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British Medical Journal Feb 1972
Review
Topics: Alleles; Anemia, Sickle Cell; Child; Fetal Hemoglobin; Genetic Code; Hemoglobin C Disease; Hemoglobinopathies; Hemoglobins; Hemoglobins, Abnormal; Humans; Infant; Malaria; Prognosis; Protein Conformation; Thalassemia
PubMed: 4550414
DOI: 10.1136/bmj.1.5796.363 -
Saudi Medical Journal Feb 2020To investigate the prevalence and significance of different endocrinopathies in children and adolescents with transfusion-dependent thalassemia and sickle-cell anemia.
OBJECTIVES
To investigate the prevalence and significance of different endocrinopathies in children and adolescents with transfusion-dependent thalassemia and sickle-cell anemia.
METHODS
This is a descriptive, retrospective study between January 2010 and July 2018 in King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Data was collected through reviewing electronic hospital medical records then filling out data collection sheets and was interpreted through the IBM SPSS Statistics for Windows version 20.0 (IBM Corp, Armonk, NY, USA). Results: The total sample size was 119 patients, gender equality was almost achieved with 55.5% being male and 45.5% being female. The most common endocrinopathies were identified in the following order of short stature (39.5%), diabetes mellitus (29.4%), hypogonadism (12.6%), osteopenia (12.6%), osteoporosis (9.2%), hypothyroidism (9.2%), hypocortisolism (3.4%), and hypoparathyroidism (2.5%). All of which were statistically significant in their relationship to hemoglobinopathies with the exception of osteopenia and osteoporosis. Hypogonadism and hypocortisolism were found to be statistically significant in their relationship to a positive history of splenectomy at p=0.026 and p=0.012. Short stature was found to be statistically significant in its relationship to the male gender with a p=0.001. Conclusion: Endocrinopathy is a frequent complication of hemoglobinopathies, for which the most common were found to be short stature, diabetes mellitus, and low bone mineral density.
Topics: Adolescent; Anemia, Sickle Cell; Blood Transfusion; Body Height; Bone Density; Child; Data Analysis; Diabetes Mellitus; Endocrine System Diseases; Female; Hemoglobinopathies; Humans; Male; Prevalence; Retrospective Studies; Saudi Arabia; Thalassemia; Time Factors
PubMed: 32020146
DOI: 10.15537/smj.2020.2.24845 -
Nature Medicine Mar 2015Anemia is a major source of morbidity and mortality worldwide. Here we review recent insights into how red blood cells (RBCs) are produced, the pathogenic mechanisms... (Review)
Review
Anemia is a major source of morbidity and mortality worldwide. Here we review recent insights into how red blood cells (RBCs) are produced, the pathogenic mechanisms underlying various forms of anemia, and novel therapies derived from these findings. It is likely that these new insights, mainly arising from basic scientific studies, will contribute immensely to both the understanding of frequently debilitating forms of anemia and the ability to treat affected patients. Major worldwide diseases that are likely to benefit from new advances include the hemoglobinopathies (β-thalassemia and sickle cell disease); rare genetic disorders of RBC production; and anemias associated with chronic kidney disease, inflammation, and cancer. Promising new approaches to treatment include drugs that target recently defined pathways in RBC production, iron metabolism, and fetal globin-family gene expression, as well as gene therapies that use improved viral vectors and newly developed genome editing technologies.
Topics: Anemia; Fetal Hemoglobin; Genetic Therapy; Hematinics; Hemoglobinopathies; Humans; Inflammation; Neoplasms; Renal Insufficiency, Chronic
PubMed: 25742458
DOI: 10.1038/nm.3814 -
Molecular Therapy : the Journal of the... Mar 2023
Topics: Humans; Gene Editing; Hemoglobinopathies; CRISPR-Cas Systems
PubMed: 36803951
DOI: 10.1016/j.ymthe.2023.02.007 -
Cold Spring Harbor Perspectives in... Feb 2013Over the years, study of the disorders of hemoglobin has served as a paradigm for gaining insights into the cellular and molecular biology, as well as the... (Review)
Review
Over the years, study of the disorders of hemoglobin has served as a paradigm for gaining insights into the cellular and molecular biology, as well as the pathophysiology, of inherited genetic disorders. To date, more than 1000 disorders of hemoglobin synthesis and/or structure have been identified and characterized. Study of these disorders has established the principle of how a mutant genotype can alter the function of the encoded protein, which in turn can lead to a distinct clinical phenotype. Genotype/phenotype correlations have provided important understanding of pathophysiological mechanisms of disease. Before presenting a brief overview of these disorders, we provide a summary of the structure and function of hemoglobin, along with the mechanism of assembly of its subunits, as background for the rationale and basis of the different categories of disorders in the classification.
Topics: Anemia, Sickle Cell; Globins; Hemoglobinopathies; Hemoglobins; Hemoglobins, Abnormal; Humans; Intellectual Disability; Mutation; Myelodysplastic Syndromes; Oxygen; Phenotype; Protein Biosynthesis; Thalassemia
PubMed: 23378597
DOI: 10.1101/cshperspect.a011684 -
Methods in Molecular Biology (Clifton,... 2018Animal models of erythropoiesis have been, and will continue to be, important tools for understanding molecular mechanisms underlying the development of this cell... (Review)
Review
Animal models of erythropoiesis have been, and will continue to be, important tools for understanding molecular mechanisms underlying the development of this cell lineage and the pathophysiology associated with various human erythropoietic diseases. In this regard, the mouse is probably the most valuable animal model available to investigators. The physiology and short gestational period of mice make them ideal for studying developmental processes and modeling human diseases. These attributes, coupled with cutting-edge genetic tools such as transgenesis, gene knockouts, conditional gene knockouts, and genome editing, provide a significant resource to the research community to test a plethora of hypotheses. This review summarizes the mouse models available for studying a wide variety of erythroid-related questions, as well as the properties inherent in each one.
Topics: Animals; Chromosomes, Artificial, Bacterial; Chromosomes, Artificial, Yeast; Disease Models, Animal; Erythropoiesis; Gene Expression Regulation, Developmental; Genes, Reporter; Hemoglobinopathies; Hemoglobins; Mice; Mice, Knockout; Mice, Transgenic
PubMed: 29076083
DOI: 10.1007/978-1-4939-7428-3_3 -
Human Genetics Sep 2016Hemoglobinopathies are genetic disorders caused by aberrant hemoglobin expression or structure changes, resulting in severe mortality and health disparities worldwide.... (Review)
Review
Hemoglobinopathies are genetic disorders caused by aberrant hemoglobin expression or structure changes, resulting in severe mortality and health disparities worldwide. Sickle cell disease (SCD) and β-thalassemia, the most common forms of hemoglobinopathies, are typically treated using transfusions and pharmacological agents. Allogeneic hematopoietic stem cell transplantation is the only curative therapy, but has limited clinical applicability. Although gene therapy approaches have been proposed based on the insertion and forced expression of wild-type or anti-sickling β-globin variants, safety concerns may impede their clinical application. A novel curative approach is nuclease-based gene correction, which involves the application of precision genome-editing tools to correct the disease-causing mutation. This review describes the development and potential application of gene therapy and precision genome-editing approaches for treating SCD and β-thalassemia. The opportunities and challenges in advancing a curative therapy for hemoglobinopathies are also discussed.
Topics: Clinical Trials as Topic; Gene Editing; Genetic Therapy; Hematopoietic Stem Cell Transplantation; Hemoglobinopathies; Humans
PubMed: 27314256
DOI: 10.1007/s00439-016-1696-0 -
Expert Review of Hematology Oct 2021Drug efficacy and toxicity are closely related to the unique genetic profile of individuals, or pharmacogenomics. Despite the fact that cardiology, psychiatry and...
Drug efficacy and toxicity are closely related to the unique genetic profile of individuals, or pharmacogenomics. Despite the fact that cardiology, psychiatry and oncology are among the clinical specialties in which pharmacogenomics has become a clinical reality, the utility of pharmacogenomics has yet to be demonstrated for several other medical specialties. Over the last 15 years, genomic variants in a number of loci have been shown to be significantly associated with the fetal hemoglobin (HbF) response to hydroxyurea, the only approved drug for HbF induction for sickle cell disease. Here, we provide an update and discuss future challenges to the application of pharmacogenomics to improve therapies for β-hemoglobinopathies in relation to the current pharmacological treatment modalities for those disorders.
Topics: Anemia, Sickle Cell; Hemoglobinopathies; Humans; Hydroxyurea; Pharmacogenetics; beta-Thalassemia
PubMed: 34490838
DOI: 10.1080/17474086.2021.1977117 -
Ugeskrift For Laeger Jan 2021The prevalence of people in Denmark descending from areas with a high prevalence of haemoglobinopathies is approximately one tenth and increasing. Since 1995, the Danish... (Review)
Review
The prevalence of people in Denmark descending from areas with a high prevalence of haemoglobinopathies is approximately one tenth and increasing. Since 1995, the Danish Health Authority has recommended haemoglobinopathy screening of pregnant women with ethnic roots outside Northern Europe. Partners of pregnant haemoglobinopathy carriers are also tested. Carrier state in both parents leads to genetic counselling, and prenatal diagnostics of the foetus (chorionic villus biopsy or amniocentesis) is offered, which can lead to abortion and/or preimplantation genetic screening for future pregnancies, as discussed in this review.
Topics: Amniocentesis; Denmark; Europe; Female; Hemoglobinopathies; Humans; Pregnancy; Prenatal Diagnosis
PubMed: 33491643
DOI: No ID Found -
Blood Mar 2021In this issue of , guided by clinical observations and needs, Gong et al have identified a germline missense mutation in DNA methyltransferase 1 (), a ubiquitously...
In this issue of , guided by clinical observations and needs, Gong et al have identified a germline missense mutation in DNA methyltransferase 1 (), a ubiquitously expressed key epigenetic regulator, as a cause of hereditary persistence of fetal hemoglobin (HPFH). HPFH protects against β-thalassemia and sickle cell disease (the β-hemoglobinopathies). Discussed here is how these findings by Gong et al continue the pioneering role of the β-hemoglobinopathies as a model of discovery for all biomedicine. Sickle cell disease, after all, is the “first molecular disease”: altered migration of sickle vs normal hemoglobin in gel electrophoresis demonstrated, for the first time, that the structure–chemical basis for disease is discoverable and knowable.
Topics: Hemoglobinopathies; Humans; beta-Globins
PubMed: 33764430
DOI: 10.1182/blood.2020009961