Genetic modifiers of beta-thalassemia.
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TLDR
The clinical and hematologic diversity encountered in beta thalassemia is reviewed with an overview of the modifier genes that moderate their disease expression.Abstract:
As the defective genes for more and more genetic disorders become unravelled, it is clear that patients with apparently identical genotypes can have many different clinical conditions even in simple monogenic disorders. Beta thalassemia occurs when there is a deficiency in the synthesis of beta globin chains. The clinical manifestations of beta thalassemia are extremely diverse, spanning a broad spectrum from severe anemia and transfusion-dependency to the asymptomatic state of thalassemia trait. The remarkable phenotypic diversity of the beta thalassemias is prototypical of how a wide spectrum of disease severity can be generated in single gene disorders. The most reliable and predictive factor of disease phenotype is the nature of the mutation at the beta globin locus itself. However, relating phenotype to genotype is complicated by the complex interaction of the environment and other genetic factors at the secondary and tertiary levels, some implicated from family studies, and others, as yet unidentified. This article reviews the clinical and hematologic diversity encountered in beta thalassemia with an overview of the modifier genes that moderate their disease expression.read more
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Journal ArticleDOI
Molecular therapies in beta-thalassaemia
TL;DR: Improved understanding of the pathophysiology and molecular basis of the disease has provided clues for more effective strategies that aim to correct the defect in β‐ globin chain synthesis at the primary level or redress the α/β‐globin chain imbalance at the secondary level.
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Beta-thalassemia: from genotype to phenotype
TL;DR: Beta-thalassemias are heterogeneous autosomal recessive hereditary anemias characterized by reduced or absent β globin chain synthesis, and the resulting relative excess of unbound α globin chains precipitate in erythroid precursors in the bone marrow, leading to their premature death and, hence, to premature death.
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FOXO3-mTOR metabolic cooperation in the regulation of erythroid cell maturation and homeostasis
Xin Zhang,Genis Camprecios,Pauline Rimmele,Raymond Liang,Safak Yalcin,Sathish Kumar Mungamuri,Jeffrey Barminko,Valentina d'Escamard,Margaret H. Baron,Carlo Brugnara,Dmitri Papatsenko,Stefano Rivella,Saghi Ghaffari +12 more
TL;DR: The combined findings indicate that a metabolism‐mediated regulatory network centered by FOXO3 and mTOR control the balanced production and maturation of erythroid cells and indicates that alteration in the function of this network might be implicated in the pathogenesis of ineffective erythropoiesis.
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Genotype and phenotype characterizations in a large cohort of β-thalassemia heterozygote with different forms of α-thalassemia in northeast Thailand.
TL;DR: The findings underline the heterogeneity of β-thalassemia and the importance of hematological and molecular analyses of both α-and β -thalassemias in the diagnosis and genetic counseling of the couples at-risk of having babies with severe thalassemia diseases in the region.
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The molecular basis of beta-thalassemia intermedia in southern China: genotypic heterogeneity and phenotypic diversity
Wanqun Chen,Wanqun Chen,Xinhua Zhang,Xuan Shang,Ren Cai,Liyan Li,Tianhong Zhou,Man-na Sun,Fu Xiong,Xiangmin Xu +9 more
TL;DR: The clinical outcomes of Chinese TI patients were mostly explained by the genotypes linked to the β- and α-globin gene cluster, and the existence of other causative genetic determinants is remaining to be molecularly defined.
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