction endonuclease analysis, we have characterised the molecular defect in 94 patients with thalassaemia major and four with thalassaemia intermedia of Turkish Cypriot descent. We found that four mutations, namely beta+ IVS-1 nt 110, beta zero IVS-1 nt, beta+ IVS-1 nt 6, and beta+ IVS-2 nt 745 were prevalent, accounting for 69.9%, 11.7%, 8.7%, and 5.6% respectively of the beta thalassaemia chromosomes. This information may help in the organisation of a large scale prevention programme based on fetal diagnosis of beta thalassaemia by DNA analysis in the Turkish population.
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PMID:Beta thalassaemia mutations in Turkish Cypriots. 323 56

In this study, we defined by haplotype characterization combined with oligonucleotide hybridization or direct restriction endonuclease analysis the specific beta-thalassemia mutations in a representative sample of beta-thalassemia chromosomes from patients with homozygous beta-thalassemia originating from different parts of Italy. We characterized the mutations in 90% of the thalassemia chromosomes and found that three mutations, namely the beta(+)IVS 1-110, beta (0)-39 and beta(+)IVS 1-6 are prevalent in the Italian population. Most of the patients investigated were compound heterozygotes for two beta-thalassemia mutations, and only a few were homozygotes for one mutant. On the basis of these findings, we predict that prenatal diagnosis in this population would be feasible in most cases by fetal DNA analysis with the oligonucleotide method using a limited number of oligonucleotide probes selected after screening parents for the most common beta-thalassemia mutations. We have also devised a method based on hybridization with a mixture of two oligonucleotides that allows rapid and simultaneous screening of prospective parents for the two most frequent mutations in Italians, the beta(+)IVS 1-110 and beta(0)-39 mutants. This method may be applicable to prenatal diagnosis in cases at risk for the genetic compound of these mutations.
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PMID:Delineation of specific beta-thalassemia mutations in high-risk areas of Italy: a prerequisite for prenatal diagnosis. 335 99

We have determined the spectrum of mutations producing beta-thalassemia (beta-thal) in Tunisia by direct DNA analysis using hybridization with allele-specific oligonucleotide probes and restriction endonuclease assay. In all, 34 unrelated beta-thal patients originating from different parts of the country were available for study. The beta-globin gene cluster of each was subjected to haplotype analysis, and on the basis of this analysis, we tested each patient's DNA for one or more mutations previously shown to be linked to that haplotype. We identified four previously unreported haplotypes and found that this population differs from others in Mediterranean areas in the frequency of the beta-thal haplotypes, the unexpected observation being the high frequency of haplotype IX. Six different point mutations were found, accounting for 62% of beta-thal genes in this Tunisian population. The molecular defects known to be the most frequent in Mediterraneans (nonsense codon 39, IVS1 nt 110, IVS1 nt 6) only make up 37% of the mutant genes. One as yet undescribed mutation (IVS1 nt 2 T----G) was identified by molecular cloning and sequencing. Our results should help the implementation of a prenatal diagnosis program for beta-thal in Tunisia.
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PMID:The peculiar spectrum of beta-thalassemia genes in Tunisia. 342 18


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