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)

We have analyzed the hemoglobin abnormalities in nearly 50 Albanian patients with a significant hemoglobinopathy and included 37 relatives in this study. Sickle cell anemia (SS) is a common disorder; all 15 sickle cell anemia patients had the complications expected for this disease. The beta S haplotype was type 19 (Benin); alpha-thalassemia-2 was rare. Three beta-thalassemia alleles (IVS-I-110, G-->A; codon 39, C-->T; IVS-I-6, T-->C) were present in nearly 85% of the beta-thalassemia alleles; their frequencies were intermediate between those observed in the populations of neighboring countries. A few rare mutations were also found, which might have originated in India, Turkey, Macedonia, and Greece. Nearly all patients with Hb S-beta-thalassemia had the IVS-I-110 (G-->A) mutation. The frequencies of 11 beta-thalassemia mutations in 17 mostly Mediterranean countries have been reviewed.
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PMID:Sickle cell anemia, sickle cell beta-thalassemia, and thalassemia major in Albania: characterization of mutations. 811 43

Identification of the beta s gene cluster haplotype and alpha-gene status provides a useful tool for the detection of high-risk patients with sickle cell anemia. Analysis of the relationship of the long-term clinical course to the above parameters has revealed that those with the haplotype designated Senegal have decreased severity, those with the Benin haplotype have intermediate severity, and those with the Central African Republic (CAR) haplotype have the most severe clinical expression. Further modulation of the clinical course occurs with the coinheritance of alpha-thalassemia-2. In both Africa and the United States, the CAR beta s haplotype increased the risk (relative risk, 2.25; 95% confidence interval, 1.41 to 3.87) of developing a complication and death at an early age. Detection of the CAR haplotype identifies the child with sickle cell anemia at risk for a rapid rate of progression of sickle-induced microvasculopathy, ultimately leading to irreversible organ damage during the first three decades of life. In patients with the CAR haplotype, potential curative therapy, such as bone marrow transplantation or gene insertion, should be seriously considered during childhood, before organ failure is clinically evident.
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PMID:Sickle cell anemia. Beta s gene cluster haplotypes as genetic markers for severe disease expression. 823 15

The beta gene cluster haplotypes, alpha gene status, Hb F level and hematological parameters have been characterized in 154 unrelated Guadeloupe patients with sickle cell disease: 112 with sickle cell anemia, 26 with SC disease, 15 with Hb S-beta-thalassemia, and one patient with Hb S in association with the hereditary persistence of fetal hemoglobin. Fourteen haplotypes in 16 combinations were found, the three major African haplotypes were present on 92% of all chromosomes: 73% Benin, 11% Bantu, 8% Senegal. Among SS patients, 57% were Benin homozygotes, one patient was a Senegal homozygote, one patient was a Bantu homozygote, and all the others were heterozygous. The A gamma T chain was observed on seven chromosomes and about 5% of the analyzed beta S chromosomes exhibited atypical haplotypes. The common haplotype beta C was found in all patients with SC disease. An interesting feature was the high frequency (44%) of deletional alpha-thalassemia among SS patients. Two patients have an alpha-gene globin triplication. The DNA haplotypes and alpha-gene status have been correlated with hematological parameters in these patients. The anthropological aspect of these data is interesting as the haplotypes of the beta-globin gene throw light on the slave trade from the various parts of Africa to the Caribbean Islands in particular, and North America in general.
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PMID:beta S haplotypes, alpha-globin gene status, and hematological data of sickle cell disease patients in Guadeloupe (F.W.I.). 874 33

Admission records of children with sickle cell anemia (SS), in the two main teaching hospitals in Kuwait, were reviewed for a 1-year period. The haplotypes of 92 beta s chromosomes (from 39 SS, 11 AS, 2 S beta-thalassemia [S beta-thal] and 1 SD individuals) were determined using an allele-specific oligonucleotide (ASO) hybridization technique, while the alpha-globin gene status of 27 SS and 33 AS individuals, i.e. 120 chromosomes, was determined with a combination of polymerase chain reaction and AS techniques. A vasooclusive crisis was the most common (60.0%) cause of hospitalization, followed by infections (20%). Hospital admissions were most common during the hottest month of the year (July). Few complications of the disease were seen among patients on follow-up; however, splenomegaly was present in 24.0%, hepatomegaly in 15.2%, gallstones in 15.2% and aseptic necrosis of the femoral head in 6.1%. Haplotype 31 (Saudi Arabia/India) is the most frequent in this community, being present in 80.4% of the chromosomes tested; Benin haplotype 19 was found in 12.0% and Bantu haplotype 20 in 6.5%. Hb F in the haplotype 31 homozygotes and heterozygotes ranged from 11.4 to 35.1% (mean 22.5 +/- 5.2%). The frequency of alpha-thal determinants in the study was 40.0%, the commonest being the -alpha 3.7-kb deletion (27.5%), the alpha 2 polyadenylation signal (AATAAA-> AATAAG) mutation (10.2%) and the IVS-I 5' end GAGGT-GAGG->GAGG pentanucleotide (5 nt) deletion (3.3%). SS patients with coexistent alpha-thal trait did not have severe recurrent infections and none had gallstones. The high frequencies of the Saudi Arabia/India beta s haplotype and alpha-thalassemia trait contribute to the mild nature of SS disease among Kuwaiti Arabs comparable to that in eastern Saudi Arabia.
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PMID:Morbidity, beta S haplotype and alpha-globin gene patterns among sickle cell anemia patients in Kuwait. 887 12

To compare the features of sickle-cell anemia in Brazil with those in other locales, we studied the effects of the beta-globin-like gene cluster haplotype and alpha-thalassemia upon the clinical and hematological features in 85 patients. The distribution of haplotypes differed from that in the United States and Jamaica. The Central African Republic (CAR) haplotype predominated; 34% of patients were CAR haplotype homozygotes, 45% CAR/Benin homozygotes, and 11% Benin homozygotes. No Senegal haplotype chromosomes were observed. Alpha-thalassemia was present in 17.5% of patients. HbF levels were higher in Benin homozygotes, compared with the other two groups (P < 0.05). Nearly half the patients with a CAR haplotype had leg ulcers, compared to 12.5% of the Benin homozygote group; stroke did not occur in alpha-thalassemia carriers, but neither result was statistically significant. As in other studies, our results indicate that the CAR haplotype may be associated with more severe disease.
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PMID:Effect of alpha-thalassemia and beta-globin gene cluster haplotypes on the hematological and clinical features of sickle-cell anemia in Brazil. 889 30

We have studied haplotype of beta(S) chromosome and alpha-globin gene status in 534 patients (255 adults and 279 children of whom 159 neonates) from Guadeloupe with various sickle cell-related conditions, namely SS (n = 298), SC (n = 170), S-beta-thal (n = 56), and other rare forms (n = 10). Haplotype data on beta(S) chromosomes confirm our previous observation that Benin type is the most prevalent (75%) beta(S) chromosome in Guadeloupe, in disagreement with the historical records. Comparison of the frequency of distribution of various beta(S) haplotypes between neonates and adults on the one hand and between SS and SC cases on the other shows that the current beta(S) haplotype distribution in this island is not distorted by haplotype-related differential survival. We also show that the frequency of alpha-thalassemia (-3.7 kb) in Guadeloupe is one of the highest recorded in this region involved in Atlantic slave trade and also failed to reveal any age-dependent increase in frequency. We conclude that the African component of Guadeloupe is distinct from that of Brazil and Cuba but is close to that of Jamaica.
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PMID:Sickle cell disorder, beta-globin gene cluster haplotypes and alpha-thalassemia in neonates and adults from Guadeloupe. 913 13

Expression of fetal hemoglobin (Hb F) is under polygenic control involving determinants both linked and unlinked to the beta-globin gene cluster on chromosome 11. Variations in the DNase I-hypersensitive site 2 of the locus control region (LCR-HS2) and a C --> T change at position -158 from the Ggamma-gene (detected as an XmnI polymorphism) correlate with the high level of Hb F expression in patients with sickle-cell anemia and beta-thalassemia. Interpretation of data under these conditions of anemic stress is difficult because the preferential survival of Hb F-containing erythrocytes (F-cells) may not reflect the true status of Hb F expression. We investigated the relationship between these markers and Hb F expression in terms of F-cell levels in 48 unrelated non-anemic AS heterozygotes from Sicily. The betaS-chromosome of all these individuals was of the Benin haplotype and they differed only by their betaA chromosomes. We demonstrate that F-cell expression is more strongly associated with LCR-HS2 polymorphism than with XmnI polymorphism. The observed association between XmnI polymorphism and Hb F expression is very likely to be due to linkage disequilibrium with LCR-HS2 sequences.
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PMID:Dissection of the association status of two polymorphisms in the beta-globin gene cluster with variations in F-cell number in non-anemic individuals. 939 85

The link between beta s-gene haplotypes and sickle cell anemia has permitted a better understanding of the biological manifestations of this disease. The use of better laboratory methods can help rule out other hereditary factors that can camouflage the real hemoglobin genotype. The clinical heterogeneity of sickle cell disease, which is characterized by the presence of S hemoglobin, can be explained in terms of fetal hemoglobin (HbF) levels, ratio of G gamma chains to A gamma chains, 2,3-diphosphoglycerate levels, linked mutations, beta s haplotypes, coexistence of alpha-thalassemia, and environmental factors. The inheritance of Sen and Arab/Indian beta-gene cluster polymorphisms is associated with a milder clinical course, whereas the Central African Republic (CAR) or Bantu, Cameroon, and Benin haplotypes are linked with severe sickle cell disease. The CAR haplotype carries the worst prognosis of all (less than 12% HbF levels and adult-type G gamma:A gamma ratio). Once characterized, these DNA polymorphisms also assume great importance as anthropologic and genetic markers. In America, beta s haplotypes are contributing to a better understanding of Black American roots and their African ancestry. There is ample evidence of genetic variability not only between different Black populations in America, but also within the same country, as is the case in Costa Rica.
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PMID:[Hemoglobin S haplotypes: their epidemiologic, anthropologic and clinical importance]. 950 56

We have identified the beta s-globin gene haplotypes of 85 patients with sickle cell disease attending the Dubai Thalassemia Center and assessed the influence of haplotype, alpha-thalassemia, and fetal hemoglobin on the clinical presentation. Identification of the beta s haplotypes was based on mutation analyses in the promoter sequences of the G gamma- and A gamma-globin genes. The Arabian-Indian haplotype was found in 52% of the beta s chromosomes, whereas the remaining were the Bantu and Benin haplotypes. Those with the Arabian-Indian haplotype in this group had a significantly higher fetal hemoglobin (Hb F) level (mean 27%) and a milder clinical course. In contrast, those with the African haplotypes, Bantu and Benin, expressed relatively lower Hb F levels (mean 11.3%), with a severe clinical presentation. Coinheritance of alpha-thalassemia trait in the African haplotypes had an ameliorating effect on hemolytic episodes, but vaso-occlusive crises were more frequent.
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PMID:Genotype-phenotype correlation of sickle cell disease in the United Arab Emirates. 961 21

Sickle cell anemia is a monogenic hereditary disease characterized by a mutation in the beta globin gene. Five major haplotypes associated with the beta S mutation have been defined: Benin, Bantu, Senegalian, Camerounian, and Arabo-Indian. Previous studies in northern Tunisia showed that sickle cell anemia was of Benin origin in this region. Patients from the south of Tunisia, mainly from the Kebili region, were not previously concerned. In this study, we have determined the beta S haplotype and evaluated phenotypical expression of the disease in 14 patients from this latter region. The use of four restriction endonucleases having polymorphic sites in the beta globin gene showed that all patients had the Benin haplotype, confirming the Benin origin of sickle cell anemia in Tunisia. This haplotype is associated with an heterogeneous expression of fetal hemoglobin (HbF) with extremes varying from 2.4 to 16.3% and a mean expression rate of 8.16%, which is in accordance with literature data. In spite of the haplotype homogeneity in our patients, clinical heterogeneity was noted. A unique case of alpha-thalassemia could not explain this heterogeneity. In contrast, we found a certain correlation between fetal hemoglobin expression and clinical severity.
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PMID:[Hemoglobin beta S haplotype in the Kebili region (southern Tunisia)]. 961 41


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