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)

Delta-thalassemia is a complex group of inherited disorders of globin genes characterized by impaired synthesis of the delta-globin chain. The T-C substitution was detected at position -77 of the delta-globin gene isolated from three independent Japanese individuals who were homozygotes for delta-thalassemia. To elucidate the significance of the mutation in delta-globin gene expression, we investigated the genotype of three delta-thalassemia homozygotes and 58 normal individuals using dot blot hybridization of the polymerase chain reaction (PCR)-amplified DNA. The mutation was observed in six alleles of three homozygotes, while no mutation was detected in 116 alleles of normal individuals, thereby indicating the close association of this mutation with the thalassemia phenotype. Since the mutation (TTATCT-TCATCT) is located within the inverted binding motif of GATA-1 (T or A-G-A-T-A-G or A), an erythroid cell-specific transcription factor, we did gel retardation assays using nuclear extracts from the erythroid cells. We found that GATA-1 binds the oligonucleotide spanning positions -61 to -90, but does not bind to the oligonucleotide with the mutation at position -77. Competition gel retardation assays showed that GATA-1 binding can be competed out by the fragment with the GATA-1 motif, but not with the mutant oligonucleotide. Analysis of the transient expression of the CAT gene linked to the delta-globin gene promoter region demonstrated that the construct with the mutant promoter region was expressed about 20-fold less compared with the normal one. Thus, the mutation at position -77 impairs delta-globin gene expression by abolishing GATA-1 binding to the AGATAA sequence of the promoter region of the delta-globin gene. This provides a good example of involvement of tissue-specific transacting factors in the molecular pathogenesis of hereditary diseases.
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PMID:Delta-thalassemia caused by disruption of the site for an erythroid-specific transcription factor, GATA-1, in the delta-globin gene promoter. 151 47

During the course of a screening program for beta-thalassemia mutations among beta-thalassemia heterozygotes in Yugoslavia we observed a mutation (ATG----ACG) in the initiation codon of the beta-globin gene which has not been described before. The abnormality was initially detected through mapping of the beta-globin gene by Southern blot analysis using the restriction enzyme Nco I. The loss of the Nco I site resulted in the presence of an 8.3 kb band in addition to the normal 5.2 kb band. The mutation was identified by sequence analysis of amplified DNA and by dot-blot analysis of this DNA with a 32P-labeled oligonucleotide probe. An additional polymorphism (CAC----CAT) was present at codon 2 on the same chromosome; this mutation was detected by Orkin et al in 1982 (1). Hematological and in vitro chain synthesis data suggest that the beta-thalassemia is of the beta zero type.
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PMID:An initiation codon mutation as a cause of a beta-thalassemia. 227 40

Hb F-Malta-I [Ggamma117(19)His-->Arg, CAT-->CGT] is a stable and benign variant of Hb F found in 1.8% of Maltese newborn. We studied 120 Hb F-Malta-I heterozygotes and four Hb F-Malta-I homozygotes. The mean proportion of Ggamma-F-Malta-I in Hb F was 0.26 +/- 0.03 for the Hb F-Malta-I heterozygotes and 0.58 +/- 0.06 for the Hb F-Malta-I homozygotes. The Hb F-Malta-I allele was shown to occur on a background of the common Mediterranean haplotype Va [+ + - - - - - + + -]. Furthermore, the common Mediterranean haplotypes Va, IIIb [- + + + - + + + + -], I [+ + - - - - - + + +] and II [- + - + + - + + + +] accounted for most (66.2%) of the wild-type alleles among the tested Hb F-Malta-I heterozygotes. Different genotypes at the 5' epsilon HincII, Ggamma and Agamma HindIII, and 3'psibeta HincII sites (but not at the 5' Ggamma XmnI site) were found to be linked to significant variations in the proportion of Ggamma-F-Malta-I and Ggamma-globins in the Hb F of newborn Hb F-Malta-I heterozygotes. Moreover, the 5' Ggamma XmnI site was found to be associated with variations in Hb F and Ggamma-globin levels in a population of adult Maltese beta-thalassemia (thal) homozygotes. This implies that a determinant linked to the XmnI site which effects Ggamma-globin gene expression is active in anemic adults but not in normal infants.
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PMID:Developmental effect of the XmnI site on Ggamma-globin gene expression among newborn Hb F-Malta-I [Ggamma117(G19)His-->Arg, CAT-->CGT] heterozygotes and adult beta+ -Thalassemia homozygotes. 1736 7

This study was aimed to analyze the hematologic and molecular biologic characteristics of 14 Wenzhou patients with minor beta-thalassemia, to find out the mutation sites responsible for the disease by detecting sequences of PCR products and to analyze the single nucleotide polymorphism. The peripheral blood of patients was collected intravenously and was anticoagulated with EDTA-K(2); then the templates from blood samples were extracted, the related primers were designed for sequencing the products amplified by PCR; finally mutation sites resulting in beta-thalassemia were found through comparison and analysis of sequences. The results indicated that the C-->T heterozygous mutation occurred at the IVS-2 -654 site in 4 cases; the TTCT deficiency appeared at CD41/42 site in 1 case; in 2 sites existed single nucleotide polymorphisms occurring at the 59th site of exon 1 (T/C, CAT/CAC, His) and IVS-2 nt 665 (T/C). It is concluded that single nucleotide polymorphism of minor beta-thalassemia patients born in Wenzhou had specificity, this study found too kinds of gene mutations which are IVS-2 -654 C-->T heterozygous mutation and CD41/CD42 site-TTCT deficiency.
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PMID:[Analysis of single nucleotide polymorphism in the human beta-globin gene of patients with minor beta-thalassemia from Wenzhou]. 1892 3

Most of the endocrine complications in thalassaemia are attributable to iron overload which may be the result of economic circumstances (expense of the chelation therapy), late onset of chelation therapy or poor compliance with the iron chelation therapy. The major difficulties reported by hematologists or pediatric endocrinologists experienced in thalassaemias or thalassaemia syndromes in following growth disorders and endocrine complications were: lack of familiarity with medical treatment of endocrine complications (40%), interpretation of endocrine tests (30%), costs (65%), absence of paediatric endocrinologist for consultation on growth disorders and endocrine complications (27%), facilities (27%), other (e.g. lack of collaboration and on-time consultation between thalassaemic Centers supervised by hematologists and endocrinologists) (17%). Because any progress we make in research into growth disorders and endocrine complications in thalassaemia should be passed on to all those suffering from it, guaranteeing them the same therapeutic benefits and the same quality of life, on the 8th of May, 2009 in Ferrara (Italy), the International Network on Endocrine Complications in Thalassemia (I-CET) was founded. The I-CET group is planning to conduct, in Ferrara in May 2012, a workshop, "MRI and Endocrine Complications in Thalassaemia", and in Doha (Qatar) in September 2012, a 3-day intensive course entitled, "Growth disorders and Endocrine Complications in Thalassaemia", to provide interested pediatricians, physicians and hematologists from all over the world with an in-depth approach to the diagnosis and management of growth and endocrine disorders in thalassaemic patients.
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PMID:International network on endocrine complications in thalassaemia (I-CET): an opportunity to grow. 2266 32

The current management of thalassemia includes regular transfusion programs and chelation therapy. It is important that physicians be aware that endocrine abnormalities frequently develop mainly in those patients with significant iron overload due to poor compliance to treatment, particularly after the age of 10 years. Since the quality of life of thalassemia patients is a fundamental aim, it is vital to monitor carefully their growth and pubertal development in order to detect abnormalities and to initiate appropriate and early treatment. Abnormalities should be identified and treatment initiated in consultation with a pediatric or an adult endocrinologist and managed accordingly. Appropriate management shall put in consideration many factors such as age, severity of iron overload, presence of chronic liver disease, thrombophilia status, and the presence of psychological problems. All these issues must be discussed by the physician in charge of the patient's care, the endocrinologist and the patient himself. Because any progress in research in the field of early diagnosis and management of growth disorders and endocrine complications in thalassemia should be passed on to and applied adequately to all those suffering from the disease, on the 8 May 2009 in Ferrara, the International Network on Endocrine Complications in Thalassemia (I-CET) was founded in order to transmit the latest information on these disorders to the treating physicians. The I-CET position statement outlined in this document applies to patients with transfusion-dependent thalassemia major to help physicians to anticipate, diagnose, and manage these complications properly.
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PMID:Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I-CET) position statement and guidelines. 2377 48

Oxidative stress would play a role in the pathophysiology of sickle cell anemia (SCA). We tested the impact of common SCA genetic modifiers (alpha-thalassemia, G6PD deficiency, HbF quantitative trait loci; QTL) and pro/antioxidant genes polymorphisms (SOD2 rs4880, XO rs207454, MPO rs233322) on oxidative stress biomarkers (AOPP, MDA, MPO, XO, MnSOD, CAT, GPx) and clinical severity in 301 Senegalese SCA hydroxyurea-free children at steady-state (median age 9.1 years, sex ratio H/F = 1.3). Plasma oxidative stress biomarkers were compared with those of a control group (AA). CAT activity, AOPP, and MDA levels were higher in SCA than in AA individuals while XO, GPX, and MnSOD activities were lower. The presence of alpha-thalassemia decreased MDA level and MPO activity but no effect of the HbF QTL or G6PD deficiency was observed. SCA children who experienced their first hospitalized complication before 3 years old had higher MnSOD and CAT activities than the other children while those with no hospitalized VOC in the previous 2 years presented higher GPX activity. Age of the first hospitalized complication and AOPP levels were affected by the MPO rs2333227 SNP. Our results suggest that alpha-thalassemia modulates oxidative stress in SCA, presumably because of a reduction in the MPO activity.
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PMID:Influence of Oxidative Stress Biomarkers and Genetic Polymorphisms on the Clinical Severity of Hydroxyurea-Free Senegalese Children with Sickle Cell Anemia. 3293 82