- In Vivo Molecular Profiling of Human Glioma : Cross-Sectional Observational Study Using Dynamic Susceptibility Contrast Magnetic Resonance Perfusion Imaging. [Journal Article]
- CNClin Neuroradiol 2018 Feb 21
- CONCLUSIONS: The DSC-MRI procedure may provide insight into the IDH1/2 mutation and ATRX expression status and MGMT methylation profile of diffuse glioma; however, taking integrated oligodendroglioma into account limits the diagnostic performance of rCBV in non-invasively predicting the molecular subtype.
- Molecular Characteristics of Hb New York [β113(G15)Val→Glu, HBB: c.341T>A] in Thailand. [Journal Article]
- HHemoglobin 2018 Feb 21; :1-5
- Hb New York or Hb Kaohsiung [β113(G15)Val→Glu (GTG>GAG), HBB: c.341T>A] has been considered a rare β hemoglobin (Hb) variant found originally in an Iranian woman and later in diverse populations but ...
Hb New York or Hb Kaohsiung [β113(G15)Val→Glu (GTG>GAG), HBB: c.341T>A] has been considered a rare β hemoglobin (Hb) variant found originally in an Iranian woman and later in diverse populations but its genetic origin has not been elucidated. Here we report molecular and hematological descriptions of this variant found in the Thai population. Among 5643 subjects referred for hemoglobinopathy investigation during January 2015 to September 2017, 183 (3.2%) were found to carry several Hb variants, including β chain variants (n = 135, 2.4%), α chain variants (n = 33, 0.6%), Hb Lepore-Hollandia (NG_000007.3: g.63290_70702del) and Hb Lepore-Boston-Washington (NG_000007.3: g.63632_71046del) (δβ hybrid Hb) (n = 12, 0.2%) and δ chain variants (n = 3, 0.05%). Of patients with β chain variants, six with normal high performance liquid chromatography (HPLC) patterns, had an abnormal Hb in zone 11 of capillary electrophoresis (CE), the amounts of which ranged from 29.6-45.4% with normal levels of Hb A2and Hb F. DNA analysis identified a heterozygous Hb New York mutation in all cases. Further screening of α-thalassemia (α-thal) identified coinheritance of α+- and α0-thal in two of them who had reduced levels of Hb New York. Haplotype analysis suggested that the Thai Hb New York was likely associated with a single β-globin haplotype [+ - - - - + +], indicating that it was of the same origin. Hematological findings and simple DNA assay based on allele-specific polymerase chain reaction (PCR) for rapid detection of Hb New York are presented.
- Ineffective Erythropoiesis: Anemia and Iron Overload. [Review]
- HOHematol Oncol Clin North Am 2018; 32(2):213-221
- Stress erythropoiesis (SE) is characterized by an imbalance in erythroid proliferation and differentiation under increased demands of erythrocyte generation and tissue oxygenation. β-thalassemia repr...
Stress erythropoiesis (SE) is characterized by an imbalance in erythroid proliferation and differentiation under increased demands of erythrocyte generation and tissue oxygenation. β-thalassemia represents a chronic state of SE, called ineffective erythropoiesis (IE), exhibiting an expansion of erythroid-progenitor pool and deposition of alpha chains on erythrocyte membranes, causing cell death and anemia. Concurrently, there is a decrease in hepcidin expression and a subsequent state of iron overload. There are substantial investigative efforts to target increased iron absorption under IE. There are also avenues for targeting cell contact and signaling within erythroblastic islands under SE, for therapeutic benefits.
- Clinical Classification, Screening and Diagnosis for Thalassemia. [Review]
- HOHematol Oncol Clin North Am 2018; 32(2):193-211
- At present, thalassemia diseases are classified into transfusion-dependent thalassemia and non-transfusion-dependent thalassemia. This classification is based on the clinical severity of patients det...
At present, thalassemia diseases are classified into transfusion-dependent thalassemia and non-transfusion-dependent thalassemia. This classification is based on the clinical severity of patients determining whether they do require regular blood transfusions to survive (transfusion-dependent thalassemia) or not (non-transfusion-dependent thalassemia). In addition to the previous terminology of "thalassemia major" or "thalassemia intermedia," this classification has embraced all other forms of thalassemia syndromes such as α-thalassemia, hemoglobin E/β-thalassemia and combined α- and β-thalassemias. Definitive diagnosis of thalassemia and hemoglobinopathies requires a comprehensive workup from complete blood count, hemoglobin analysis, and molecular studies to identify mutations of globin genes.
- Molecular Basis and Genetic Modifiers of Thalassemia. [Review]
- HOHematol Oncol Clin North Am 2018; 32(2):177-191
- Thalassemia is a disorder of hemoglobin characterized by reduced or absent production of one of the globin chains in human red blood cells with relative excess of the other. Impaired synthesis of β-g...
Thalassemia is a disorder of hemoglobin characterized by reduced or absent production of one of the globin chains in human red blood cells with relative excess of the other. Impaired synthesis of β-globin results in β-thalassemia, whereas defective synthesis of α-globin leads to α-thalassemia. Despite being a monogenic disorder, thalassemia exhibits remarkable clinical heterogeneity that is directly related to the intracellular imbalance between α- and β-like globin chains. Novel insights into the genetic modifiers have contributed to the understanding of the correlation between genotype and phenotype and are being explored as therapeutic pathways to cure this life-limiting disease.
- Quantitative Trait Loci Influencing Hb F Levels in Southern Thai Hb E (HBB: c.79G>A) Heterozygotes. [Journal Article]
- HHemoglobin 2018 Feb 19; :1-7
- Variation of fetal hemoglobin (Hb F) expression in heterozygous Hb E (HBB: c.79G>A) individuals is associated with several genetic modifiers and not well understood. This study was undertaken in orde...
Variation of fetal hemoglobin (Hb F) expression in heterozygous Hb E (HBB: c.79G>A) individuals is associated with several genetic modifiers and not well understood. This study was undertaken in order to determine the effect of single nucleotide polymorphisms (SNPs), including XmnIGγ (rs7482144), rs766432 on the BCL11A gene and rs9376074 on the HBS1L gene, on Hb F levels in Southern Thai heterozygous Hb E individuals. A total of 97 Southern Thai subjects carrying heterozygous Hb E were selected for the hematological study. After excluding the samples with α-thalassemia (α-thal) interaction or moderate anemia, because both conditions can affect the hematological parameters, the remaining 74 samples were submitted to SNP analysis. Hematological parameters were measured using an automated hematology analyzer and high performance liquid chromatography (HPLC). The results show that rs766432 was strongly associated with increased Hb F levels and rs7482144 was associated with Hb F levels in each subgroup (genotype) of rs766432. This study suggested that the BCL11A locus has a major effect on Hb F levels compared with the XmnI polymorphism in Hb E heterozygotes. This association of Hb F levels with SNPs is useful for the interpretation of hemoglobin (Hb) typing in heterozygous Hb E samples with high Hb F levels. Future research will need to address the better understanding of the mechanisms of the SNPs that regulate Hb F production without stress erythropoiesis in Hb E heterozygotes.
- Association between Oxidative Stress, Genetic Factors, and Clinical Severity in Children with Sickle Cell Anemia. [Journal Article]
- JPedJ Pediatr 2018 Feb 13
- CONCLUSIONS: Mild hemolysis in children with alpha-thalassemia may limit oxidative stress and could explain the protective role of alpha-thalassemia in hemolysis-related sickle cell complications.
- Identification of Three Types of α-Thalassemia Deletion, -α21.9, -α2.4, and - -THAI, and Their Frequencies, in One Family in the Population of Southern Guangxi Zhuang Autonomous Region, People's Republic of China. [Journal Article]
- HHemoglobin 2018 Feb 15; :1-6
- Different types of deletional α-thalassemia (α-thal) have been reported by researchers in China. This study describes one family carrying -α21.9(NG_000006.1: g.14373_36299delinsGGGAAGGGTGGGTGGGAATAAC...
Different types of deletional α-thalassemia (α-thal) have been reported by researchers in China. This study describes one family carrying -α21.9(NG_000006.1: g.14373_36299delinsGGGAAGGGTGGGTGGGAATAACAGCTTTT), -α2.4(NG_000006.1: g.36860_39251del) and - -THAI(Thailand) (NG_000006.1: g.10664_44164del) alleles in Guangxi Zhuang Autonomous Region, People's Republic of China (PRC), and reports the frequencies of these types in the population of this region. The proband was a 4-year-old girl, who screened positive for thalassemia, although the thalassemia genotype results were normal when screened using the routine kits. Samples of the proband's parents were also collected to perform further analyses. Two real-time gap-polymerase chain reaction (gap-PCR) systems were designed for separate detection of - -THAIand screening for -α21.9and -α2.4. The genotype of the proband was -α21.9/-α2.4, and the two variants were inherited from her parents. In the frequency study, five - -THAI, four -α21.9and 11 -α2.4positive individuals were detected in the 3410 random samples. Thus, allele frequencies of -α21.9, - -THAIand -α2.4in the population of southern Guangxi were determined as 0.059, 0.073 and 0.161%, respectively. This is the first report of an individual carrying the -α21.9/-α2.4genotype, and the first report of the detection of -α21.9, -α2.4and - -THAIin a single family. The total frequency for these alleles was 0.293% in southern Guangxi, suggesting that the thalassemia clinical center in this region should utilize a screening kit that allows detection of these types of deletions for a more comprehensive evaluation of thalassemia risk.
- No Association of Genetic Markers with Carotid Intimal Medial Thickness in β-Thalassemia Major Patients. [Journal Article]
- JPJ Pediatr Genet 2018; 7(1):19-22
- Regular transfusion leads to cardiac siderosis resulting in cardiac complications that account for more than 71% of the total mortality in thalassemia patients. We aimed to study the variants of matr...
Regular transfusion leads to cardiac siderosis resulting in cardiac complications that account for more than 71% of the total mortality in thalassemia patients. We aimed to study the variants of matrix metalloproteinase-9 (MMP9), matrix Gla protein (MGP), and estrogen receptor α(ERα), which might be contributing to atherosclerosis, leading to heart failure in thalassemia major. One hundred and five thalassemia patients on regular transfusion and iron chelation therapy were enrolled for the study. Carotid artery intimal medial thickness (CIMT) measurement was done to check for atherosclerosis.MMP9 (C1562T),MGP(T138C), andERα gene (PvuII (rs2234693T > C) andXbaI (rs9340799A > G) polymorphism were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. CIMT values were within the normal range (<0.90 mm) in all patients. There was no difference in mean CIMT values between males and females (0.56 ± 0.11 versus 0.56 ± 0.12,p = 0.928). There was no correlation of CIMT with age, body surface area, and body mass index as well as with serum ferritin levels. No statistically significant difference in frequency of MMP9, MGP, and ERα genotypes was seen in two dichotomized groups of CIMT (CIMT < 0.56 and CIMT ≥ 0.56). Variants ofMMP9,MGP, and ERα have a reserved influence on cardiac disease pathogenesis, and the disease phenotype in thalassemia patients may be more strongly impacted by other factors.
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- α-thalassaemia combined with hereditary spherocytosis in the same patient. [Journal Article]
- ETExp Ther Med 2018; 15(2):1298-1303
- A family of four from the Guangxi Zhuang Autonomous Region of China, including a child with α-thalassaemia and hereditary spherocytosis (HS), underwent laboratory identification, and genetic analysis...
A family of four from the Guangxi Zhuang Autonomous Region of China, including a child with α-thalassaemia and hereditary spherocytosis (HS), underwent laboratory identification, and genetic analysis. After harvesting peripheral blood samples from the child patient and his family members, GAP-polymerase chain reaction (PCR) and reverse dot-blot tests were used to identify thalassaemia genotypes. After amplifying exons and the adjacent introns of solute carrier family 4 member 1 (Diego blood group) (SLC4A1), ankyrin 1, spectrin α erythrocytic 1, spectrin β erythrocytic and erythrocyte membrane protein band 4.2 by PCR, DNA sequencing was utilised to detect gene mutations of HS. The thalassaemia gene of the child patient was -α3.7/αα and identical to the genotype of his mother. DNA testing of HS identified two mutation sites on the SLC4A1 gene: Exon 3 c.113A>C (Asp 38 Ala) and intron 7 c.609+86G>A. The father and older sister of the patient also had the same mutations. Due to the mutual interference with disorders of haemoglobin synthesis and erythrocyte membrane defects of laboratory results, it is difficult to diagnose HS when it coexists with thalassaemia. When clinical manifestations and laboratory results cannot be explained by a single haemolytic anaemia, the possibility of combining with another haemolytic anaemia should be considered. Thus, it is necessary to perform pedigree investigation and genetic analyses for a final diagnosis.