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Human Genomics Jun 2021For decades, various strategies have been proposed to solve the enigma of hemoglobinopathies, especially severe cases. However, most of them seem to be lagging in terms... (Review)
Review
For decades, various strategies have been proposed to solve the enigma of hemoglobinopathies, especially severe cases. However, most of them seem to be lagging in terms of effectiveness and safety. So far, the most prevalent and promising treatment options for patients with β-types hemoglobinopathies, among others, predominantly include drug treatment and gene therapy. Despite the significant improvements of such interventions to the patient's quality of life, a variable response has been demonstrated among different groups of patients and populations. This is essentially due to the complexity of the disease and other genetic factors. In recent years, a more in-depth understanding of the molecular basis of the β-type hemoglobinopathies has led to significant upgrades to the current technologies, as well as the addition of new ones attempting to elucidate these barriers. Therefore, the purpose of this article is to shed light on pharmacogenomics, gene addition, and genome editing technologies, and consequently, their potential use as direct and indirect genome-based interventions, in different strategies, referring to drug and gene therapy. Furthermore, all the latest progress, updates, and scientific achievements for patients with β-type hemoglobinopathies will be described in detail.
Topics: Anemia, Sickle Cell; Gene Editing; Genetic Therapy; Hemoglobinopathies; Humans; beta-Globins; beta-Thalassemia
PubMed: 34090531
DOI: 10.1186/s40246-021-00329-0 -
The Lancet. Global Health Jan 2022
Topics: Developing Countries; Hemoglobin, Sickle; Hemoglobinopathies; Humans; Infant, Newborn; Neonatal Screening
PubMed: 34919844
DOI: 10.1016/S2214-109X(21)00559-3 -
Blood Cells, Molecules & Diseases May 2018
Topics: Animals; Genetic Association Studies; Genetic Predisposition to Disease; Globins; Hemoglobinopathies; Humans
PubMed: 28214138
DOI: 10.1016/j.bcmd.2017.02.002 -
Scientific Reports Mar 2019Thalassemia and hemoglobinopathy are two common inherited disorders, which are highly prevalent in southern China. However, there is little knowledge on the genotypes of...
Thalassemia and hemoglobinopathy are two common inherited disorders, which are highly prevalent in southern China. However, there is little knowledge on the genotypes of thalassemia and hemoglobinopathy in Southeastern China. In this study, we present a large-scale genetic detection and molecular characterization of thalassemia and hemoglobinopathy in Fujian province, Southeastern China. A total of 189414 subjects screened for thalassemia were recruited, and the hemoglobin components and levels were investigated. Furthermore, suspected common thalassemia was identified, and the suspected rare forms of common thalassemias and hemoglobinopathy were detected. Among the total subjects screened, the overall prevalence of thalassemia and hemoglobinopathy was 6.8% and 0.26%, and rare α-thalassemia genotypes HKαα, -/αα and -α/αα, and novel β-thalassemia gene mutations CD90(G → T) and IVS-I-110(G > A) were identified. Additionally, Hb Q-Thailand hemoglobinopathy and five other types of hemoglobinopathies (Hb New York, Hb J-Bangkok, Hb G-Taipei, Hb G-Coushatta and Hb Maputo) were found. The results of this 10-year large-scale study demonstrate high prevalence of thalassemia with complicated gene mutations in Southeastern China, which provides valuable baseline data for genetic counseling and prenatal diagnosis. In addition to detection of common thalassemia genes, detection of rare thalassemia genotypes and hemoglobinopathies is recommended.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; China; Female; Genotype; Hemoglobinopathies; Hemoglobins, Abnormal; Humans; Infant; Male; Middle Aged; Polymorphism, Single Nucleotide; Prevalence; Thy-1 Antigens; Young Adult; alpha-Thalassemia; beta-Thalassemia
PubMed: 30837609
DOI: 10.1038/s41598-019-40089-5 -
Journal of Diabetes Science and... Jan 2020
Topics: Diabetes Mellitus; Glycated Hemoglobin; Hemoglobinopathies; Humans
PubMed: 30897962
DOI: 10.1177/1932296819841698 -
Orphanet Journal of Rare Diseases Jul 2023Inherited blood disorders affect 7% of the population worldwide, with higher prevalences in countries in the "thalassemia belt," which includes Bangladesh. Clinical... (Clinical Trial)
Clinical Trial
BACKGROUND
Inherited blood disorders affect 7% of the population worldwide, with higher prevalences in countries in the "thalassemia belt," which includes Bangladesh. Clinical management options for severely affected individuals are expensive; thus, targeted government policies are needed to support prevention and treatment programs. In Bangladesh, there is a lack of data, in particular community-based estimates, to determine population prevalence. This study aims to estimate the prevalence of a wide range of hemoglobinopathies and their associations with anemia in a community-based sample of women and young children in rural Sylhet, Bangladesh.
METHODS
Capillary blood samples from 900 reproductive-aged women and 395 children (aged 6-37 months) participating in the Food and Agricultural Approaches to Reducing Malnutrition (FAARM) trial in two sub-districts of Habiganj, Sylhet Division, Bangladesh were analyzed for alpha thalassemia, beta thalassemia, and other hemoglobinopathies. We examined the association of each inherited blood disorder with hemoglobin concentration and anemia using linear and logistic regression.
RESULTS
We identified at least one inherited blood disorder in 11% of women and 10% of children. Alpha thalassemia was most prevalent, identified in 7% of women and 5% of children, followed by beta thalassemia and hemoglobin E in 2-3%. We also identified cases of hemoglobin S and hemoglobin D in this population. Having any of the identified inherited blood disorders was associated with lower hemoglobin values among non-pregnant women, largely driven by alpha and beta thalassemia. Pregnant women with beta thalassemia were also more likely to have lower hemoglobin concentrations. Among children, we found weak evidence for a relationship between hemoglobinopathy and lower hemoglobin concentrations.
CONCLUSIONS
We found a high prevalence of alpha thalassemia among both women and children in rural Sylhet, Bangladesh-higher than all other identified hemoglobinopathies combined. Community-based estimates of alpha thalassemia prevalence in Bangladesh are scarce, yet our findings suggest that alpha thalassemia may comprise the majority of inherited blood disorders in some regions of the country. We recommend that future research on inherited blood disorders in Bangladesh include estimates of alpha thalassemia in their reporting for public health awareness and to facilitate couples counseling.
Topics: Adult; Child, Preschool; Female; Humans; Infant; alpha-Thalassemia; Bangladesh; beta-Thalassemia; Hemoglobinopathies; Prevalence
PubMed: 37468973
DOI: 10.1186/s13023-023-02821-3 -
Genes Feb 2023Beta-like globin gene expression is developmentally regulated during life by transcription factors, chromatin looping and epigenome modifications of the β-globin locus.... (Review)
Review
Beta-like globin gene expression is developmentally regulated during life by transcription factors, chromatin looping and epigenome modifications of the β-globin locus. Epigenome modifications, such as histone methylation/demethylation and acetylation/deacetylation and DNA methylation, are associated with up- or down-regulation of gene expression. The understanding of these mechanisms and their outcome in gene expression has paved the way to the development of new therapeutic strategies for treating various diseases, such as β-hemoglobinopathies. Histone deacetylase and DNA methyl-transferase inhibitors are currently being tested in clinical trials for hemoglobinopathies patients. However, these approaches are often uncertain, non-specific and their global effect poses serious safety concerns. Epigenome editing is a recently developed and promising tool that consists of a DNA recognition domain (zinc finger, transcription activator-like effector or dead clustered regularly interspaced short palindromic repeats Cas9) fused to the catalytic domain of a chromatin-modifying enzyme. It offers a more specific targeting of disease-related genes (e.g., the ability to reactivate the fetal γ-globin genes and improve the hemoglobinopathy phenotype) and it facilitates the development of scarless gene therapy approaches. Here, we summarize the mechanisms of epigenome regulation of the β-globin locus, and we discuss the application of epigenome editing for the treatment of hemoglobinopathies.
Topics: Humans; Epigenesis, Genetic; Epigenome; Hemoglobinopathies; beta-Globins; Chromatin; DNA
PubMed: 36980849
DOI: 10.3390/genes14030577 -
The Israel Medical Association Journal... Dec 2014
Topics: Cyanosis; Diagnosis, Differential; Dyspnea; Hemoglobinopathies; Hemoglobins, Abnormal; Humans; Mutation; Oximetry; Oxygen
PubMed: 25630210
DOI: No ID Found -
Hematology/oncology and Stem Cell... Dec 2017Kuwait is located in the Arabian Gulf and has a population of 3.5million. The stem cell transplantation program started in 2000. Autologous peripheral blood stem cell... (Review)
Review
Kuwait is located in the Arabian Gulf and has a population of 3.5million. The stem cell transplantation program started in 2000. Autologous peripheral blood stem cell transplantation started first, as it was easier technically to establish. In 2011, the allogeneic program started with focus on acute leukemia and hemoglobinopathies. The success of both programs required teamwork and support of health planners. The Kuwait National Bone Marrow Registry was established in 2012. The issue of donor availability and drug shortage remain the two main obstacles for expanding the bone marrow transplantation program.
Topics: Allografts; Autografts; Bone Marrow Transplantation; Hemoglobinopathies; Humans; Kuwait; Leukemia; Peripheral Blood Stem Cell Transplantation
PubMed: 28666103
DOI: 10.1016/j.hemonc.2017.05.020 -
Molecular Therapy : the Journal of the... May 2024In recent years, a growing number of clinical trials have been initiated to evaluate gene therapy approaches for the treatment of patients with transfusion-dependent... (Review)
Review
In recent years, a growing number of clinical trials have been initiated to evaluate gene therapy approaches for the treatment of patients with transfusion-dependent β-thalassemia and sickle cell disease (SCD). Therapeutic modalities being assessed in these trials utilize different molecular techniques, including lentiviral vectors to add functional copies of the gene encoding the hemoglobin β subunit in defective cells and CRISPR-Cas9, transcription activator-like effector protein nuclease, and zinc finger nuclease gene editing strategies to either directly address the underlying genetic cause of disease or induce fetal hemoglobin production by gene disruption. Here, we review the mechanisms of action of these various gene addition and gene editing approaches and describe the status of clinical trials designed to evaluate the potentially for these approaches to provide one-time functional cures to patients with transfusion-dependent β-thalassemia and SCD.
Topics: Humans; Genetic Therapy; Gene Editing; CRISPR-Cas Systems; Hemoglobinopathies; Genetic Vectors; Clinical Trials as Topic; Anemia, Sickle Cell; beta-Thalassemia; Animals; Lentivirus
PubMed: 38454604
DOI: 10.1016/j.ymthe.2024.03.005