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)

A novel beta-chain, beta 126(H4)Val----Gly, electrophoretically silent, was detected by reverse-phase high performance liquid chromatography in three unrelated families from Naples (Southern Italy) and accounted for about 30% of the total beta-chains. The amino acid substitution was detected by HPLC fingerprint. The eight heterozygous patients showed hematologic and biosynthetic alterations of mild beta-thalassemia type. The hemoglobin variant showed abnormal stability features. It was unstable in the heat stability and isopropanol precipitation tests, but did not cause a hemolytic syndrome in vivo and was stable in a time-course experiment of biosynthesis in vitro. DNA polymerase chain reaction direct sequencing of the mutated gene from 135 nt upstream of the cap site to 106 nt downstream of the polyadenylation site showed only the beta 126 GTG----GGG mutation, which was confirmed in the other patients by allele-specific oligonucleotide hybridization. The mutation was found to be associated with a type II beta-globin framework and restriction fragment length polymorphism haplotype V. The novel variant was named hemoglobin Neapolis.
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PMID:Hemoglobin Neapolis, beta 126(H4)Val----Gly: a novel beta-chain variant associated with a mild beta-thalassemia phenotype and displaying anomalous stability features. 195 92

We have developed methodology that allows comparison of the mean corpuscular hemoglobin (MCH) of fetal hemoglobin (HbF)-containing red cells (F cells) with the MCH of non-F cells from the same individual. To do this, suspensions of peripheral blood erythrocytes and their internal contents are fixed with an imidodiester, dimethyl-3,3'-dithiobispropionimidate dihydrochloride (DTBP). Thereafter fixed cells are made permeable to antisera by treatment with Triton X-100 and isopropanol, reacted with a mouse monoclonal antibody (MoAb) against HbF, and then with fluorescein-conjugated antimouse IgG. No appreciable hemoglobin is lost during such manipulation. Red cells from a diversity of subjects were thus treated and examined microscopically, first by transmitted light and then by epifluorescence. A direct correlation between Coulter-derived MCH and mean absorbance of 415 nm transmitted light was found for 100 unfixed (r = 0.96) and for 100 antibody-treated fixed-permeabilized red cells (r = 0.99) among individuals selected so as to provide a range of Coulter MCH values between 20 and 35. Comparisons of microscopically derived MCH of F cells and non-F cells were statistically nondistinguishable (P greater than 0.05) in all subjects. Such comparisons included normal individuals (less than 1% F cells), SS patients (7% to 48% F cells), subjects with congenital anemia (22% to 65% F cells), individuals with heterocellular hereditary persistence of HbF (HPFH) (12% to 21% F cells), and heterozygotes for beta + thalassemia (11% to 31% F cells). We conclude that gamma- and beta-globin production within F cells is regulated in a reciprocal fashion both among normal individuals and among individuals with elevated HbF production.
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PMID:Fetal hemoglobin-containing cells have the same mean corpuscular hemoglobin as cells without fetal hemoglobin: a reciprocal relationship between gamma- and beta-globin gene expression in normal subjects and in those with high fetal hemoglobin production. 243 42

A new hematologic syndrome with phenotypic features of mild Hb H disease was identified in three children from two unrelated black American families. Erythrocytes from each of these children contained Hb H (beta 4) and Hb Barts (gamma 4), as well as a slowly migrating hemoglobin fraction that made up 7-10% of the total hemoglobin. The parents of the affected children all showed mild thalassemia-like changes, with one of the parents in each family also expressing the variant hemoglobin; in the latter individuals the mutant alpha-chains made up less than 2% of the total, and were present mainly or exclusively in combination with delta-chains in the form of a slowly migrating Hb A2. Purified Hb Evanston showed an increased oxygen affinity, but its Bohr effect, cooperativity, and 2,3-diphosphoglycerate effect were normal. The mutant hemoglobin appeared to have normal stability to heat and to isopropanol, and the stability of its alpha-chain in an extended time course synthesis study also appeared to be similar to that of alpha A. However, the results from short-term globin synthesis studies, and from mRNA translation in vitro, suggest that the two types of alpha-chains were synthesized at relatively equal rates, with a major fraction of the newly synthesized variant alpha-chains undergoing rapid catabolism. The hematologic data taken in combination with DNA hybridization and globin synthesis findings indicate that the proposita in each of these families has the genotype--, alpha A/--, alpha Ev. These observations suggest that two separate mechanisms are contributing to the alpha-thalassemia-like expression of Hb Evanston : the newly synthesized alpha EV-chains are unstable and are subject to early proteolytic destruction; and the mutant alpha-allele is linked to an alpha-globin gene deletion.
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PMID:Hemoglobin Evanston (alpha 14 Trp----Arg). An unstable alpha-chain variant expressed as alpha-thalassemia. 672 58

Blood samples from 1,000 individuals seen at the Instituto Mexicano del Seguro Social in northwestern Mexico were assayed by multiple systems (acid, alkaline and neutral electrophoresis, heat, freeze and isopropanol stability and erythrocytic morphology under hypoxia) to detect hemoglobin (Hb) abnormalities. Two beta-thalassemia heterozygotes (0.2 per cent), five Hb S heterozygotes (0.5 per cent) and three probable new Hb variants (0.3 per cent) were identified. These preliminary results give a general idea of the gene frequencies in this population, but do not yet permit the evaluation of the relative advantage of multiple methodology for the detection of abnormal Hbs.
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PMID:Detection of hemoglobin alterations in a sample population in northwest Mexico. Preliminary report. 721 9

We describe a rapid, automated method for direct detection of known single-base changes in genomic DNA. Fluorescence-based DNA minisequence analysis is employed in a template-dependent reaction which involves a single nucleotide extension of an oligonucleotide primer by the correct fluorescently-tagged dideoxynucleotide chain terminator. Detection following electrophoresis on denaturing acrylamide gels is facilitated by alkaline phosphatase treatment of reaction products after extension followed by isopropanol precipitation of the dye-tagged, single-base-extended primer to remove unincorporated deoxynucleotides. Fluorescence analysis of the incorporated dye tag reveals the identity of the template nucleotide immediately 3' to the primer site. This technique does not require radioactivity or biotinylated PCR product, relies on the incorporation of a single dideoxynucleotide terminator to extend the primer by one nucleotide and takes advantage of the sensitivity of fluorescent terminators developed for automated DNA sequence analysis. As a demonstration, we have applied the assay to human genomic DNA for detection of the sickle mutation in the beta-globin gene, and have also examined feasibility for simultaneous delineation using a multiplex-like strategy in a single gel-lane of some of the most common beta-thalassemia mutations in the Mediterranean basin.
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PMID:Fluorescence-based DNA minisequence analysis for detection of known single-base changes in genomic DNA. 747 10

A patient originating from Iraq was referred to our laboratory upon suspicion of a hemoglobinopathy. Routine hematological tests revealed a microcytic and slightly anemic phenotype with an elevated HbA2 suggestive of beta-thalassemia. Samples were obtained for several members of the family which upon examination revealed highly heterogeneous phenotypes that prompted us to investigate the case further. Sequencing of the beta-globin gene and alpha cluster mapping in the propositus and his brother showed a previously undescribed beta-globin variant:Hb Iraq-Halabja, beta10(A7) Ala-->Val (GCC-->GTC), associated with beta0-thalassemia IVS-2 nt1 G-->A and either alpha-thal-2-3.7 kb deletion (brother), or alpha-globin gene triplication anti-3.7 kb type (propositus). Detailed functional studies of the variant gave a normal oxygenation curve, a normal heterotopic action of 2,3 DPG, and normal heat stability and isopropanol precipitation tests. The variant shows a clear difference in migration properties compared to normal beta-chain only when run on PAGE urea Triton. As expected, alpha/beta-globin mRNA ratios were influenced by the concomitant presence of an alpha-globin gene pathology and the beta0 thalassemia and not by the presence of the beta-globin variant which apparently is clinically silent.
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PMID:Hb Iraq-Halabja beta10 (A7) Ala-->Val (GCC-->GTC): a new beta-chain silent variant in a family with multiple Hb disorders. 1039 11

Hb Mont Saint-Aignan [beta128(H6)Ala-->Pro] is a mildly unstable variant, associated with hemolytic anemia, marked microcytosis and increased alpha/beta biosynthetic ratio (1.55 versus 1.1 +/- 0.1 in the control). The abnormal chain was isolated by selective precipitation with isopropanol and the structural modification determined by protein chemistry methods (reversed phase high performance liquid chromatography and mass spectrometry). Possible mechanisms underlying the beta(+)-thalassemia-like expression of this variant are discussed.
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PMID:Hb Mont Saint Aignan [beta128(H6)Ala-->Pro]: a new unstable variant leading to chronic microcytic anemia. 1130 Mar 50

We describe a hemoglobin beta-chain mutant detected incidentally in an unusual profile of glycated hemoglobin (HbA1c) measured by ion-exchange HPLC. Analysis of intact globin by electrospray ionization mass spectrometry (ESI-MS) and peptide analysis by on-line HPLC-ESI-MS-MS revealed the substitution, [beta111(G13)Val-->Ala], which was confirmed by DNA analysis. This was the second case of Hb Stanmore. As the first case combined beta(0)-thalassemia, and the family study in that case showed no case of Hb Stanmore without combined thalassemia, the case presented here is the first case of single heterozygote, and the first Japanese case. Hb Stanmore is isoelectrophoretically silent with only mild clinical symptoms, although stability by isopropanol test was positive.
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PMID:First case of a single heterozygote of an abnormal hemoglobin, Hb Stanmore, [beta111(G13)Val-->Ala]. 1282 94

We report a new unstable variant identified in three carriers of a family from East Sicily; it was named Hb Bronte after the place from which the family originated. DNA sequencing from nucleotides -181 to +894 (alpha1) and to +884 (alpha2) revealed a GTG-->GGG substitution at codon 93 of the alpha2-globin gene. The MCV and MCH values were at the lower end of the normal range in the carriers. On cation exchange high performance liquid chromatography (HPLC), the Hb A2 level was apparently increased to around 6%, and a small abnormal peak (0.3-0.4%) was detected after Hb A2. Two abnormal bands were detected by cellulose acetate electrophoresis: a major band (about 3-4%) migrated between Hb A and Hb F; a minor band (<1%) migrated between Hb A2 and carbonic anhydrase. Normal values of Hb A2 were detected by DEAE microchromatography. On reversed phase HPLC the variant chain was not detected, and most likely it was eluted with the alpha chain peak. The isopropanol stability test was very slightly positive in the carriers. Hemolytic symptoms were absent with the exception of indirect bilirubin, which was at high borderline in 2/3 carriers. In biosynthesis in vitro, the specific activity of the alpha chains was much higher than that of the beta-globin chains, and the alpha/beta biosynthetic ratio in the mother and proband was of the beta-thalassemia (thal) type (2.24 and 2.54, respectively). Time course experiments showed that the increase of the 3H-specific activity of the peak containing normal and variant alpha chains was not linear and was much higher than that of beta chains; moreover, the alpha/beta biosynthetic ratio varied during the 2 hours incubation.
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PMID:Hb Bronte or alpha93(FG5)Val-->Gly: a new unstable variant of the alpha2-globin gene, associated with a mild alpha(+)-thalassemia phenotype. 1290 99

We describe a 6-year-old girl and her mother with dominant beta-thalassemia due to hemoglobin Hradec Kralove (Hb HK). Both patients presented microcytic anemia, jaundice, splenomegaly, cholelithiasis, and recurrent hemolytic bouts. Osmotic resistance tests using saline and coiled planet centrifugation revealed the increased fragility of the red cell membrane. On the other hand, the glycerol lysing time was prolonged, and results of the isopropanol test were weakly positive. Despite mimicking the features of hereditary spherocytosis, the results of the genetic analyses verified the second reported family with Hb HK (codon 115, GCC [Ala] --> GAC [Asp]). Splenectomy was effective for the amelioration of hemolysis. Of 7 reported patients with Hb variants at beta-globin codon 115 (Hb Madrid and Hb HK), 5 underwent splenectomy. Because of the variable augmentation of extramedullary hemolysis in dominant beta-thalassemias, genotyping is necessary for determining the clinical indication of splenectomy.
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PMID:Dominant beta-thalassemia with hemoglobin Hradec Kralove: enhanced hemolysis in the spleen. 1468 90


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