Effect of Assorted Globin Haplotypes and α-Thalassemia on the Clinical Heterogeneity of Hb S-β-Thalassemia. (4th July 2018)

• Record Type: Journal Article
• Authors: Dash, Preetinanda M.; Sahu, Praveen K.; Patel, Siris; Mashon, Ranjeet S.; Kharat, Kiran R.; Mukherjee, Malay B.
• Is Part Of: Hemoglobin. Volume 42:Number 4(2018)
• Page Start: 236
• Page End: 242
• Publication Date: 2018-07-04
• Subjects: α-Thalassemia (α-thal) -- β-Thalassemia (β-thal) haplotype analysis -- Hb F -- IVS-I-5 (G>C) (HBB: c.95 + 5G>C) -- mutation -- Hb S (HBB: c.20A>T)- β-thal; Hemoglobinopathy -- Periodicals; Hemoglobin -- Periodicals; Hematology -- Periodicals; Thalassemia -- Periodicals; Blood -- Diseases -- Periodicals; 612.1111
• DOI: 10.1080/03630269.2018.1536666
• Languages: English
• ISSNs: 0363-0269

Abstract

Abstract: Hemoglobinopathies and thalassemias are the most commonly encountered monogenic disorders of blood in humans, posing a major genetic and public health problem round the globe. Hb S ( HBB : c.20A>T)-β-thalassemia (β-thal) is a compound aberrant heterozygosity with inconsistent phenotypic expression, which are poorly described and clinically mapped. Comprehensive genetic characterization of such a population is highly warranted for complete understanding of the clinical heterogeneity, disease prognosis and therapeutic management. In this study, Hb S-β-thal ( n = 60) patients, strictly defined by varying degrees of clinical presentations, were selected to evaluate their genotype-phenotype agreement. Furthermore, β-globin ( n = 120) and α-globin gene clusters ( n = 60) were genetically characterized and statistically correlated with clinical terminologies to explain the clinical heterogeneity. Our results revealed the association of the Arab-Indian haplotypes with nine different frameworks of β-thal together with the modulating role of α-thalassemia (α-thal). The study subjects, including carriers of β-thal haplotype III [– – – – – – –] (8.0%), presented with varying severe patterns of clinical symptoms such as painful crisis, multiple infections and splenomegaly, as an outcome of significantly less Hb F and higher Hb S levels ( p < 0.5). The study findings indicated that together with α-thal, β-thal haplotypes and Hb F levels, may possibly provide a close justification to support the clinical heterogeneity in the study population.