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)

A free radical is any species capable of independent existence that contains one or more unpaired electrons. Free radical reactions have been implicated in the pathology of more than 50 human diseases. Radicals and other reactive oxygen species are formed constantly in the human body, both by deliberate synthesis (e.g. by activated phagocytes) and by chemical side-reactions. They are removed by enzymic and nonenzymic antioxidant defence systems. Oxidative stress, occurring when antioxidant defences are inadequate, can damage lipids, proteins, carbohydrates and DNA. A few clinical conditions are caused by oxidative stress, but more often the stress results from the disease. Sometimes it then makes a significant contribution to the disease pathology, and sometimes it does not. Several antioxidants are available for therapeutic use. They include molecules naturally present in the body [superoxide dismutase (SOD), alpha-tocopherol, glutathione and its precursors, ascorbic acid, adenosine, lactoferrin and carotenoids] as well as synthetic antioxidants [such as thiols, ebselen (PZ51), xanthine oxidase inhibitors, inhibitors of phagocyte function, iron ion chelators and probucol]. The therapeutic efficacy of SOD, alpha-tocopherol and ascorbic acid in the treatment of human disease is generally unimpressive to date although dietary deficiencies of the last two molecules should certainly be avoided. Xanthine oxidase inhibitors may be of limited relevance as antioxidants for human use. Exciting preliminary results with probucol (antiatherosclerosis), ebselen (anti-inflammatory), and iron ion chelators (in thalassaemia, leukaemia, malaria, stroke, traumatic brain injury and haemorrhagic shock) need to be confirmed by controlled clinical trials. Clinical testing of N-acetylcysteine in HIV-1-positive subjects may also be merited. A few drugs already in clinical use may have some antioxidant properties, but this ability is not widespread and drug-derived radicals may occasionally cause significant damage.
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PMID:Drug antioxidant effects. A basis for drug selection? 172 62

During the past 15 years there have been remarkable advances in our understanding of the molecular biology of hemoglobin synthesis and the abnormalities in hemoglobinopathies and thalassemia. The globin genes were among the first mammalian structural genes that were cloned and the DNA sequence of the human globin gene clusters has since been completely delineated. During the last ten years, we have also learned of the many deletions and point mutations that give rise to hemoglobin-opathies and thalassemia. In addition, the sequences that control erythroid specific expression of the globin gene has also been revealed. These findings have contributed to our understanding of the pathophysiology of the diseases and have allowed the institution of accurate DNA diagnostic methods to be applied to prenatal diagnosis. As increased fetal hemoglobin synthesis is known to ameliorate the severity of the disease in disorders such as sickle cell anemia and thalassemia, agents which increase the level of fetal hemoglobin synthesis are being tested. Also, the discovery of DNA sequences and transacting factors which are responsible for high erythroid globin gene expression [4] may provide more effective means of gene therapy.
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PMID:Molecular biology of hemoglobin: its application to sickle cell anemia and thalassemia. 172 57

This study reports the molecular characterization of beta-thalassemia in the Sardinian population. Three thousand beta-thalassemia chromosomes from prospective parents presenting at the genetic service were initially analyzed by dot blot analysis with oligonucleotide probes complementary to the most common beta-thalassemia mutations in the Mediterranean at-risk populations. the mutations which remained uncharacterized by this approach were defined by denaturing gradient gel electrophoresis (DGGE) followed by direct sequence analysis on amplified DNA. We reconfirmed that the predominant mutation in the Sardinian population is the codon 39 nonsense mutation, which accounts for 95.7% of the beta-thalassemia chromosomes. The other two relatively common mutations are frameshifts at codon 6 (2.1%) and at codon 76 (0.7%), relatively uncommon in other Mediterranean-origin populations. In this study we have detected a novel beta-thalassemia mutation, i.e., a frameshift at codon 1, in three beta-thalassemia chromosomes. The DGGE procedure followed by direct sequencing on amplified DNA is a powerful approach for the characterization of unknown mutations in this genetic system. The results herein presented allowed an expansion of the applicability of prenatal diagnosis by DNA analysis, to all couples at risk for beta-thalassemia in our population.
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PMID:Molecular characterization of beta-thalassemia in the Sardinian population. 173 21

We have identified different beta-thalassemia mutations in 93 members of 34 families of Czech or Slovakian descent using gene amplification, hybridization with specific 32P-labeled oligonucleotide probes, sequencing of amplified DNA, and gene mapping. The G----A mutation at IVS-I-1 was found in 18 families; other Mediterranean mutations were IVS-II-1 (G----A), IVS-II-745 (C----G), IVS-I-110 (G----A), and codon 39 (C----T); these were present in 9 additional families. The G----T mutation at codon 121, known to cause Heinz-body beta-thalassemia, was present in 3 families, and the frameshift at codons 82/83 (-G), first described in the Azerbaijanian population, in 2 families. A newly discovered allele was a frameshift at codons 38/39 (-C). One beta-thalassemia allele was incompletely characterized. We observed in 2 families a T----C mutation at position +96 UTR (untranslated region) relative to the termination codon; this mutation likely is a rare polymorphism. alpha-Thalassemia was rare; only one person carried the -alpha 3.7 heterozygosity, and one other had a yet to be identified alpha-thalassemia-1, while seven had the alpha alpha alpha anti 3.7 triplication.
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PMID:Molecular characterization of beta-thalassemia in Czechoslovakia. 174 Mar 17

The molecular basis of most beta-thalassemia syndromes has been defined, while the spectrum of mutations causing delta-thalassemia is not well characterized. In an attempt to identify such mutations, the region encompassing the delta-globin gene from three Greek Cypriot families suspected of having delta-thalassemia was amplified by polymerase chain reaction (PCR), and DNA sequence determined using an automated fluorescence-based sequencer. Four novel mutations were identified: a G----T change at codon 27 that results in an alanine to serine change; a C----T change at codon 116 converting arginine to cysteine; a T----C change at codon 141 converting leucine to proline; and an AG----GG change at the consensus 3'-acceptor site in IVS-2. While the latter is clearly a thalassemic mutation, the low hemoglobin A2 in the first three may be due to either decreased production or instability of the altered delta-globin chain. All four mutations may be detected by PCR amplification of genomic DNA followed by restriction enzyme digestion. Two mutations abolish restriction sites while two create new cleavage sites. Screening for molecular defects that cause delta-thalassemia or unstable delta-globin by PCR amplification and restriction enzyme digestion will lead to correct diagnosis of beta/delta-thalassemia compound heterozygotes and improved genetic counseling.
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PMID:Identification of four novel delta-globin gene mutations in Greek Cypriots using polymerase chain reaction and automated fluorescence-based DNA sequence analysis. 174 90

The aim of this study was to determine the crude prevalence of alpha-thalassemia traits in Taiwan. A total of 1435 healthy employees from a statewide company were randomly screened by complete blood count determination with indices. Subjects with mean corpuscular volume less than 80 fl were analyzed by hemoglobin electrophoresis on cellulose acetate to exclude beta-thalassemia and with serum ferritin to exclude iron deficiency. Modified hemoglobin H inclusion staining was performed to confirm the diagnosis of alpha-thalassemia traits, and DNA probe studies were used to confirm the validity of this test. The overall prevalence rate of alpha-thalassemia trait was 3.4% (48 out of 1435). In persons of mainland Chinese origin, prevalence was 0.4%, and among persons of Taiwanese origin, it was 4.0% (47 out of 1171). We conclude that alpha-thalassemia traits are common genetic disorders in Taiwan and that antenatal screening is advised to reduce the frequency of occurrence of hemoglobin Bart's hydrops fetalis. The methods we used proved to be reliable and inexpensive.
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PMID:Alpha-thalassemic traits are common in the Taiwanese population: usefulness of a modified hemoglobin H preparation for prevalence studies. 174 8

Gene amplification by the polymerase chain reaction (PCR) has been applied to prenatal diagnosis for alpha and beta thalassemias (1 and 5 cases respectively), Hemoglobin (Hb) Lepore/beta thalassemia (1 case) and cystic fibrosis (14 cases). Chorionic villus samples were obtained in the tenth week of pregnancy and DNA analysed in parallel with conventional gene mapping. Direct diagnosis of the common Mediterranean beta-thalassemia mutations (IVS-1-110 and codon 39), Hb Lepore, and the delta F508 mutation causing cystic fibrosis was achieved by hybridization of amplified material with pairs of allele-specific oligonucleotide (ASO) probes or by restriction enzyme digestion of PCR products. Results were confirmed by DNA mapping. Definitive diagnosis or exclusion of an affected fetus was possible in 17 of 21 cases thus examined. PCR reduces the time required for prenatal diagnosis. DNA contamination is a potential source of error.
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PMID:Utility of the polymerase chain reaction (PCR) for prenatal diagnosis of genetic disease. 174 68

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

An etiological examination was performed on the DNA of a 13-year-old Zairean girl, who had some abnormalities in hematological and red cell morphological examinations and was homozygote for an abnormal Hb like HbS. DNA was amplified by the PCR method to obtain 1.7 kb size DNA containing the 5' region of the beta globin gene. The amplified DNA was digested with Eco 81 I and electrophoresis of the digest revealed the absence of its active site, which is on codons beta 5-7 (CCTGAGGAG) of the normal DNA. Sequencing of the cloned DNA by the dideoxy method confirmed that the codon beta 6 (GAG, Glu) mutated to a new codon GTG (Val) which is the beta S globin gene producing abnormal HbS. The haplotype of the chromosome having beta S gene was --+---++, which is the most common type in Zaire area. On the other hand, when the genomic DNA was digested with Bgl II or Bam HI and hybridized to an alpha probe, a fragment (16 kb/Bgl II or 10.5 kb/Bam HI) in addition to the normal ones (12.5 and 7.5 kb/Bgl II or 14 kb/Bam HI) was observed. This resulted from the deletion of 3.7 kb from the alpha gene arrangement, which led to alpha-thalassemia-2 (genotype: alpha 3.7-/alpha alpha). A family study demonstrated that her parents were heterozygote for HbS and her father had alpha-thalassemia-2.
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PMID:[Molecular analysis of an African family with sickle cell disease and alpha-thalassemia-2]. 177 70

Beta-thalassemia minor occurs at 5% frequency (on average) in populations migrant (since 1945) from Mediterranean countries to the province of Quebec. Individuals of Southeast Asian/Chinese and Asian Indian origin now living in the province also carry beta-thalassemia genes at similar frequencies. We characterized beta-thalassemia genes on 68 chromosomes (19 patients and 30 carriers identified by screening) to describe heterogeneity of beta-thalassemia alleles and to evaluate desirability of DNA tests in carrier screening. Thirteen different mutations account for 74% of the 68 beta-thalassemia chromosomes: seven occur on Mediterranean chromosomes (IVS I,nt110, Non 39, IVS I,nt6, IVS I,nt1G----A, IVS II,nt1, Fr8, IVS II,nt745) another three on SE Asian chromosomes (Fr 41-42, IVS II,nt654, HbE) and yet another three on Asian Indian chromosomes (IVS I,nt5, 619 bp del, IVS I,nt1G----T). Twenty-six percent (18/68) of the chromosomes carried none of 17 alleles accounting for 92-96% of beta-thalassemia molecular pathology in reference populations. The Italian beta-thalassemia chromosomes in the Quebec sample least resembled those in the corresponding source population. Until the spectrum of mutations in Quebec populations is fully defined, phenotype assay remains the most reliable and efficient method for beta-thalassemia carrier screening.
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PMID:Quantitation of beta-thalassemia genes in Quebec immigrants of Mediterranean, southeast Asian, and Asian Indian origins. 178 30


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