Generation of an EYS-associated retinitis pigmentosa patient-derived human pluripotent stem cell line (MUi038-A).

Mutations in the eyes shut homolog (EYS) gene are one of the common causes of autosomal recessive retinitis pigmentosa (RP). The lack of suitable animal models hampers progress understanding of the disease mechanism and drug development. This study reported the reprogramming of CD34+ hematopoietic stem/progenitor cells from a patient with compound heterozygous EYS mutations (c.

miR-214 aggravates oxidative stress in thalassemic erythroid cells by targeting ATF4.

Oxidative damage to erythroid cells plays a key role in the pathogenesis of thalassemia. The oxidative stress in thalassemia is potentiated by heme, nonheme iron, and free iron produced by the Fenton reaction, due to degradation of the unstable hemoglobin and iron overload. In addition, the levels of antioxidant enzymes and molecules are significantly decreased in erythrocytes in α- and β-thalassemia.

Proteomic profiling of circulating β-thalassaemia/haemoglobin E extra-cellular vesicles reveals that association with immunoglobulin induces membrane vesiculation.

Splenectomised β-thalassaemia/haemoglobin E (HbE) patients have increased levels of circulating microparticles or medium extra-cellular vesicles (mEVs). The splenectomised mEVs play important roles in thromboembolic complications in patients since they can induce platelet activation and endothelial cell dysfunction. However, a comprehensive understanding of the mechanism of mEV generation in thalassaemia disease has still not been reached.

Generation of human induced pluripotent stem cell line (MUi033-A) from a male with homozygous for Hemoglobin E.

Hemoglobin E (HbE), a common variant in Southeast Asian populations, results from a G to A substitution at codon 26 of the HBB gene, causing abnormal Hb and mild β-thalassemia-like symptoms. Here, we derived an induced pluripotent stem cell (iPSC) line, named MUi033-A, from a male homozygous for HbE. The iPSC line demonstrates a normal karyotype and embryonic stem cell-like properties including pluripotency gene expression, and tri-lineage differentiation potential.

Development of molecular diagnostic platform for α -thalassemia 44.6 kb (Chiang Rai, -- ) deletion in individuals with microcytic red blood cells across Thailand.

Introduction: The α -thalassemia 44.6 kb or Chiang Rai (-- ) deletion has been reported in northern Thailand and is capable of causing hemoglobin (Hb) H disease and a lethal α-thalassemia genotype, Hb Bart's hydrops fetalis, in this region. However, there are no current data regarding the frequency of -- nationwide due to a lack of effective diagnostic assay.

Generation of human induced pluripotent stem cell line (MUi034-A) from an unusual case of hydrops fetalis associated with homozygous hemoglobin Constant Spring.

Hemoglobin Constant Spring (HbCS) is unstable hemoglobin resulting from a nucleotide substitution at the termination codon of the HBA2 gene (c.427 T > C). The homozygous state for HbCS is non-transfusion dependent in adults.

A generation of human-induced pluripotent stem cell line (MUi032-A) from a Choroideremia disease patient carrying a hemizygous mutation on the CHM gene.

Choroideremia (CHM) is a monogenic, X-linked inherited retinal disease caused by mutations in the CHM gene. CHM patients develop progressive loss of vision due to degeneration of cell layers in the retina. In this report, the human-induced pluripotent stem cell, MUi032-A, was generated from CD34+ hematopoietic stem/progenitor cells of a male CHM patient by co-electroporation of non-integration episomal vectors containing OCT4/shp53, Sox-2/KLF4, and L-MYC/LIN-28.

A comprehensive study of immune function and immunophenotyping of white blood cells from β-thalassaemia/HbE patients on hydroxyurea supports the safety of the drug.

Hydroxyurea (HU) (hydroxycarbamide) is used as a therapeutic option in β-thalassaemia to increase fetal haemoglobin, which results in a reduced requirement for blood transfusion. However, a potential serious adverse effect of HU is neutropenia. Abnormal neutrophil maturation and function in β-thalassaemia/HbE patients are well documented.

Kinetics of lipid radical formation in lipoproteins from β-thalassemia: Implication of cholesteryl esters and α-tocopherol.

Vascular complications in β-thalassemia are associated with oxidative modification of lipoproteins under high oxidative stress. The lipid components of lipoproteins are oxidized via lipid peroxidation and produce lipid radicals (L•) as the key initial intermediates. Modification of lipid components, therefore, might result in alterations in the rate and products of lipid peroxidation.

Thalassemia in Thailand.

Thailand has a population of 66.2 million with 30.0-40.

Clinical Severity of β-Thalassemia Pediatric Patients in Myanmar.

β-Thalassemia (β-thal) is highly prevalent in Myanmar, but limited data are available on the molecular basis and the clinical manifestations in Myanmar patients. In this study, we investigated the clinical features and β-globin gene abnormalities in 15 homozygous β-thal and 60 Hb E (: c.79G>A)/β-thal pediatric patients who attended Yangon Children Hospital, the biggest thalassemia day care unit center in Myanmar.

Impaired neutrophil extracellular trap formation in β-thalassaemia/HbE.

Neutrophil dysfunction contributes to a high susceptibility to severe bacterial infection which is a leading cause of morbidity and mortality in β-thalassaemia/HbE, especially in splenectomised patients. This study demonstrated another abnormality of neutrophil function, namely neutrophil extracellular trap (NET) formation in splenectomised and non-splenectomised β-thalassaemia/HbE patients who had iron overload. A classification system of morphological NET formation using confocal microscopy was developed, and samples were categorized into early and late phases which were subdivided into web-like and non-web structures.

Iron chelation therapy with deferiprone improves oxidative status and red blood cell quality and reduces redox-active iron in β-thalassemia/hemoglobin E patients.

The oxidative status of twenty-three β-thalassemia/hemoglobin E patients was evaluated after administration of 75 mg/kg deferiprone (GPO-L-ONE®) divided into 3 doses daily for 12 months. Serum ferritin was significantly decreased; the median value at the initial and final assessments was 2842 and 1719 ng/mL, respectively. Progressive improvement with significant changes in antioxidant enzyme activity, including plasma paraoxonase (PON) and platelet-activating factor acetylhydrolase (PAF-AH), and in antioxidant enzymes in red blood cells (glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD)) were observed at 3-6 months of treatment.

Development of DNA controls for detection of β-thalassemia mutations commonly found in Asian.

Introduction: Several DNA-based approaches including a reverse dot-blot hybridization (RDB) have been established for detection of β-thalassemia genotypes to provide accurate genetic counseling and prenatal diagnosis for prevention and control of severe β-thalassemia. However, one of major concerns of these techniques is a risk of misdiagnosis due to a lack of DNA controls. Here, we constructed positive DNA controls for β-thalassemia genotyping in order to ensure that all steps in the analysis are performed properly.

Update in Laboratory Diagnosis of Thalassemia.

Alpha- and β-thalassemias and abnormal hemoglobin (Hb) are common in tropical countries. These abnormal globin genes in different combinations lead to many thalassemic diseases including three severe thalassemia diseases, i.e.

UNC0638 induces high levels of fetal hemoglobin expression in β-thalassemia/HbE erythroid progenitor cells.

Increased expression of fetal hemoglobin (HbF) improves the clinical severity of β-thalassemia patients. EHMT1/2 histone methyltransferases are epigenetic modifying enzymes that are responsible for catalyzing addition of the repressive histone mark H3K9me2 at silenced genes, including the γ-globin genes. UNC0638, a chemical inhibitor of EHMT1/2, has been shown to induce HbF expression in human erythroid progenitor cell cultures.

Hemoglobin-bound platelets correlate with the increased platelet activity in hemoglobin E/β-thalassemia.

Introduction: An increase in platelet activity is a contributing factor to vascular complications in hemoglobin E/β-thalassemia (HbE/β-thal). Plasma-free hemoglobin (Hb) increases in HbE/β-thal patients and correlates with platelet activation, but the levels of Hb-bound platelets have never been reported. In this study, we aimed to investigate the levels of Hb-bound platelets and its association with platelet activity in HbE/β-thal patients.

Impact of the detection of ζ-globin chains and hemoglobin Bart's using immunochromatographic strip tests for α0-thalassemia (--SEA) differential diagnosis.

α0-Thalassemia is an inherited hematological disorder caused by the deletion of α-globin genes. The Southeast Asian deletion (--SEA) is the most common type of α0-thalassemia observed in Southeast Asian countries. Regarding WHO health policy, an effective α0-thalassemia screening strategy is needed to control new severe α-thalassemia cases.