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

Thalassemias and hemoglobinopathies are very common among Southeast Asian populations, particularly in Thailand, where it is estimated that nearly 30% of the population carries at least one such disorder. Moreover, the heterogeneity of different mutant alpha- and beta-globin alleles contributes to the complexity in diagnosis and proper management, as more than 60 thalassemia syndromes and hemoglobinopathies have been described. Herein we report a further case of Hb G-Coushatta [beta22(B4)Glu-->Ala (GAA-->GCA)] (also known as G-Saskatoon, G-Hsin Chu and G-Taegu) in a Thai family in which the mother was found to have an unusual hemoglobin (Hb) anomaly in combination with Hb E [beta26(B8)Glu-->Lys, GAG-->AAG]. We applied our recently described polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique to scan the beta-globin genes and found an aberrant pattern in exon 1. The molecular analysis by direct genomic sequencing successfully identified the nucleotide mutation (codon 22, GAA-->GCA), and a novel amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) for this variant is described.
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PMID:Further identification of Hb G-Coushatta [beta22(B4)Glu-->Ala (GAA-->GCA)] in Thailand by the polymerase chain reaction-single-strand conformation polymorphism technique and by amplification refractory mutation system-polymerase chain reaction. 1736 10

Hemoglobin E (beta26Glu --> Lys) is the most common hemoglobin (Hb) variant in Southeast Asia and the second most prevalent worldwide. However in India, it is prevalent in Bengal and the north-eastern region, but relatively rare in the rest of the country. Identification of this Hb variant is important, because the doubly heterozygous state for HbE and beta-thalassemia is characterized clinically by thalassemia major, a situation different from other compound heterozygous states for structural beta-chain variants and beta-thalassemia. Thus, the affected individual may be symptomatic and transfusion dependent at an early age. This paper reports four cases with Hb E trait, three cases with hemoglobin E disease and another four cases with Ebeta-thalassemia. Laboratory investigations are based on RBC indices and high performance liquid chromatography (HPLC). A negative correlation has been found to exist between levels of HbA(2) and RBC indices including the MCV and MCH. A similar correlation has been seen between levels of HbF with Hb, RBC count, and MCV. The main aim is to increase the awareness of this relatively rare disorder, so that it can be included in the differential diagnosis of patients presenting clinically like thalassemia intermedia or thalassemia major. This awareness may also help in prenatal diagnosis, genetic counseling and clinical management. The clinical, hematological and laboratory features of this disorder are also discussed.
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PMID:Hemoglobin E disease in North Indian population: a report of 11 cases. 1765 63

Here, we report a rare coincidence of heterozygous hemoglobinopathy (Hb) Stanleyville II and severe pernicious anemia due to autoimmune gastritis. Hb Stanleyville II is characterized by a single base exchange (AAC-->AAA) resulting in a substitution Asn --> Lys at position 78 of hemoglobin alpha2-chain. Under normal conditions this hemoglobinopathy does not cause any symptoms even if present as homozygous variant. However, in our case diagnosis of pernicious anemia was hampered by the absence of typical erythrocytic macrocytosis and hyperchromasia. In addition, interpretation of bone marrow smears was difficult as characteristic findings for pernicious anemia were little pronounced. All known reasons for the absence of typical cytomorphologic signs in pernicious anemia as underlying iron deficiency and thalassemia could be excluded.
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PMID:Cytomorphologic signs of severe pernicious anemia obscured in a patient with heterozygous hemoglobin Stanleyville II. 1768 Aug 15

We studied 325 thalassemia intermedia patients from Iran, India, Pakistan, Thailand, Mauritius and Cyprus to examine factors which influence the phenotype. The beta-thalassemia (thal) mutations were determined for 219 beta-thal/beta-thal and 106 beta-thal/Hb E [beta26(B8)Glu-->Lys, GAG-->AAG] thalassemia intermedia patients. Thirty-one different mutations were identified, and their combination gave rise to more than 44 different genotypes, of which 14 (31.8%) had the beta(0)/beta(0), 21 (47.7%) the beta(0)/beta(+) and nine (20.5%) the beta(+)/beta(+) types. Thus, the beta(+)-thal mutations were present in 68.2% of patients. alpha-Thalassemia mutations were present in frequencies higher than in the general population of all ethnic groups studied, as 45% of the patients carried alpha-thal mutations. Correlation of alpha-thal mutations with beta-globin mutations showed that the alpha-thal mutations were mainly co-inherited with the beta(+)-thal mutations. The XmnI (G)gamma polymorphic site at -158 (C-->T) was positive (T) in nine (8.8%) of 102 patients of the beta(+)/beta(+) genotype, and the percentage of both XmnI (G)gamma polymorphism [+/-] (T/C) and [+/+] (T/T) genotypes increased to 42.9 and 87.3, respectively, in the beta(0)/beta(+) and beta(0)/beta(0) patients. This polymorphism was found in the majority of beta(+)-thal/Hb E compound heterozygote patients (88.6%), and beta(0)-thal/Hb E patients (84.8%), suggesting that it could be linked to the Hb E chromosome. Therefore, the XmnI (G)gamma polymorphism at -158 (C-->T) was associated with beta(0)-thal mutations as well as the Hb E chromosome. The present study demonstrates that in cases of thalassemia intermedia with beta(+) mutations, the common ameliorating factor is the presence of alpha-thal mutations, while in cases with beta(0) mutations, the common ameliorating factor is the presence of the XmnI (G)gamma polymorphism at -158 (C-->T).
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PMID:Multicenter study of the molecular basis of thalassemia intermedia in different ethnic populations. 1799 78

Histone covalent modifications regulate many, if not all, DNA-templated processes, including gene expression and DNA damage response. The biological consequences of histone modifications are mediated partially by evolutionarily conserved "reader/effector" modules that bind to histone marks in a modification- and context-specific fashion and subsequently enact chromatin changes or recruit other proteins to do so. Recently, the Plant Homeodomain (PHD) finger has emerged as a class of specialized "reader" modules that, in some instances, recognize the methylation status of histone lysine residues, such as histone H3 lysine 4 (H3K4). While mutations in catalytic enzymes that mediate the addition or removal of histone modifications (i.e., "writers" and "erasers") are already known to be involved in various human diseases, mutations in the modification-specific "reader" proteins are only beginning to be recognized as contributing to human diseases. For instance, point mutations, deletions or chromosomal translocations that target PHD fingers encoded by many genes (such as recombination activating gene 2 (RAG2), Inhibitor of Growth (ING), nuclear receptor-binding SET domain-containing 1 (NSD1) and Alpha Thalassaemia and Mental Retardation Syndrome, X-linked (ATRX)) have been associated with a wide range of human pathologies including immunological disorders, cancers, and neurological diseases. In this review, we will discuss the structural features of PHD fingers as well as the diseases for which direct mutation or dysregulation of the PHD finger has been reported. We propose that misinterpretation of the epigenetic marks may serve as a general mechanism for human diseases of this category. Determining the regulatory roles of histone covalent modifications in the context of human disease will allow for a more thorough understanding of normal and pathological development, and may provide innovative therapeutic strategies wherein "chromatin readers" stand as potential drug targets.
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PMID:PHD fingers in human diseases: disorders arising from misinterpreting epigenetic marks. 1868 56

Peptide nucleic acid (PNA) is highly stable and binds to complementary RNA and DNA with high affinity, but it resists cellular uptake, thereby limiting its bioavailability. We investigated whether protectiveantigen (PA, a non-toxic component of anthrax toxin) could transport antisense PNA oligomers into reporter cells that contain luciferase transgenes with mutant beta-globin IVS2 intronic inserts, which permit aberrant pre-mRNA splicing and impair luciferase expression. PNA oligomers antisense to mutant splice sites in these IVS2 inserts induced luciferase expression when effectively delivered into the cells. PNA 18-mers with C-terminal poly-lysine tails [PNA(Lys)(8)] demonstrated modest sequence-specific antisense activity by themselves at micromolar concentrations in luc-IVS2 reporter cell cultures. However, this activity was greatly amplified by PA. Antisense PNA(Lys)(8) with but not without PA also corrected the IVS2-654 beta-globin splice defect in cultured erythroid precursor cells from a patient with beta-thalassemia [genotype, IVS2-654(beta(0)/beta(E))], providing further evidence that anthrax PA can effectively transport antisense PNA oligomers into cells.
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PMID:Effective delivery of antisense peptide nucleic acid oligomers into cells by anthrax protective antigen. 1877 71

The distribution of hemoglobin E (alpha2beta2 26Glu (R)Lys ) is mostly restricted to Northeastern India. While evaluating the patients of jaundice, we came across two cases of hemoglobin E (Hb E) disorders. The first case is in a 22-year-old Bengali male and the second case of Hb E/beta thalassemia in a 5-year-old Hindu boy. The family study revealed Hb E trait in both the parents of Case 1, whereas in Case 2, the father was found to have Hb E trait and the mother had beta -thalassemia minor, thus confirming the diagnosis. Herein, we present the laboratory diagnosis and comparative data of the spectrum of Hb E disorders (i.e., heterozygous Hb E trait, homozygous Hb E disease and compound heterozygous Hb E/beta -thalassemia) that was found in our index cases and their parents.
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PMID:Hemoglobin E disorders in Eastern Uttar Pradesh. 1913 1

beta-Globin haplotypes have been used to investigate the origin and spread of beta-globin mutations such as Hb S [beta 6(A3)Glu-->Val, GAG>GTG], Hb E [beta 26(B8)Glu-->Lys, GAG>AAG], and beta-thalassemia (beta-thal). Molecular analyses revealed the presence of 17 beta-thal mutations in the Mexican population; the most frequent of these are the nonsense codon 39 (C>T), IVS-I-1 (G>A), IVS-I-110 (G>A), and -28 (A>C). To improve our knowledge about their origin, we analyzed the 5' haplotypes by restriction fragment length polymorphism. The codon 39 mutation (n = 17) was observed with five 5' haplotypes: 1 (59%), 2 (23%), and 4, 6, and 9 (6% each). The IVS-I-1 mutation (n = 15) was found with five 5' haplotypes: 1 (73.6%), 2, 3, 5, and 11 (6.6% each), whereas the IVS-I-110 (n = 9) and -28 mutations (n = 1) were only associated with haplotype 1. In the population studied, the codon 39 and IVS-I-1 mutations show a multicentric origin, whereas the IVS-I-110 and -28 mutations have an apparent single origin. Further investigation is required for the analysis of the polymorphisms surrounding the beta-globin gene.
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PMID:Diversity of the 5' beta-globin haplotype of four beta-thalassemia mutations in the Mexican population. 1920 76

Conventional diagnosis of hereditary red blood cell (RBC) membrane disorders, in particular hereditary spherocytosis (HS), is labor intensive, time consuming and requires at least 2 ml of blood, which might be impractical in neonatal period. We evaluated the use of eosin-5-maleimide (EMA), a dye that reacts covalently with lysine-430 on the first extracellular loop of band 3 protein, for rapid screening test of patients with HS and Southeast Asian Ovalocytosis (SAO). Fresh RBCs from 142 healthy controls, 50 HS, 17 SAO, 29 hereditary elliptocytosis, 5 autoimmune hemolytic anemia, 66 patients with beta-thalassemia/HbE, 31 cases with alpha-thalassemia (HbH disease) and 4 cases with pyruvate kinase deficiency were stained with EMA, and analyzed for their mean channel fluorescence (MCF) using a flow cytometer. RBCs from patients with HS and SAO expressed a greater degree of reduction in MCF compared to those from normal controls and other hemolytic diseases. These findings showed that the fluorescence flow cytometric-based method is a simple, sensitive and reliable diagnostic test for RBC membrane disorders using a small volume of blood, and results could be obtained within 2 hours. Such method could serve as a first line screening for the diagnosis of HS and SAO in routine hematology before further specific membrane protein electrophoresis and molecular diagnosis are employed.
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PMID:Rapid flow cytometric test using eosin-5-maleimide for diagnosis of red blood cell membrane disorders. 1984 45

HbE [beta 26 Glu-Lys] is the second most common abnormal Hb in humans. HbE when associated with beta thalassemia (HbE/beta thalassemia) in compound heterozygous state results in a clinically severe condition. HbE/beta thalassemia has a very variable clinical phenotype. One of the possible explanations for the observed variable clinical severity is variation of alpha gene number. The main aims of this study were to determine the frequency of alpha deletion/mutations and triplication in HbE/beta thalassemia patients and to study the effect of alpha gene numbers on the phenotype of these patients. 240 HbE/beta thalassemia patients who attended the Hematology Outpatient Department of the Institute were studied. Patients were divided into three groups mild (score=0-3.5), moderate (score=4-7) and severe (score=7.5-10). alpha deletion was found in 22 (7.5%), out of these 22 patients 16 (11 alphaalpha/-alpha(3.7), 4-alpha(3.7)/-alpha(3.7) & 1 alphaalpha/--(SA)) were from Gp I and 6 (alphaalpha/-alpha(3.7)) were from Gp II. alpha triplication was found in 7 (2.9%) and out of these 7 patients 5 were (alphaalpha/alphaalphaalpha(anti-3.7)) from Gp III and 2 were (alphaalpha/alphaalphaalpha(anti-3.7)) from Gp II. The most common interaction was found to be HbE/beta thalassemia and deletional alpha(+)-thalassemia (alphaalpha/-alpha(3.7)) followed by others. alpha deletions and point mutations genotype were mostly observed in the individuals from Gp I while alpha triplication was most frequent in Gp III individuals. Interaction of HbE/beta thal with alpha-thalassemia is common in the Indian population. Patients inheriting alpha deletions and point mutations behaved mildly with some exceptions, while patients with alpha triplication had a severe phenotype requiring frequent transfusions.
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PMID:Alpha globin gene numbers: an important modifier of HbE/beta thalassemia. 1984 87


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