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)

In this study, we have defined the beta thalassemia mutation and characterized the beta globin haplotype and the alpha globin gene arrangement in a group of patients of Sicilian descent with beta (s)/beta thalassemia. We found that those patients carrying a beta(+) thalassemia mutation associated with a moderate reduction of beta chain synthesis (beta(+) IVS-1 nt 6) have normal or reduced Hb levels and mild to moderate clinical manifestations, as defined by the number of hospital admission and sickle cell crises per year. Those patients carrying a beta(+) thalassemia mutation associated with a severe reduction of beta chain synthesis (beta(+) IVS-1 nt 110) have a disease of moderate severity. In those carrying a beta(0) thalassemia gene the disease was clinically very heterogeneous, ranging in severity from mild to severe with no difference related to the type of mutation [beta(0) 39, beta(0) IVS-1 nt 1, beta(0) IVS-2 nt 1, beta(0) 6 (-1bp)]. In this last group of patients part of the clinical variability may be attributed to the HbF levels, which were higher in those with mild to moderate clinical severity.
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PMID:The effect of the beta thalassemia mutation on the clinical severity of the sickle beta thalassemia syndrome. 250 7

Six beta(+)-thalassaemic patients from the Po river delta region have been studied. Using synthetic oligonucleotides as specific hybridisation probes, the beta(+) IVS I mutation (G----A at position 108) was demonstrated. This lesion and the enzyme polymorphism pattern in the subjects examined are the same as have been described for other Mediterranean beta(+)-thalassaemias. Antenatal diagnosis through DNA analysis of beta(+)-thalassaemia is therefore possible. The production of beta globin in a beta(+), homozygote and in a beta (+), beta(0) 39 (nonsense mutation at codon 39) double heterozygote is approximately 20% and 10% respectively of total non-alpha globin synthesis. Despite some overlapping of the results, similar beta globin synthesis levels have been obtained in 43 beta(+)-thalassaemia patients. This suggests that in the Po river delta region the most common thalassaemic genes are beta(0) 39 and beta(+) IVS I.
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PMID:beta (+)-Thalassaemia in the Po river delta region (northern Italy): genotype and beta globin synthesis. 258 95

Hemoglobin H disease is often caused by deletion of three of the four alpha-globin genes (genotype: --/-alpha). We studied a Japanese girl who had microcytic hypochromic anemia, a decreased alpha/beta globin synthetic ratio and about 8% Hb H in her fresh hemolysate, by means of restriction endonuclease mapping of the alpha-like gene complex (5'-zeta-phi zeta-phi alpha 2-phi alpha 1-alpha 2-alpha 1-theta-3') with zeta- and alpha-specific probes. It was found that the defect of one chromosome was associated with the removal of about 18 kb of DNA, known as --SEA type alpha-thalassemia-1, including the deletion of the part of phi alpha 2, phi alpha 1, alpha 2, alpha 1, and theta globin genes, while the other one was associated with the removal of 3.7 kb of DNA, known as rightward deletion type alpha-thalassemia-2. The results of a family study demonstrated that the deletion haplotype --SEA was inherited from her father's side and the other -alpha 3.7 from her mother's side.
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PMID:[The molecular basis of HbH disease in a Japanese girl]. 261 58

Human alpha-globin gene mapping was carried out using a variety of restriction endonucleases (Bgl II, Bam HI, Hind III, Eco RI, Hpa I, Pvu II and Rsa I) on members of a family from El Salvador and a female from Hawaii, of Chinese descent, whose hematological and clinical parameters were those of beta-thalassemia intermedia. Southern blot DNA analysis showed that the beta-thalassemia intermedia patients from the above two families had the same anti 3.7 type quadruplicated alpha-genes on the one chromosome, and that they had the alpha genotype alpha 2, alpha 1 alpha 2, alpha 1 alpha 2, alpha 1/alpha 2, alpha 1. The alpha/beta globin synthesis ratios of the three affected Salvadoran patients were around 2.5, and the affected Hawaiian patient was 2.9. These ratios strongly suggest that the additional alpha-genes in the anti 3.7 type rearrangement are biologically active, thus accounting for the severity of the heterozygous beta-thalassemia observed among these patients.
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PMID:The interaction of anti 3.7 type quadruplicated alpha-globin genes and heterozygous beta-thalassemia. 273 8

In the Mediterranean area, 50% of the beta thalassaemia mutations abolish or create a restriction endonuclease site in the beta globin gene. This study describes a new procedure for prenatal detection of these beta thalassaemia defects based on the direct visualisation, on an ethidium bromide stained polyacrylamide gel, of the discrete DNA fragments produced by restriction endonuclease digestion of fetal DNA, enzymatically amplified using the DNA polymerase from the thermophilus bacterium Thermus aquaticus. We applied this procedure to the Sardinian population to detect the nonsense mutation at codon 39 and the frameshift at codon 6 of the beta globin gene; these are the most frequent beta thalassaemia mutations in this population, accounting for 95% and 2.2% of the beta thalassaemia chromosomes. The main advantages of this procedure are simplicity (no radioactivity), sensitivity (0.2 microgram of DNA), and rapidity (12 hours). The very small amount of fetal material required makes amniotic fluid cell culture unnecessary and may decrease the fetal loss rate associated with trophoblast sampling. By circumventing the use of radioactive and non-radioactive probes, the spread of this technology to the high risk areas will be facilitated.
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PMID:Prenatal diagnosis of beta thalassaemia based on restriction endonuclease analysis of amplified fetal DNA. 273 98

Clinical, hematologic and hemoglobin composition data on the first case of Hb 0-Arab in association with beta 0-thalassemia in Yugoslavia are reported here. The propositus was a 26-years-old female from Strumica who was admitted to the hospital for several times because of anemia, hepatosplenomegaly, occasional abdominal pains, malaise and fatigue. Laboratory results presented: Hb 10.0 g/dl, RBC 3.84.10(12)/L, PCV 0.260 l/l, MCV 68 fl, MCH 26 pg, reticulocyte count 1.8%, anisopoikilocytosis, polychromasis, numerous target cells, total bilirubin 2.1 mg/dl, (indirect 1.7 mg/dl), serum-Fe 32.3 microM/L. A starch gel electrophoresis of hemolysate provided evidence for the presence of abnormal hemoglobin (approximately 85%) and Hb F (approximately 15%); the Hb A was absent. Familial screening showed her father was heterozygous for the abnormal hemoglobin, whereas the mother was heterozygous for beta-thalassemia. In vitro biosynthesis disclosed a total absence of beta globin and reduced synthesis of beta x x and gamma globin. The alpha/beta x + gamma-globin ratio was 1.77 (normal, 1.0 + 0.1). Amino acid analysis revealed that lysine substituted for glutamic acid at the position one hundred twenty-one of the beta chain (= Hb 0-Arab or beta 121 Glu----Lys).
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PMID:[Hemoglobin O Arab in interaction with beta 0-thalassemia]. 273 98

The Corfu delta beta zero thalassemia is characterized by the clinical picture of thalassemia intermedia. In the homozygous state there is a complete absence of hemoglobin (Hb) A and Hb A2 and a high level of Hb F. A DNA fragment containing the gamma and beta globin genes has been cosmid cloned, and the deletion breakpoint region, the beta globin gene and the promoter regions of the gamma globin genes sequenced. The deletion removes 7,201 base pairs (bp) containing part of the delta globin gene and sequences upstream. The beta globin gene contains a G----A mutation at IVS 1 position 5. The gamma globin gene promoters are normal. Analysis of the transcription of the mutated beta globin gene in transfected HeLa cells shows that normal message is produced at a level of approximately 20% compared with a normal gene, the remaining 80% being spliced at cryptic sites in exon 1 and intron 1. This indicates that the mutation in the beta globin gene is not the sole cause of the absence of Hb A in Corfu delta beta zero thalassemia. It is concluded that the 7.2 kilobase (kb) of deleted DNA contains sequences necessary for the normal activation of the beta globin gene. Possible mechanisms for the effect of the deletion on the expression of beta and gamma globin genes are discussed.
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PMID:The Corfu delta beta zero thalassemia: a small deletion acts at a distance to selectively abolish beta globin gene expression. 282 15

Restriction endonuclease mapping analyses were made of DNA from a few members of a Macedonian family with hematological characteristics of delta beta-thalassemia, ie, microcytosis, normal HbA2 levels, and elevated levels of HbF (7% to 14%) with G gamma (average 40.5%) and A gamma T chains (average 59.5%). A large deletion of 18 to 23 kb was present with a 5' breakpoint within a 670-bp segment of DNA between the HpaI and NcoI restriction sites 5' to the delta globin gene, and a 3' breakpoint between the BamHI and HpaI restriction sites located some 9 to 13 kb 3' to the beta globin gene. This deletion is different from those present in other types of G gamma A gamma(delta beta)zero-thalassemia. The similarity of the hematological expression of these delta beta-thalassemic conditions which have somewhat comparable 5' breakpoints supports the idea that an important fetal hemoglobin-controlling region lies between the psi beta and delta globin genes.
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PMID:The 18- to 23-kb deletion of the Macedonian delta beta-thalassemia includes the entire delta and beta globin genes. 287 56

The beta globin haplotypes, corresponding to 50 normal and 50 thalassaemic chromosomes, were determined in 25 families from the Po river delta area who had beta thalassaemia. The haplotypes were obtained by studying the familial segregation of 6 restriction fragment length polymorphisms of the beta globin gene cluster. The results show an almost exclusive presence of 3 haplotypes linked to the beta thalassaemia chromosomes of this area: haplotype I, II and IX according to Orkin's classification. It is therefore possible that only two thalassaemic mutations are present. A wider variety of haplotypes was found to be linked to normal chromosomes. Prenatal diagnosis, by the analysis of polymorphic sites (the 6 plus one other) was possible in 92% of the cases. The probable high homogeneity of the molecular mutations makes the use of specific oligonucleotides practical and applicable to prenatal diagnosis.
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PMID:Haplotypes of thalassaemic families from the Po river delta: importance for prenatal diagnosis of beta-thalassaemia. 289 29

In the course of a prenatal diagnosis for beta thalassaemia by linkage analysis of restriction fragment length polymorphisms, a homozygous beta thalassaemia fetus was misdiagnosed as beta thalassaemia trait. Extensive studies of the polymorphic sites within the beta globin gene cluster in all the members of the family resulted in the conclusion that the paternal chromosome 11 of the newborn was different from that expected. Paternity was confirmed by HLA typing and blood group studies. The analysis of another polymorphic locus on chromosome 11 within the family was in agreement with the possibility of a crossing over between the two paternal chromosomes in a region 5' to the beta gene, previously indicated to contain a 'hot spot' area for recombination. This report underlines the risk of performing prenatal diagnosis using restriction polymorphisms 5' to the beta gene.
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PMID:Meiotic recombination in the beta globin gene cluster causing an error in prenatal diagnosis of beta thalassaemia. 289 35


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