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)

Chronic hemolysis, with consequent hyperbilirubinemia, predisposes SS patients to pigment gallstones. The other factors which influence the development of stones in these patients have not been identified. We have carried out a combined prospective and retrospective study of SS patients in Kuwait and specifically investigated the influence of coexistent alpha-thal trait on the prevalence of gallstones. A total of 45 patients (30 males, 15 females) with ages ranging from 1 to 16 years (mean 7.2 +/- 3.1) were studied. Most were either homozygotes for the Saudi Arabia/India haplotype (86.7%) or compound heterozygotes for this and the Benin haplotype (11.1%). They were screened for gallstones with ultrasonography. alpha-Globin genotypes were determined using a combination of PCR and allele-specific oligonucleotide hybridization techniques to identify the common alpha-thalassemia alleles in this population. Gallstones were detected in 7 (15.6%) patients (4 males, 3 females), whose mean age (10.5 +/- 5.5 years) was significantly higher than that (6.8 +/- 3.2 years) of those without stones (p < 0.01). The mean total Hb of the former (8.4 +/- 0.8 g/dl) was also significantly (p < 0.05) lower than in the latter (9.5 +/- 1.3 g/dl), while the difference in mean Hb F levels was not significant. None of the 4 alpha-thal homozygotes had gallstones while 2 of 13 heterozygotes and 5 of the 23 patients without coexistent alpha-thal had. The differences in these proportions are statistically significant (chi2 = 20.4, p < 0. 001). It therefore appears that coexistent alpha-thal decreases the chance of developing gallstones in Arab SS patients. This may be related to less hemolysis in such patients as shown by their higher mean Hb level.
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PMID:Influence of alpha-thalassemia on cholelithiasis in SS patients with elevated Hb F. 985 92

Twenty-five individuals were studied from four unrelated Mexican Mestizo families with Hb D-Los Angeles. We observed five compound heterozygotes: four for Hb S and Hb D, and one for Hb D and beta-thalassemia (beta(0) 39 nonsense mutation); 16 heterozygotes: four for Hb S, seven for Hb D, and five for beta-thalassemia, while the remaining four were normal. The four Hb S/Hb D patients had severe hemolytic anemia, while in the Hb D/beta-thalassemia patient, the anemia was similar to that of a beta-thalassemia heterozygote; therefore, Hb D is clinically harmful when it is associated with Hb S. The beta(S) chromosomes were associated with the Benin haplotype in two families and Bantu in one family, while the beta(D) and beta(0) 39 mutations were associated with haplotype 1 [+ - - - - + +]. The Bantu and Benin haplotypes have been found with high frequency in Hb S individuals from the East Coast and Northwestern Mexico. The beta(D) chromosomes from Italy were also shown to be associated with haplotype 1, the most frequently observed haplotype in the world; there are no haplotype studies on beta(D) chromosomes from India or China where Hb D-Los Angeles is most common. Thus, the true origin of this mutation observed in these Mestizo families remains to be elucidated.
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PMID:Hb D-Los Angeles associated with Hb S or beta-thalassemia in four Mexican Mestizo families. 1049 Jan 35

We analyzed beta-globin gene cluster haplotypes and deletional alpha+-thalassemia (-alpha3.7kb) in 54 Babinga pygmy subjects from Congo-Brazzaville. The beta(S)-globin gene frequency was 0.065 and that of the deletional alpha-globin gene (-alpha3.7kb) was 0.29. Eighty-five percent of the beta(S) chromosomes and 13% of the beta(A) chromosomes were associated with the Bantu haplotype, 10% of beta(A) chromosomes with the Senegal haplotype, and the remaining beta chromosomes with atypical haplotypes. None of the chromosomes were of the Benin haplotype. These results are clearly of anthropological and evolutionary interest. They also support earlier observations that alpha+-thalassemia is prevalent at a high frequency in African populations.
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PMID:Beta-globin gene haplotypes and alpha-thalassemia analysis in Babinga pygmies from Congo-Brazzaville. 1080 67

Sickle cell anemia and alpha-thalassemia have a heterogeneous distribution in Venezuela with a high frequency in the coastal area (sea level) and few cases in the mountains. Most of our population is an ethnic admixture of Europeans (Spaniards colonists), Africans (slaves), and Amerindians. The purpose of our study was to determine the origin of the beta(s) globin haplotype, age and survival dependency, and the admixture among the different African groups in our population. The alpha(3.7) globin gene deletion status was also studied and found in a very high frequency. DNA from peripheral blood of 191 non-related patients (81 with HbS homozygous and 15 patients compound heterozygous for HbS, HbC, HbD with beta-thalassemia, and 95 with sickle cell trait) were studied. The beta(s) chromosome was linked 51% to the Benin Haplotype, 29.5% with the CAR, 12.5% to the Senegal, and 2.5% to the Cameroon. We did not find any significant difference between the haplotype distribution among adults and children and among sickle cell patients and traits. Only 8.6% of the patients have homozygosity for the Benin haplotype. These results show a very high frequency of admixture in our African origin population.
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PMID:Determination of beta-globin gene cluster haplotypes and prevalence of alpha-thalassemia in sickle cell anemia patients in Venezuela. 1081 85

We have studied a four-generation (23 subjects) African-American family with beta(o) thalassemia and high fetal hemoglobin (HbF) levels. The beta(o) thalassemia in this family is due to the splicing site mutation, beta IVS2+1G-->A, that leads to aberrant mRNA processing and the absence of beta globin. Two members of this family are homozygous for beta(o) thalassemia and are non-anemic. All family members who are heterozygous for the beta IVS2+1G-->A mutation have elevated HbF, with the exception of two individuals who also have severe alpha-globin chain deficiency. We excluded linkage with the hereditary persistence of fetal hemoglobin loci on chromosomes 6 and X. We also excluded the presence of all previously described determinants in the beta globin gene cluster associated with elevated HbF production. One thalassemia allele is in the Cameroon-like (HS2)/Benin-like beta globin gene cluster haplotype, and the other is in the Senegal-like (HS2)/Benin-like beta globin gene cluster haplotype. We speculate that in the homozygotes, those erythroid cells that express low to absent levels of gamma globin are selectively destroyed. In contrast, in the heterozygotes, the presence of the normal beta globin allele would ameliorate the globin chain imbalance and thus allow survival of erythroid cells that express the abnormal transcript, leading to a typical beta(o) thalassemia phenotype. Thus, the heterocellular gamma globin expression together with in vivo preferential survival of HbF-containing erythroid cells ameliorates Cooley's anemia in the beta(o) thalassemia homozygotes. It remains to be determined what sequences linked to each thalassemia allele and what trans-acting factors contribute to high HbF levels.
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PMID:Non-anemic homozygous beta(o) thalassemia in an African-American family: association of high fetal hemoglobin levels with beta thalassemia alleles. 1155 36

Sickle cell anemia in Iran is accompanied by a high level of HbF and mild clinical presentation. Here we report haplotypes of the beta gene cluster found in 81 randomly selected sickle cell patients, including 47 sickle cell anemia (SS), 17 sickle cell trait (AS), and 17 sickle/thalassemia (S/thal) from southwest Iran. We found all five common typical haplotypes as well as five atypical haplotypes in our patients. Except for four patients with homozygous Benin haplotype, none of the other African typical haplotypes were found in a homozygous state. Arab-Indian was found to be the most prevalent haplotype in the study population. This haplotype accounted for 51.1% as the homozygous form in SS patients, where 69.1% of chromosomes in these patients had the Arab-Indian haplotype. Bantu A2 was the second most prevalent haplotype among all patients. The mean %HbF in SS patients was 27.83 and in the homozygous Arab-Indian haplotype it was still higher (30.40%), while in AS patients the %HbF was only 1.20. The high %Ggamma chain (71.81) in the Arab-Indian homozygous haplotype was concomitant with the presence of an Xmn I site in both chromosomes. The presence of the Arab-Indian haplotype as the predominant haplotype might be suggestive of a gene flow to/from Saudi Arabia or India. More haplotype investigations of a normal population can clarify the high incidence of Bantu A2 haplotype in our population.
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PMID:Beta-globin gene cluster haplotypes in sickle cell patients from southwest Iran. 1458 41

The beta(S)-globin haplotypes were studied in 78 sickle cell Brazilian patients from Bahia, Northeast Brazil, that has a large population of African origin. Hemoglobin (Hb) profiles were developed by high-performance liquid chromatography (HPLC), and beta(S)-globin gene haplotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques. We identified 44 (55.0%) patients with the CAR/Ben (Central African Republic/Benin) genotype, 16 (20.0%) Ben/Ben, 13 (16.2%) CAR/CAR and seven (8.8%) with other genotypes. Analyses of the phenotypes showed clinical differences related only to Hb F levels and blood transfusion therapy; the presence of -alpha(-3.7)-thalassemia (thal) demonstrated statistical significance when associated with hematocrit (p=0.044), MCV (p=0.0007), MCH (p=0.012) and spleen sequestration events. The haplotype diversity found in the present study can be justified by information about the origin of the slave traffic period in Bahia during the 19th century. The specific characteristics described among the Bahian sickle cell patients could be confirmed by increasing the number of patients with specific genotypes and further studies of genetic markers.
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PMID:The beta-globin gene cluster haplotypes in sickle cell anemia patients from Northeast Brazil: a clinical and molecular view. 1548 97

The hemoglobinopathies affect the blood red cells and are the most common monogenic diseases worldwide. The high frequency and clinical severity of the hemoglobinopathies, make them a major public health problem. We report here an updated review on epidemiologic and molecular data of the hemoglobinopathies in Tunisia. From 1980 to 2005, a screening of hemoglobinopathies was performed on a total of 44299 individuals according to 2 kinds of work: a systematic screening on several populations (24240) from different regions of the country and a cohort of individuals referred to our laboratory for hemoglobinopathies suspicion (20059). Blood was collected in EDTA tubes from the studied individuals to determine the hematological parameters, the hemoglobin electrophoretic data and the iron status. DNA analysis was performed by the usual PCR based-procedures for the molecular defects identification. Systematic surveys allowed us to show an average prevalence of hemoglobinopathy carriers of 4.48% reaching 12.50% in some focus regions. The average frequency of B-thal trait is of 2.21% and that of sickle cell trait is of 1.89%. Hemoglobin screening on newborns has shown a frequency of alpha-thal trait of 5.48%. Oriented studies from our hospital experience allowed us to list more than 2394 major forms. Molecular analysis on beta-thalassemia patients allowed to identify 21 different alleles. The two most frequent mutations (cd39 C-->T and IVS1-110 G-->A) accounted for 70% of the total encountered beta-thal mutations. Among the other mutations, three were described for the first time in the world on Tunisian families. The sickle cell disease is associated with the Benin haplotype in 95% of the studied cases. Concerning alpha-thal mutation, the - alpha37 deletion was the most common. We also note the identification of several rare Hemoglobin variants as well as diverse associated forms of anomalies. Knowledge of epidemiological and molecular data of hemoglobinopathies is fundamental to understand the mechanisms of disease expression and the genotype / phenotype correlations. Furthermore, the distribution of the hemoglobinopathies in the regions allows to orientate efficiently the planning tasks regarding control and prevention of these hereditary diseases.
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PMID:[Hemoglobinopathies in Tunisia. An updated review of the epidemiologic and molecular data]. 1729 92

Various factors have been described as phenotypic modulators of sickle cell disease, such as levels of fetal hemoglobin (Hb F), presence of alpha-thalassemia (thal), and haplotypes of the beta-globin genes. In order to characterize and determine the frequency of the betaS and betaC mutations and the prevalence of -alpha3.7-thal, 74 patients with sickle cell disease detected during neonatal screening in the State of Pernambuco, Brazil, were studied. The haplotypes of the beta gene and -alpha3.7-thal were determined using polymerase chain reaction (PCR), and specific restriction endonucleases were used to establish the polymorphic sites of the haplotypes. The results showed the high frequency of the Central African Republic (CAR) or Bantu haplotype in the State of Pernambuco, Brazil. The low frequency of the Benin haplotype recorded in this study, in comparison with other states in northeast Brazil, suggests the diversity of origins of Afro-Brazilians in this region.
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PMID:Molecular variations linked to the grouping of beta- and alpha-globin genes in neonatal patients with sickle cell disease in the State of Pernambuco, Brazil. 1736 8

To determine the origin of sickle cell mutation in different ethnic groups living in southern Iran, we studied the haplotype background of the betaS and betaA genes in subjects from the provinces of Fars, Khuzestan, Bushehr, Hormozgan, and Kerman and from the islands of Khark and Qeshm. beta-globin gene cluster haplotypes were determined using the PCR-RFLP technique. Detection of -alpha 3.7 deletion and beta-thalassemia mutations were defined by PCR and reverse dot blot techniques, respectively. The framework of the beta-globin gene was determined using denaturing gradient gel electrophoresis. We found that the betaS mutation in southern Iran is associated with multiple mutational events. Most of the patients were from two ethnic groups: Farsi speakers (presumably Persian in origin) from Fars province and patients of Arab origin from Khuzestan province. In both ethnic groups the Arab-Indian haplotype was the most prevalent. The frequencies of the Arab-Indian and African haplotypes in sickle cell anemia patients from the provinces of Fars and Khuzestan were similar. Among betaA chromosomes the Bantu A2 haplotype was the most prevalent. The decrease in alpha-globin production in SS patients and AS individuals appeared to be related to the reduction in mean cell volume and mean cell hemoglobin. The Arab-Indian haplotype gene flow into this region of Iran can be traced to the Sassanian Empire. It is likely that the influx of betaS genes linked to the Benin and Bantu haplotypes, of African origin, must have occurred during the Arab slave trade.
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PMID:Implications of the genetic epidemiology of globin haplotypes linked to the sickle cell gene in southern Iran. 1756 50


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