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

We have developed a technique to diagnose the alpha- and beta-thalassemia (thal) syndromes using the polymerase chain reaction to amplify cDNA copies of circulating erythroid cell messenger RNA (mRNA) so as to quantitate the relative amounts of alpha-, beta-, and gamma-globin mRNA contained therein. Quantitation, performed by scintillation counting of 32P-dCTP incorporated into specific globin cDNA bands, showed ratios of alpha/beta-globin mRNA greater than 10-fold and greater than fivefold increased in patients with beta 0- and beta (+)-thal, respectively, as well as a relative increase in gamma-globin mRNA levels. Conversely, patients with alpha-thalassemia showed a decreased ratio of alpha/beta-globin mRNA proportional to the number of alpha-globin genes deleted. This methodology of ascertaining ratios of globin mRNA species provides a new, simplified approach toward the diagnosis of thalassemia syndromes, and may be of value in other studies of globin gene expression at the transcription level.
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PMID:Diagnosis of thalassemia using cDNA amplification of circulating erythroid cell mRNA with the polymerase chain reaction. 162 91

The 1.8-kb beta-globin gene fragments of DNAs from individuals heterozygous for nine different beta-thalassemia mutations involving 1, 2, 3, 4, or 25 basepair (bp) insertions or deletions were amplified by the polymerase chain reaction (PCR). The PCR products were subjected to electrophoresis on aqueous 8% polyacrylamide gel. In each heterozygote with either a 2 to 25 bp deletion, but not with a 1 bp insertion, two slower migrating bands representing heteroduplexes in addition to the 1.8-kb homoduplex band were seen. The electrophoretic positions of these slower migrating bands were characteristic of each mutation studied. By co-amplification with known normal DNA, it was also possible to distinguish DNAs from normal individuals and from individuals who are homozygous for the small insertion/deletion mutations. These studies demonstrate that the heteroduplex formation generated in PCR can be applied as a simple method in the diagnosis of insertion/deletion mutations involving 2 to 25 bp in beta-thalassemias as well as in other genetic disorders.
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PMID:A rapid and simple electrophoretic method for the detection of mutations involving small insertion or deletion: application to beta-thalassemia. 193 77

Clinically, homozygous beta-thalassaemia is characterised by a severe anaemia requiring regular transfusion therapy in most patients. However, there is a marked clinical variability ranging from this severe picture to the virtual absence of symptoms and haematological abnormalities. Biochemically, beta-globin synthesis in the erythroid precursors of the bone marrow is reduced or absent resulting in a relative excess of insoluble alpha-globin chains and dyserythropoiesis. The molecular genetics of this disorder is highly variable involving a multitude of different mutations of the beta-globin gene. These mutations can inactivate gene expression at all levels on its way from DNA to mature haemoglobin. The clinical picture is largely determined by the type of mutations inherited. Additionally the degree of alpha-globin chain excess can be influenced by the co-inheritance of alpha-thalassaemia or mutations resulting in the hereditary persistence of fetal globin synthesis (HPFH). This review discusses the relationship between the molecular defect and the clinical picture of patients with beta-thalassaemia.
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PMID:[Beta thalassemia: molecular pathogenesis and clinical variability]. 194 34

The beta-globin genes from a Thai patient compound heterozygous for beta(+)- and beta zero-thalassemias were investigated. Amplification and DNA analysis of genomic DNA by the polymerase chain reaction procedure permitted the identification of the beta-Malay mutation (beta 19;AAC-AGC) in one allele and a novel beta zero-thalassemia mutation (41;TTC-TT) in another allele.
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PMID:Double heterozygosity of the beta-Malay and a novel beta-thalassemia gene in a Thai patient. 195 6

A novel beta-chain, beta 126(H4)Val----Gly, electrophoretically silent, was detected by reverse-phase high performance liquid chromatography in three unrelated families from Naples (Southern Italy) and accounted for about 30% of the total beta-chains. The amino acid substitution was detected by HPLC fingerprint. The eight heterozygous patients showed hematologic and biosynthetic alterations of mild beta-thalassemia type. The hemoglobin variant showed abnormal stability features. It was unstable in the heat stability and isopropanol precipitation tests, but did not cause a hemolytic syndrome in vivo and was stable in a time-course experiment of biosynthesis in vitro. DNA polymerase chain reaction direct sequencing of the mutated gene from 135 nt upstream of the cap site to 106 nt downstream of the polyadenylation site showed only the beta 126 GTG----GGG mutation, which was confirmed in the other patients by allele-specific oligonucleotide hybridization. The mutation was found to be associated with a type II beta-globin framework and restriction fragment length polymorphism haplotype V. The novel variant was named hemoglobin Neapolis.
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PMID:Hemoglobin Neapolis, beta 126(H4)Val----Gly: a novel beta-chain variant associated with a mild beta-thalassemia phenotype and displaying anomalous stability features. 195 92

beta-Thalassemia minor occurs at approximately 1% frequency in French-Canadians--in families residing in Portneuf County (population approximately 40,000) of Quebec province. We found eight different RFLP haplotypes at the beta-globin gene cluster in 37 normal persons and in 12 beta-thalassemia heterozygotes from six families. beta-Thalassemia genes in these families associated with two haplotypes only: Mediterranean I and Mediterranean II. There were two different beta-thalassemia mutations segregating in the Portneuf population: an RNA processing mutation (beta(+)IVS-1,nt110) on haplotype I (five families) and a point mutation leading to chain termination (beta(0) nonsense codon 39) on haplotype II (one family). The distribution of 5' haplotypes on normal beta A Portneuf chromosomes compared with other European populations was most similar to that in British subjects (data for French subjects have not yet been reported). Genealogical reconstructions traced the ancestry of carrier couples to settlers emigrating from several different regions of France to New France in the 17th century. These findings indicate genetic diversity of a greater degree among French-Canadians than recognized heretofore.
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PMID:Beta-thalassemia genes in French-Canadians: haplotype and mutation analysis of Portneuf chromosomes. 196 5

We have identified the substitution of a thymine for a cytosine at nucleotide position 654 in the second intron of the beta-globin gene that causes beta-thalassemia in a Japanese family. This mutation was reported to occur rather frequently in patients of Chinese origin, but has rarely been found in other ethnic groups.
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PMID:A common Chinese beta-thalassemia mutation found in a Japanese family. 196 46

Analysis of the molecular basis of dominantly inherited beta-thalassemia in four families has revealed different mutations involving exon 3 of the beta-globin gene. It is suggested that the phenotypic difference between this condition and the more common recessive forms of beta-thalassemia lies mainly in the length and stability of the abnormal translation products that are synthesized and, in particular, whether they are capable of binding heme and producing aggregations that are relatively resistant to proteolytic degradation.
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PMID:Molecular basis for dominantly inherited inclusion body beta-thalassemia. 197 Nov 9

Thirty-six pregnancies in 25 families at risk of beta-thalassaemia major received prenatal diagnosis. Chorionic villus sampling or amniocentesis was done in 35 pregnancies to obtain fetal cells for DNA linkage study, for which Southern blotting and DNA hybridization were used to detect seven restriction fragment length polymorphisms (RFLPs) within the beta-globin gene cluster: epsilon-HincII, G gamma-HindIII, A gamma-HindIII, phi beta-HincII, 3' phi beta-HincII, beta-AvaII, and 3' beta-BamHI. beta-Thalassaemia major was diagnosed in seven and excluded in 22 pregnancies. In the remaining six cases, beta-thalassaemia major could not be excluded. In these six pregnancies and another one with late booking, ultrasound-guided cordocentesis was performed at the 22nd to 27th week of gestation. Globin chain composition was determined with urea-acetic acid-Triton X-100-12 per cent polyacrylamide gel electrophoresis. beta-Thalassaemia major was diagnosed in two fetuses and excluded in the other five. Eleven fetuses (in which beta-thalassaemia major was excluded) have been delivered and are healthy at more than 5 months old. DNA linkage analysis coupled with globin chain electrophoresis provides an effective way for prenatal diagnosis of beta-thalassaemia major, although these methods are being replaced by more direct detection techniques using oligonucleotide probes.
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PMID:DNA polymorphism and globin chain analysis in the prenatal diagnosis of beta-thalassaemia major in Taiwan. 197 94

Amplification of DNA via polymerase chain reaction directly from a small amount of a buffy coat fraction was used to study the molecular basis of HbE-beta-thalassemia in the northeastern Thai population. Eight different mutations including the new one causing a beta o-thalassemia phenotype were detected. This novel mutation is an amber mutation at codon 26, which occurs at the same position as that of HbE; the most common hemoglobin variant in Southeast Asian countries. A pitfall in detection of the HbE mutation by restriction enzyme analysis was pointed out and differential diagnosis of the HbE mutation and the novel one by using allele specific oligonucleotide probes were described. Analysis of polymorphic restriction sites in the beta-globin gene cluster containing the beta E gene revealed two previously undescribed haplotypes in the Southeast Asian populations, which provide evidence for the multiple origins of beta E gene in Southeast Asian populations.
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PMID:Molecular basis of HbE-beta-thalassemia and the origin of HbE in northeast Thailand: identification of one novel mutation using amplified DNA from buffy coat specimens. 197 22


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