Molecular Basis of Thalassemia

Grosso, Michela; Sessa, Raffaele; Puzone, Stella; Storino, Maria Rosaria; Izzo, Paola

doi:10.5772/31362

Cited by 8 publications

(9 citation statements)

References 35 publications

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“…It might also impact on patients with hemoglobin disorders, such as thalassemia [1]. Indonesia has one of the highest prevalence of thalassemia globally [2].…”

mentioning

confidence: 99%

Thalassemic Child Presenting with Anosmia due to COVID-19

et al. 2020

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“…It might also impact on patients with hemoglobin disorders, such as thalassemia [1]. Indonesia has one of the highest prevalence of thalassemia globally [2].…”

mentioning

confidence: 99%

Thalassemic Child Presenting with Anosmia due to COVID-19

et al. 2020

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“…Most of the severity and haematological pictures observed in α-thalassaemia are associated with the extended range of cellular defects, described by partial or complete absence of the α-globin genes [14]. Deletion of one (−α/αα) or two αglobin (−−/αα, −α/−α) genes leads to asymptomatic forms of alpha thalassaemia known as silent carrier and thalassaemia trait, respectively.…”

Section: Genotypic and Phenotypic Correlation Of α-Thalassaemiamentioning

confidence: 99%

“…An imbalance in the expression of globin genes from either side results in thalassaemia the deletional types. This could be attributed to the fact that non-deletional mutations are mostly associated with genomic regions that are critical for normal expression of αglobin genes; oligonucleotide insertions and deletion [14]. The clinical manifestations of Hb H disease look like those of α-thalassaemia intermedia, which is described by a considerable variable extent of anaemia.…”

Section: Genotypic and Phenotypic Correlation Of α-Thalassaemiamentioning

confidence: 99%

“…Hb H individuals may typically have hepatosplenomegaly, variable forms of jaundice, gallstones, and haemolytic crisis that may be fuelled by infections or drug therapy. While β-thalassaemia conditions are associated with ineffective erythropoiesis, in αthalassaemia, the major cause of anaemia is due to haemolysis [14]. A complete absence of α-globin chain synthesis leads to Hb Bart's hydrops foetalis, which is attributed to the inheritance of two α 0 -thalassaemia phenotypes.…”

Section: Genotypic and Phenotypic Correlation Of α-Thalassaemiamentioning

confidence: 99%

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Non-deletional alpha thalassaemia: a review

Kwaifa

Lai

Noor

2020

Orphanet J Rare Dis

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Background: Defective synthesis of the α-globin chain due to mutations in the alpha-globin genes and/or its regulatory elements leads to alpha thalassaemia syndrome. Complete deletion of the 4 alpha-globin genes results in the most severe phenotype known as haemoglobin Bart's, which leads to intrauterine death. The presence of one functional alpha gene is associated with haemoglobin H disease, characterised by non-transfusion-dependent thalassaemia phenotype, while silent and carrier traits are mostly asymptomatic.Main body: Clinical manifestations of non-deletional in alpha thalassaemia are varied and have more severe phenotype compared to deletional forms of alpha thalassaemia. Literature for the molecular mechanisms of common non-deletional alpha thalassaemia including therapeutic measures that are necessarily needed for the understanding of these disorders is still in demand. This manuscript would contribute to the better knowledge of how defective production of the α-globin chains due to mutations on the alpha-globin genes and/or the regulatory elements leads to alpha thalassaemia syndrome. Conclusion:Since many molecular markers are associated with the globin gene expression and switching over during the developmental stages, there is a need for increased awareness, new-born and prenatal screening program, especially for countries with high migration impact, and for improving the monitoring of patients with αthalassaemia.

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“…As with βthalassemia, α-thalassemias are characterized by absent (α 0 -thalassemia) or reduced (α +thalassemia) production of α-globin chains, thus resulting in globin chain imbalance. The majority of the α-thalassemia defects result from deletions involving one or both α-globin genes on the same chromosome whereas point mutations affecting the functional expression of one of the two α-globin genes are not as common [24].…”

Section: α-Globin Genesmentioning

confidence: 99%

Novel Therapy Approaches in β-Thalassemia Syndromes — A Role of Genetic Modifiers

Pavlović¹,

Ugrin²,

Stojiljković³

2015

Inherited Hemoglobin Disorders

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The β-thalassemia syndromes are heterogeneous autosomal recessive hereditary disorders, caused by alterations in the HBB gene and characterized by absent or reduced β-globin chain synthesis. The β-thalassemia phenotypes are variable, ranging from severe, transfusion-dependent thalassemia major to mild, asymptomatic thalassemia trait. This interpatient clinical variability has swayed researchers toward identifying genetic modifiers for these disorders. Primary modifiers refer to type of alterations affecting β-globin gene. Secondary modifiers include variations in genes affecting α/β-globin chain equilibrium, such as genes involved in the γ-globin gene expression and genes affecting the amount and stability of α-globin chains. Tertiary modifiers are gene variations affecting the phenotype with regard to the complications caused by β-thalassemia syndromes. A role of secondary genetic modifiers in ameliorating the clinical phenotype has been observed. Secondary genetic modifiers are the most common targets for modern therapy and could be located within α-and γ-globin genes or outside globin gene cluster. The most potent secondary modifier genes are γ-globin genes. Production of fetal hemoglobin (HbF) trough adulthood ameliorates the severity of β-thalassemia phenotype. Large family and genome-wide association studies have shown that regions outside of the β-globin gene cluster are also implicated in γ-globin gene expression regulation. HBS1-MYB intragenic region and BCL11A gene have been particularly studied. Variants within these loci, along with γ-globin gene variants, account for approximately 50% of the HbF level variation, suggesting that additional factors are involved (transcription regulators (KLF1), regulators of α-globin chain stability (AHSP), epigenetic regulators (FoP)). Until recently a definitive cure for β-thalassemia could be achieved with bone marrow transplantation. However, it is available for less than 30% of the patients and bears a significant risk of morbidity and mortality. Alternative strategies, such as gene

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Molecular Basis of Thalassemia

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Cited by 8 publications

References 35 publications

Thalassemic Child Presenting with Anosmia due to COVID-19

Thalassemic Child Presenting with Anosmia due to COVID-19

Non-deletional alpha thalassaemia: a review

Novel Therapy Approaches in β-Thalassemia Syndromes — A Role of Genetic Modifiers

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