Global distribution of β-thalassemia mutations: An update

Rao, Ekta; Kumar Chandraker, Sandip; Misha Singh, Mable; Kumar, Ravindra

doi:10.1016/j.gene.2023.148022

Cited by 22 publications

(11 citation statements)

References 112 publications

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“…Five HBB gene variants account for approximately 85% of all β-thalassemia variants in Croatian population. These findings are in accordance with the observation that each population has a few common variants [13], that enables the choice for the population-specific targeted carrier screening methods. Although thalassemia is sporadic in Croatia, the results might provide information on the history and origin of the different β-thalassemia variants.…”

Section: Discussionsupporting

confidence: 89%

“…The molecular basis of β-thalassemias has been studied in many countries. Only 20 variants account for more than 80% of the β-thalassemia variants worldwide due to geographical clustering, where each population has a few common variants and a varying number of rare ones [13]. Hb Lepore-BW is the predominant cause of  -thalassemia in Croatia with the frequency of 32,6%.…”

Section: Discussionmentioning

confidence: 99%

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The Relevance of β-Thalassemia Heterozygosity in Pediatric Clinical Practice: Croatian Experience

Dordevic,

Ugrin,

Mrakovcic Sutic

et al. 2024

Preprint

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Thalassemia syndromes are common monogenic disorders that represent a significant global health issue. No systematic epidemiological and molecular investigations on thalassemias in Croatian population have been reported to date. This prospective study included 70 children with a presumptive diagnosis of thalassemia, and their 42 first-degree relatives. Molecular characterization was performed using direct sequencing and gap-PCR methods. We identified 46 (30 children and 16 first-degree relatives) β-thalassemia heterozygous carriers from 24 unrelated families, carrying eight different mutations and one hemoglobin variant. Five variants account for approximately 85% of all affected β-globin alleles: Hb Lepore-Boston-Washington (32,6%), HBB: c.93-21G&gt;A (19,6%), HBB:c.315+1G&gt;A (13,1%), HBB:c.92+1G&gt;A (10,9%), and HBB:c.92+6T&gt;C variant (8,7%). A need for more detailed genetic profiling of β-thalassemia carriers is emphasized since genetic modifiers can significantly impact their phenotype. Our study provides important new insights into the relevance of β-thalassemia heterozygosity in the pediatric clinical practice.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

The Relevance of β-Thalassemia Heterozygosity in Pediatric Clinical Practice: Croatian Experience

Dordevic,

Ugrin,

Mrakovcic Sutic

et al. 2024

Preprint

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“…The hereditary β-thalassemia syndromes are primarily caused by mutations of the b-globin gene (HBB) [ 1 , 2 , 3 ]. Interestingly, about 20 HBB gene variants (of the more than 350 variants reported so far) account for more than 80% of the β-thalassemia variants worldwide [ 4 , 5 ]. These variants cause a large variety of phenotype alterations, leading to low or absent production of the β-globin polypeptide chain and, hence adult hemoglobin (HbA, α 2 β 2 ) [ 1 , 2 ].…”

Section: Genetics Pathophysiology and Clinical Picture Of Beta-thalas...mentioning

confidence: 99%

Impact of α-Globin Gene Expression and α-Globin Modifiers on the Phenotype of β-Thalassemia and Other Hemoglobinopathies: Implications for Patient Management

Traeger-Synodinos,

Vrettou,

Sofocleous

et al. 2024

IJMS

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In this short review, we presented and discussed studies on the expression of globin genes in β-thalassemia, focusing on the impact of α-globin gene expression and α-globin modifiers on the phenotype and clinical severity of β-thalassemia. We first discussed the impact of the excess of free α-globin on the phenotype of β-thalassemia. We then reviewed studies focusing on the expression of α-globin-stabilizing protein (AHSP), as a potential strategy of counteracting the effects of the excess of free α-globin on erythroid cells. Alternative processes controlling α-globin excess were also considered, including the activation of autophagy by β-thalassemia erythroid cells. Altogether, the studies reviewed herein are expected to have a potential impact on the management of patients with β-thalassemia and other hemoglobinopathies for which reduction in α-globin excess is clinically beneficial.

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“…The variability of biomarkers among patients is a factor to be considered to obtain, for single protocols, the highest probability to reach positive effects on the highest number of treated patients [22]. This research activity involves interdisciplinary collaborations between researchers working in genetics, molecular biology, pharmacology, pharmaceutics, and organic chemistry and it is expected to discover useful information on the mechanisms of drug action (e.g., pharmacodynamics and pharmacokinetics), the identification of novel molecular targets, and the design of novel biomedicines [3][4][5]. Furthermore, the clinical application for the prediction of toxicity risk or beneficial effects could be helpful in numerous ways for several pathologies, including hemoglobinopathies [13,20,[23][24][25][26][27].…”

Section: Pharmacogenomicsmentioning

confidence: 99%

“…The phenotype of β-thalassemia is primarily characterized by a low or absent production of adult hemoglobin (HbA) due to low or absent production of β-globin, leading to an excess of free α-globin chains with associated ineffective erythropoiesis [1]. This β-thalassemia phenotype is caused by more than 350 mutations of the adult β-globin gene [1,[3][4][5]. The phenotype of SCD is characterized by the presence of a mutated β-globin chain with the replacement (due to a mis-sense point mutation of the β-globin gene) of glutamic acid with valine in the sixth position of the protein, originating the so-called Sickle hemoglobin (HbS) [6].…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenomics of Drugs Used in β-Thalassemia and Sickle-Cell Disease: From Basic Research to Clinical Applications

Gambari,

Waziri,

Goonasekera

et al. 2024

IJMS

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In this short review we have presented and discussed studies on pharmacogenomics (also termed pharmacogenetics) of the drugs employed in the treatment of β-thalassemia or Sickle-cell disease (SCD). This field of investigation is relevant, since it is expected to help clinicians select the appropriate drug and the correct dosage for each patient. We first discussed the search for DNA polymorphisms associated with a high expression of γ-globin genes and identified this using GWAS studies and CRISPR-based gene editing approaches. We then presented validated DNA polymorphisms associated with a high HbF production (including, but not limited to the HBG2 XmnI polymorphism and those related to the BCL11A, MYB, KLF-1, and LYAR genes). The expression of microRNAs involved in the regulation of γ-globin genes was also presented in the context of pharmacomiRNomics. Then, the pharmacogenomics of validated fetal hemoglobin inducers (hydroxyurea, butyrate and butyrate analogues, thalidomide, and sirolimus), of iron chelators, and of analgesics in the pain management of SCD patients were considered. Finally, we discuss current clinical trials, as well as international research networks focusing on clinical issues related to pharmacogenomics in hematological diseases.

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Global distribution of β-thalassemia mutations: An update

Cited by 22 publications

References 112 publications

The Relevance of β-Thalassemia Heterozygosity in Pediatric Clinical Practice: Croatian Experience

The Relevance of β-Thalassemia Heterozygosity in Pediatric Clinical Practice: Croatian Experience

Impact of α-Globin Gene Expression and α-Globin Modifiers on the Phenotype of β-Thalassemia and Other Hemoglobinopathies: Implications for Patient Management

Pharmacogenomics of Drugs Used in β-Thalassemia and Sickle-Cell Disease: From Basic Research to Clinical Applications

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