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

The predominant beta-thalassemia in Sardinia is the beta 0 type in which no beta-globin chains are synthesized in the homozygous state. We determined the beta-thalassemia mutations in this population by the oligonucleotide-probe method and defined the chromosome haplotypes on which the mutation resides. The same beta 39(CAG----TAG) nonsense mutation was found on nine different chromosome haplotypes. Although this mutation may have arisen more than once, the multiple haplotypes could also be generated by crossing over and gene conversion events. These findings underscore the frequency of mutational events in the beta-globin gene region.
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PMID:The same beta-globin gene mutation is present on nine different beta-thalassemia chromosomes in a Sardinian population. 303 68

We have identified a beta-thalassemia gene that carries a novel nonsense mutation in a Chinese patient. This mutation, a G to T substitution at the first position of codon 43, changes the glutamic acid coding triplet (GAG) to a terminator codon (TAG). Based on oligonucleotide hybridization studies of 78 Chinese and Southeast Asian beta-thalassemia chromosomes, we estimate that this mutation accounts for a small minority of the beta-thalassemia mutations in that population. Study of the expression of this cloned gene in a transient expression system demonstrated a 65% decrease in levels of normally spliced mutant beta-globin mRNA. However, the study of reticulocyte RNA isolated from an individual heterozygous for this mutation demonstrated a total absence of this mutant mRNA in vivo. The basis for this big discrepancy between the level of accumulated mRNA in vivo and in vitro is probably the result of differences in the stabilities of the mutant mRNA in erythroid cells.
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PMID:New amber mutation in a beta-thalassemic gene with nonmeasurable levels of mutant messenger RNA in vivo. 340 16

Selective overexpression (50- to 100-fold) in adult erythroid cells of either G gamma or A gamma fetal globin gene is observed in hereditary conditions known as delta beta zero-thalassemia and hereditary persistence of fetal hemoglobin (HPFH). Recently, a C----T change at position -196 of an overexpressed A gamma globin gene from an Italian HPFH was hypothesized, on the basis of indirect evidence, to represent the cause of the functional defect. We now show that the same mutation is present in a different overexpressed A gamma-globin gene from a Sardinian patient with a different syndrome (delta beta zero-thalassemia). The Sardinian A gamma globin gene differs from both the HPFH and the normal A gamma globin gene at nucleotide 1,560 in the noncoding portion of the third exon, where an A is deleted. In addition, the mutant -196 A gamma-globin gene is linked to a normal beta globin gene in HPFH, and to a beta-thalassemic gene (beta 39CAG----TAG) in delta beta zero-thalassemia. These data strengthen the suggestion that -196 mutation is causally linked to the abnormal phenotype and raise the question of whether the same or multiple mutational events are responsible for the appearance of the -196 mutation in different syndromes.
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PMID:Sardinian delta beta zero-thalassemia: a further example of a C to T substitution at position -196 of the A gamma globin gene promoter. 382 30

Two beta globin genes from patients with the beta(+) thalassemia phenotype have been cloned and sequenced. A single nucleotide change from CAG to TAG (an amber mutation) at codon 39 is the only difference from normal in both genes analyzed. The results are consistent with the assumption that both patients are doubly heterozygous for beta(+) and beta degrees thalassemia, and that we have isolated and analyzed the beta degrees thalassemia gene.
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PMID:Two cloned beta thalassemia genes are associated with amber mutations at codon 39. 627 53

Superoxide anion production in resting and PMA- or zymosan-stimulated neutrophils was evaluated in 21 beta-thalassemia patients. The results were correlated with ferritin values, hepatitis B virus serum markers, liver pathology, immunoglobulin levels and T-cell subsets. Superoxide anion generation from resting or PMA-stimulated neutrophils was significantly higher in patients than in controls. On the contrary, zymosan-stimulated neutrophils showed reduced superoxide anion production. Increased superoxide anion production in resting neutrophils showed a significant correlation to the values of ferritin. In addition, patients with biopsy-proven chronic liver disease showed significantly increased ferritin levels and superoxide anion production as compared to the remaining patients. No correlation was observed between superoxide anion production and the presence or the absence of hepatitis B virus serum markers, immunoglobulin levels and T-cell subsets. A possible role of interreactions between iron and oxygen radicals in determining liver damage in beta-thalassemia patients is suggested.
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PMID:Changes in superoxide anion production in neutrophils from multitransfused beta-thalassemia patients: correlation with ferritin levels and liver damage. 633 Oct 44

We investigated a method employing synthetic oligonucleotides for the prenatal diagnosis of beta-thalassemia due to a single nucleotide mutation. The beta 0 thalassemia we tested is produced by a nonsense mutation and is commonly found in Sardinia and other parts of the Mediterranean. In this DNA lesion, the glutamine codon CAG at the beta 39 position is mutated to TAG, which results in a stop codon and premature termination of the beta-globin chain. We synthesized two oligonucleotides: one homologous to the normal beta A gene and the other to the beta 0 thalassemia gene at the beta 39 location. The oligonucleotides were labeled with 32P and used as hybridization probes for normal and thalassemic DNA. The beta A probe hybridized only to the normal DNA, and the beta-thalassemia probe only to thalassemic DNA, thus providing a technique for direct demonstration of the mutation. The method is sensitive enough to be applied directly to DNA that is isolated from uncultured cells obtained from only 20 ml of amniotic fluid as early as the 16th gestational week.
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PMID:Prenatal diagnosis of beta-thalassemia. Detection of a single nucleotide mutation in DNA. 686 53

Hb Lulu Island [beta 107(G9)Gly-->Asp] was discovered in an East Indian female who carried a common beta zero-thalassemia allele, i.e., codon 15, TGG-->TAG (is a stop codon) in trans. Both abnormalities were detected through sequencing of the amplified beta-globin genes and were confirmed by hybridization with 32P-labeled probes. Hb Lulu Island is mildly unstable with a borderline decrease in oxygen affinity; its instability is less severe than that of Hb Burke or beta 107(G9)Gly-->Arg. The compound heterozygosity expresses as a thalassemia intermedia with moderate anemia, a variable need for blood transfusions, Heinz body formation, and a red cell morphology which is typical for such a condition. The level of HbA2 was greatly increased (6.5-7.0%) as was the delta chain level (12% of total non-alpha) probably because of the instability of Hb Lulu Island and the decreased ability of the beta x chain to form dimers with the normal alpha chain.
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PMID:Hb Lulu Island (alpha 2 beta 2 107[G9]Gly-->Asp)-beta zero- thalassemia (codon 15; TGG-->TAG), a form of thalassemia intermedia. 766 21

A novel amber mutation, a G to A substitution at the second position of codon 37 in the beta-globin gene that changes the tryptophan coding triplet (TGG) to a termination codon (TAG), was found in a Chinese beta-thalassaemia carrier. The mutant gene creates an additional Dde I recognition site and eliminates the Ava II site, so this point mutation can be directly identified by restriction enzyme analysis.
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PMID:A novel amber mutation in a beta zero-thalassaemia gene (beta 37TGG-->TAG), with direct detection by mapping the restriction fragments in amplified genomic DNA. 766 81

Forty-one cases of beta-thalassemia major were assessed for their clinical manifestations and gene mutation. The age distribution was from 1 to 18 years old. Patient's initial clinical symptoms began mostly before 2 years of age (90.2%). Patient's initial hematological data included mean hemoglobin value, 5.8 +/- 1.2 gm/dl, hemoglobin F value, 85.0 +/- 12.1%, hemoglobin A2 value 2.3 +/- 1.8%, reticulocyte count 9.2 +/- 9.0%. Eight different point mutations were characterized. Of these mutations, C to T substitution at nucleotide (nt) 654 of intervening sequence (IVS) 2, accounting for 46.3% of mutant beta-globin genes, is the most common mutation in our series, followed by frameshift codons 41/42 with a four nucleotides (TCTT) deletion for 31.7%; A to G substitution at position -28 of the promotor area for 8.5%; A to T substitution at codon 17 for 6.1%; frameshift codons 27/28 (insertion of C) for 2.4%; G to T substitution at nucleotide 1 of IVS-1 for 2.4%; frameshift codons 71/72 (insertion of A) and IVS-1 3' end TAG-->GAG for 1.2%. The first four mutations account for 92.6% of all beta-globin gene mutations in our series. As to mutations in each individual, the incidence of compound heterozygotes of two different mutations is much higher than homozygotes of a single mutation, 78.0% vs. 22.0%. Compound heterozygotes of C to T substitution at nt 654 of IVS-2 and frameshift codons 41/42 with a four nucleotides deletion is the most common pattern of beta-thalassemia mutation in our patients (41.5%). Patients with beta(0)/-28 beta(+) compound heterozygote mutation had much delayed initial symptoms than beta (0)/beta(0) homozygote mutation, but clinical manifestation may be aggravated when the mutation combined with glucose-6-phosphate dehydrogenase deficiency. Severity of iron overload was significantly correlated with total transfusion amount and patient's age in simple regression analysis (p < 0.001). Splenectomy may effectively prolong transfusion interval, maintain higher hemoglobin level before each transfusion and palliate clinical symptoms (p < 0.01). Iron-chelating agent therapy can effectively lower the total amount of serum ferritin. Higher severity of iron overload correlates with higher incidence of EKG and cardiac abnormalities in patients with beta-thalassemia major.
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PMID:[Current clinical approaches and gene mutation study of beta-thalassemia major]. 770 61

beta-Thalassaemia major patients have chronic anaemia and since 3-4 per cent of Singaporeans carry the beta-gene, prenatal diagnosis is essential. We evaluated the amplification refractory mutation system (ARMS) technique as a routine test for prenatal diagnosis of beta-major. Six mutations along the beta-gene were studied--41-42 (-TCTT), IVSII #654 (C-T), 17 beta (A-T), -28 TATA (A-G), IVSI #5 (G-C), and IVSI #1 (G-T). Our results indicate that prenatal diagnosis using these mutations can be offered to 90 per cent (35/39) of our Chinese couples and 54.6 per cent (12/22) of our Malay couples at risk. Confirmation of ARMS results was carried out using allele-specific oligonucleotide hybridization. Prenatal diagnosis using ARMS was successfully carried out in nine cases which included a set of triplets and twins. The triplets were diagnosed with the beta-trait carrying the 41-42 mutation. The couple with twins possessed the #654 mutation and one twin was diagnosed with the beta-trait and the other with #654 homozygosity. Genomic sequencing of the undefined mutations in the Chinese couples revealed rarer mutations at -29 and an ATG-AGG base substitution at the initiation codon for translation. In the Malay couples, genomic sequencing detected mutations at codon 15 (TGG-TAG) and codon 26 (GAG-AAG). We conclude that ARMS with its direct detection of amplified products by gel electrophoresis provides an accurate, rapid, and simpler method for our beta-thalassaemia prenatal diagnosis programme in Singapore.
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PMID:The amplification refractory mutation system (ARMS): a rapid and direct prenatal diagnostic technique for beta-thalassaemia in Singapore. 787 57


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