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
Citations
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Journal ArticleDOI
The α-Thalassemias
TL;DR: More than 100 varieties of α-thalassemia have been identified and their geographic distribution and the challenges associated with screening, diagnosis, and management suggest they should have a higher priority on global public health agendas.
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A genome-wide association identified the common genetic variants influence disease severity in β0-thalassemia/hemoglobin E
Manit Nuinoon,Wattanan Makarasara,Taisei Mushiroda,Iswari Setianingsih,Pustika Amalia Wahidiyat,Orapan Sripichai,Natsuhiko Kumasaka,Atsushi Takahashi,Saovaros Svasti,Thongperm Munkongdee,Surakameth Mahasirimongkol,Chayanon Peerapittayamongkol,Vip Viprakasit,Naoyuki Kamatani,Pranee Winichagoon,Michiaki Kubo,Yusuke Nakamura,Suthat Fucharoen +17 more
TL;DR: It is revealed that all the three reported loci and the α-globin gene locus are the best and common predictors of the disease severity in β-thalassemia.
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Molecular Basis of Thalassemia
TL;DR: The complex and heterogeneous spectrum of molecular defects underlying these inherited conditions is regionally specific and in most cases the geographic and ethnic distributions have been determined, providing support for prevention programs based on screening, genetic counselling and prenatal diagnosis in couples at risk.
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The role of haemoglobin A(2) testing in the diagnosis of thalassaemias and related haemoglobinopathies.
TL;DR: Comments on the need for accuracy and standardisation are included and a practical flow-chart is presented to summarise the significance of HbA2 estimation in different thalassaemia syndromes and related haemoglobinopathies.
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Petros Kountouris,Carsten W. Lederer,Pavlos Fanis,Xenia Feleki,John M. Old,Marina Kleanthous +5 more
TL;DR: IthaGenes is a new interactive database of haemoglobin variations, which stores information about genes and variations affecting ha Hemoglobin disorders, while embedding the NCBI Sequence Viewer for graphical representation of each variation.
References
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TL;DR: DNA–protein interaction and transactivation analysis correlated the decrease in the β‐globin synthesis with the reduced binding and trans activation of EKLF to the mutant promoter, predicting that the β•101C→G mutation will display a silent thalassemia phenotype similar to that of the β-101C–T mutation.
Journal ArticleDOI
A novel mechanism for thalassaemia intermedia.
Catherine Badens,Marie-Geneviève Mattei,AM Imbert,Claudine Lapoumeroulie,N. Martini,Gérard Michel,D Lena-Russo +6 more
TL;DR: It is found that a somatic deletion of the beta-globin gene in the haemopoietic lineage of a heterozygous beta-thalassaemic patient gives rise to a mosaic of cells with either one or no functional beta- globin gene and it extends to a region of frequent loss of heterozygosity called LOH11A, which is located close to the Beta-Globin locus.
Journal ArticleDOI
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