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Martin H Steinberg - One of the best experts on this subject based on the ideXlab platform.

  • the genetics of Hemoglobin A2 regulation in sickle cell anemia
    American Journal of Hematology, 2014
    Co-Authors: Paula J Griffin, Paola Sebastiani, Heather L Edward, Clinton T Baldwin, Mark T Gladwin, Victor R Gordeuk, David H K Chui, Martin H Steinberg
    Abstract:

    Hemoglobin A2, a tetramer of α- and δ-globin chains, comprises less than 3% of total Hemoglobin in normal adults. In northern Europeans, single nucleotide polymorphisms (SNPs) in the HBS1L-MYB locus on chromosome 6q and the HBB cluster on chromosome 11p were associated with HbA2 levels. We examined the genetic basis of HbA2 variability in sickle cell anemia using genome-wide association studies. HbA2 levels were associated with SNPs in the HBS1L-MYB interval and SNPs in BCL11A. These effects are mediated by the association of these loci with γ-globin gene expression and fetal Hemoglobin (HbF) levels. The association of polymorphisms downstream of the β-globin gene (HBB) cluster on chromosome 11 with HbA2 was not mediated by HbF. In sickle cell anemia, levels of HbA2 appear to be modulated by trans-acting genes that affect HBG expression and perhaps also elements within the β-globin gene cluster. HbA2 is expressed pancellularly and can inhibit HbS polymerization. It remains to be seen if genetic regulators of HbA2 can be exploited for therapeutic purposes. Am. J. Hematol. 89:1019–1023, 2014. © 2014 Wiley Periodicals, Inc.

  • β thalassemia intermedia with exceptionally high Hemoglobin A2 relationship to mutations in the β gene promoter
    The American Journal of the Medical Sciences, 1992
    Co-Authors: M B Coleman, Junius G Adams, M W Plonczynski, A H Harrell, Alice M Walker, Virgil Fairbanks, Martin H Steinberg
    Abstract:

    Small deletions of the 5' portion of the beta-globin gene that remove the promoters but stop 3' to the delta-globin gene are recognized as the sole cause of beta-thalassemia with exceptionally high Hemoglobin A2 (HbA2) levels. Two patients with beta-thalassemia intermedia and exceptionally high levels of HbA2 (10.4 and 12.0%) were examined. One patient was a combined heterozygote for the -88 C----T and a novel -87 C----A mutation, while the other was homozygous for the -29 A----G beta(+)-thalassemia mutation. The remainder of the beta genes were normal. There was no evidence for deletions involving the 5' portion of the beta gene or the region between the beta and delta genes. Gene mapping studies excluded the possibility of a beta delta-anti-Lepore Hemoglobin gene with beta promoters and delta coding sequences. There were no mutations in the promoters of the G gamma or A gamma-globin genes that have been associated with the hereditary persistence of HbF phenotype. The delta-globin gene promoters were normal from codon 17 to position -145 relative to the mRNA capping site. There appears to be considerable heterogeneity of HbA2 and HbF levels in patients who are homozygous or mixed heterozygotes for mutations in the TATA box and other promoter elements of the beta-globin gene. The capacity for proteolysis within the erythrocyte may vary among individuals. The authors hypothesize that in the exceptionally high HbA2 beta-thalassemia intermedia phenotype, proteolysis of superfluous alpha-globin chains is less efficient than in patients with customary levels of HbA2.(ABSTRACT TRUNCATED AT 250 WORDS)

  • high Hemoglobin A2 beta 0 thalassemia due to a 532 basepair deletion of the 5 beta globin gene region
    Blood, 1991
    Co-Authors: John S Waye, David H K Chui, Junius G Adams, Shiping Cai, Barry Eng, Cathy Clark, Martin H Steinberg
    Abstract:

    ETA-THALASSEMIA is an autosomal recessive disB ease characterized by a deficiency (P’-thalassemia) or absence ( Po-thalassemia) of p-globin chain synthesis. In general, the Po- and P’-thalassemia mutations are caused by base substitutions and small insertions or deletions in the P-globin gene. Almost 100 such mutations have now been reported.’.’ In addition, there are larger deletions that result in P”-thalassemia. In this report, we identify and characterize a Pothalassemia mutation caused by a deletion of the 5’ coding region of the P-globin gene and several hundred basepairs (bp) of upstream sequences. In the heterozygote, this deletion is associated with an unusually high level of Hemoglobin (Hb) A, and typical P-thalassemia trait. The endpoints of this new P-globin gene deletion reaffirm the notion that removal of the 5’ region of the P-globin gene and adjacent upstream sequences is associated with elevated Hb A, levels, and further localize the essential sequences that, when deleted, can lead to this phenotypic anomaly.

Mario Pirastu - One of the best experts on this subject based on the ideXlab platform.

Usha Rusia - One of the best experts on this subject based on the ideXlab platform.

  • phenotypic expression of Hemoglobin A2 in beta thalassemia trait with iron deficiency
    Annals of Hematology, 1998
    Co-Authors: N Madan, Meera Sikka, S Sharma, Usha Rusia
    Abstract:

    Iron status was estimated in 463 heterozygous beta-thalassemics to delineate the effect of iron deficiency on the expression of Hemoglobin A2 (HbA2) in these patients. One hundred and twenty-six (27.2%) patients with the trait were iron deficient. These iron-deficient patients had a significantly (p 3.5%) in all but one heterozygote investigated. Mean HbA2/cell was significantly (p < 0.05) lower in BTT patients with iron deficiency than in patients without iron deficiency. The presence of iron deficiency did not preclude the detection of BTT in this population. The effect of iron deficiency in BTT was apparent as a significant lowering of the Hb concentration and an increased prevalence of anemia. Iron therapy is warranted for BTT patients with iron-deficiency traits and would help to significantly raise their Hb concentration. The elevation of HbA2 was striking and could be used with reliability in making the diagnosis of BTT even in the presence of iron deficiency.

Fevziye Gülçin Turhan - One of the best experts on this subject based on the ideXlab platform.

  • depression in subjects with beta thalassemia minor
    Annals of Hematology, 2013
    Co-Authors: Şakir Özgür Keşkek, Sinan Kırım, Ali Turhan, Fevziye Gülçin Turhan
    Abstract:

    Beta-thalassemia minor is a common genetic blood disorder in Mediterranean countries such as Turkey. Additionally, depression is one of the most widespread mental disorders that affect people worldwide, and its prevalence is increasing with co-occurring medical conditions. The aim of this study was to determine whether the frequency of depression is elevated in subjects with beta-thalassemia minor. A total of 106 subjects were included in this study, of which 53 participants were diagnosed with beta-thalassemia minor. The other 53 participants were otherwise healthy. Hemoglobin electrophoresis and a complete blood count were performed in all subjects, and all participants were evaluated using the Hamilton Depression Rating Scale (HDRS). The HDRS scores of the subjects with beta-thalassemia minor were higher than those in the healthy subjects (p < 0.001). Additionally, the Hemoglobin A2 levels were positively associated with the HDRS scores (p < 0.0001, r = 0.482). This study suggests a possible association between depression and beta-thalassemia minor, in which the risk of depression may be increased in subjects with this condition.

Supan Fucharoen - One of the best experts on this subject based on the ideXlab platform.

  • icsh recommendations for assessing automated high performance liquid chromatography and capillary electrophoresis equipment for the quantitation of hbA2
    International Journal of Laboratory Hematology, 2015
    Co-Authors: A D Stephens, Roshan B Colah, Supan Fucharoen, James D Hoyer, D Keren, A Mcfarlane, D Perrett, B Wild
    Abstract:

    Summary Automated high performance liquid chromatography and Capillary electrophoresis are used to quantitate the proportion of Hemoglobin A2 (HbA2) in blood samples order to enable screening and diagnosis of carriers of β-thalassemia. Since there is only a very small difference in HbA2 levels between people who are carriers and people who are not carriers such analyses need to be both precise and accurate. This paper examines the different parameters of such equipment and discusses how they should be assessed.

  • known and new Hemoglobin A2 variants in thailand and implication for β thalassemia screening
    Clinica Chimica Acta, 2015
    Co-Authors: Sitthichai Panyasai, Goonnapa Fucharoen, Supan Fucharoen
    Abstract:

    Abstract Background We reported molecular and hematological characteristics of δ-globin chain variants and addressed diagnostic consideration of complex Hemoglobinopathies caused by their interactions with α- and β-thalassemias. Methods Study was done on four unrelated Thai subjects with second Hb A 2 fractions. Hb analysis was carried out using automated HPLC and capillary electrophoresis. Mutations were identified by DNA analysis. Novel diagnostic methods based on PCR-RFLP and allele specific PCR were developed. Results Hb analysis revealed Hb A 2 variant in all cases. DNA analysis of δ-globin gene identified the Hb A 2 -Melbourne [δ43(CD2)Glu→ Lys] in combination with α + -thalassemia, α 0 -thalassemia and β 0 -thalassemia in the first three cases, respectively. Analysis of the remaining case identified a novel δ-Hb variant namely the Hb A 2 -Lampang [δ47(CD6) G AT→ A AT; Asp → Asn] found in association with Hb E and α + -thalassemia. These mutations could be identified using PCR-RFLP and allele specific PCR assays developed. Conclusions It is necessary to recognize the Hb A 2 variant and to combine the amounts of Hb A 2 and Hb A 2 -variant for a total Hb A 2 value to make better diagnostic of these complex syndromes. Co-inheritance of these multiple globin gene defects could lead to complex Hemoglobinopathies requiring comprehensive Hb and molecular assessments.