Molecular Understanding of Non-Transfusion-Dependent Thalassemia Associated with Hemoglobin E-β-Thalassemia in Northeast Thailand

2016 ◽  
Vol 136 (4) ◽  
pp. 233-239 ◽  
Author(s):  
Supawadee Yamsri ◽  
Naruwat Pakdee ◽  
Goonnapa Fucharoen ◽  
Kanokwan Sanchaisuriya ◽  
Supan Fucharoen
Keyword(s):  
Molecular Basis ◽  
Hematological Parameters ◽  
Globin Gene ◽  
Gene Mutations ◽  
Nucleotide Polymorphisms ◽  
Genetic Modifiers ◽  
Northeast Thailand ◽  
Hemoglobin E ◽  
Myb Gene ◽  
Significant Difference

Non-transfusion-dependent thalassemia (NTDT) is associated with various forms of thalassemia and genetic modifiers. We report the molecular basis of NTDT in hemoglobin (Hb) E-β-thalassemia disease. This study was done in 73 adult patients encountered at the prenatal diagnosis center of Khon Kaen University, Northeast Thailand. Hematological parameters and Hb patterns were collected, and α- and β-globin gene mutations were determined. Multiple single-nucleotide polymorphisms (SNPs) including the rs7482144/Gγ-XmnI polymorphism, rs2297339, rs2838513, rs4895441, and rs9399137 in the HBS1L-MYB gene, rs4671393 and rs11886868 in the BCL11A gene, and G176AfsX179 in the KLF1 gene were examined. Five β0-thalassemia mutations and a severe β+-thalassemia mutation in trans to the βE gene were identified. No significant difference in hematological parameters was observed among β-thalassemia genotypes. Coinheritance of α-thalassemia was observed in 31 of the 73 subjects (42.5%). Four SNPs including Gγ-XmnI, rs2297339, rs4895441, and rs9399137 of HBS1L-MYB were found to be associated with high Hb F levels in 39 (53.4%) subjects. The molecular basis of NTDT in the remaining 3 (4.1%) cases could not be defined. These results indicate multiple genetic factors in NTDT patients and underline the importance of complete genotyping to provide proper management, make clinical predictions, and improve genetic counseling.

scholarly journals MOLECULAR ANALYSIS OF NON-TRANSFUSION DEPENDENT THALASSEMIA ASSOCIATED WITH HEMOGLOBIN E-β-THALASSEMIA DISEASE WITHOUT α--THALASSEMIA

2019 ◽  
Vol 11 (1) ◽  
pp. e2019038 ◽  
Author(s):  
Paramee Phanrahan ◽  
Supawadee Yamsri ◽  
Nattiya Teawtrakul ◽  
Goonnapa Fucharoen ◽  
Kanokwan Sanchaisuriya ◽  
...  
Keyword(s):  
Dna Analysis ◽  
Globin Gene ◽  
Phenotypic Expression ◽  
Nucleotide Polymorphisms ◽  
Thalassemia Patient ◽  
Hemoglobin E ◽  
Modifying Factors ◽  
Myb Gene ◽  
Hb E ◽  
Klf1 Gene

Background: The finding of many Thai Hb E-β0-thalassemia patients with non-transfusion dependent thalassemia (NTDT) phenotype without co-inheritance of α-thalassemia has prompted us to investigate the existence of other genetic modifying factors. Methods: Study was done on 146 adult Thai patients with NTDT Hb E-β0-thalassemia and a homozygous β-thalassemia patient without co-inheritance of α-thalassemia. Multiple single-nucleotide polymorphisms (SNPs) associated with γ-globin gene expression including the Gγ-XmnI of HBG2 gene, rs2297339, rs4895441, and rs9399137 of the HBS1L-MYB gene, rs4671393 in the BCL11A gene, and G176AfsX179, T334R, R238H and -154 (C-T) in the KLF1 gene were investigated using PCR-and related techniques. Results: Heterozygous and homozygous for Gg-XmnI of HBG2 gene were detected at 68.0% and 6.1%, respectively. Further DNA analysis identified the rs2297339 (C-T), rs4895441 (A-G), and rs9399137 (T-C) of HBS1L-MYB gene in 86.4%, 22.5% and 20.4%, respectively. The rs4671393 (G-A) of the BCL11A gene was found at 31.3%. For the KLF1 gene, the T334R and G176AfsX179 (+/-) were detected at 8.2% and 1.4%, respectively. Conclusion: It was found that these SNPs when analyzed in combination could explain the mild phenotypic expression of all cases. These results underline the importance of these informative SNPs on phenotypic expression of Hb E-β-thalassemia patients.

scholarly journals Beta-Thalassemia Intermedia: A Single Thalassemia Center Experience from Northeastern Iraq

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Shaema Salih Amin ◽  
Sana Dlawar Jalal ◽  
Kosar Muhammed Ali ◽  
Ali Ibrahim Mohammed ◽  
Luqman Khalid Rasool ◽  
...  
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
Beta Thalassemia ◽  
Abnormal Liver Function Test ◽  
Hybridization Technique ◽  
Genetic Modifiers ◽  
Thalassemia Intermedia ◽  
Female Sex ◽  
Increased Risk ◽  
Thalassemia Mutation

Objective. To determine the molecular characterization and disease-associated complications of beta-thalassemia intermedia (β-TI) patients in Sulaymaniyah province, northeastern Iraq. Methods. A total of 159 β-TI patients from 114 families were enrolled. Detection of β-thalassemia mutations was done by reverse hybridization technique and direct gene sequencing. Also, the clinical and hematological data were collected through an electronic-based medical recording system using a designed comprehensive questionnaire. Results. Nineteen different β-globin gene mutations arranged in 37 various genotypes were determined. The most frequent were IVS-II-I (G>A) (47.2%), followed by IVS-I-6 (T>C) (23.3%) and IVS-I-110 (G>A) (5%). Among disease-related morbidities documented, bone disease amounted to 53% (facial deformity and osteoporosis), followed by endocrinopathies 17.6% (growth retardation and subclinical hypothyroidism), cholelithiasis 13.8%, pulmonary hypertension 11.3%, and abnormal liver function test 7.5%, whereas venous thrombosis, extramedullary hemopoiesis, and leg ulcer were less frequently observed. Age≥35 and female sex were risk factors for cholelithiasis, while age was an independent risk for hypothyroidism and female sex was associated with increased risk for osteoporosis. Mean serum ferritin of ≥1000 μg/L was associated with an increased risk of osteoporosis, whereas chelation therapy was protective for a multitude of other complications. Transfusion, on the other hand, increased the risk of osteoporosis, yet it was protective for cholelithiasis and hypothyroidism. Moreover, splenectomy was protective for cholelithiasis, although it was an independent risk for hypothyroidism. Finally, hydroxyurea was associated with an increased risk of osteoporosis, while it was protective for cholelithiasis. Discussion and Conclusion. β+-thalassemia mutation had contributed to 41.25 of families with a less severe β-thalassemia phenotype in the northeastern part of Iraq, justifying the need to investigate the contribution of genetic modifiers in ameliorating disease severity. In addition, the substantial number of β-TI patients developed disease-related morbidities, which necessitates the need for more appropriate clinical management with earlier intervention.

Searching for Disease Modifiers Genes in Thalassemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3642-3642
Author(s):  
Suthat Fucharoen ◽  
Orapan Sripichai ◽  
Pranee Winichagoon ◽  
Kenneth Abel ◽  
Andreas Braun
Keyword(s):  
Disease Severity ◽  
Dna Analysis ◽  
Genome Wide Association Study ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Nucleotide Polymorphisms ◽  
Genetic Modifiers ◽  
Chromosome 11 ◽  
Genotype Frequencies ◽  
A Genome

Abstract β0-thalassemia/HbE disease is one of the most common thalassemias in Southeast Asia. Patients with compound heterozygote for HbE and β0 mutant alleles display remarkable variability in clinical expression, ranging from nearly asymptomatic to severe, transfusion-dependent disease. It is believed that additional genetic factors modifying disease severity may account for this variability. A universal platform technology (MassARRAY) based on mass spectrometry for analyzing nucleic acids at a high level of precision and accuracy has been developed. To identify genetic modifiers influencing severity among 1060 β0-thalassemia/HbE patients, we are utilizing this technology to conduct a genome-wide association study involving approximately 110,000 gene-based single nucleotide polymorphisms (SNPs). This assay panel corresponds to SNPs with a median spacing of 10.4 kilobases, in approximately 99% of all known and predicted human genes. DNAs from approximately 200 regionally matched patients representing the extremes of mild and severe cases were included in each DNA pool. Allele frequencies for all SNPs were estimated in both pools, and those showing suggestive significant differences (p values <0.02) were selected for verification by repeated pooled DNA analysis. Approximately one-fourth of these showed reproducible allelic differences at p<0.05, and more than 600 were selected for genotyping the individual patient DNAs in order to determine precise allele and genotype frequencies. A number of SNPs showed evidence for association with disease severity, including several in reported quantitative trait loci (QTLs) associated with fetal hemoglobin HbF levels. However the most strongly associated SNPs were within a region on chromosome 11 distinct from the beta globin gene cluster, within which most analysis to date has focused.

Status research Thalassemia carier among children of ethnic Tay, Dao in Tuyen Quang province

2021 ◽  
Vol 05 (03) ◽  
pp. 102-109
Author(s):  
Thi Thu Giang Do ◽  
◽  
Quang Thanh Pham ◽  
Phuong Thuy Ho
Keyword(s):  
Ethnic Minority ◽  
Dna Analysis ◽  
Single Gene ◽  
Hematological Parameters ◽  
Globin Gene ◽  
Gene Mutations ◽  
Screening Tests ◽  
Minority Children ◽  
Alpha Globin ◽  
Ethnic Minority Children

Objectives: To determine the prevalence of thalassemia carrier, genotype and hematological parameters among children bearing the thalassemia gene in Tuyen Quang. Methodology: A descriptive study was conducted from January to March 2017. 505 ethnic minority children in 6 districts and Tuyen Quang City, Tuyen Quang province were registered voluntarily by the family in the study. MCV index <80fL combined with the DCIP test were used for screening thalassemia and HbE. Hemoglobin electrophoresis and DNA analysis of mutations in the globin alpha gene was performed for all cases positive with screening tests. Results: The prevalence of thalassemia common for ethnic minority children in Tuyen Quang was 28,1%. Four types of single-gene mutations in the alpha globin gene were identified, following types --SEA, -α3.7; -αCS; -α4.2. Conclusion: The general prevalence of thalassemia gene among the Tay and Dao children in Tuyen Quang is 28.1%. Six phenotypic groups carrying thalassemia gene were detected with 10 mutant genotypes. Mutation - SEA accounts for the highest proportion of single allele mutations (72.09%). Keywords: Thalassemia carrier, children, ethnic Tay, ethnic Dao, Tuyen Quang

Phenotype and Genotype in a Cohort of 312 Adult Patients with Nontransfusion-Dependent Thalassemia in Northeast Thailand

2015 ◽  
Vol 135 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Patcharawadee Prayalaw ◽  
Nattiya Teawtrakul ◽  
Arunee Jetsrisuparb ◽  
Saranya Pongudom ◽  
Goonnapa Fucharoen ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Hematological Parameters ◽  
Globin Gene ◽  
Adult Patients ◽  
Molecular Heterogeneity ◽  
Northeast Thailand ◽  
Management Planning ◽  
Dna Analyses ◽  
Hb E ◽  
Xmni Polymorphism

Patients with nontransfusion-dependent thalassemia (NTDT) do not require regular blood transfusion for survival but may encounter several complications that contribute to morbidity and mortality. We report the molecular heterogeneity and hematological features of NTDT in 312 adult patients in northeast Thailand. Hemoglobin (Hb) and DNA analyses identified 177 subjects with Hb E-β-thalassemia, 1 with homozygous β⁰-thalassemia and 134 with Hb H, AEBart's and EEBart's diseases. For β-thalassemia, 12 different mutations including both β⁰- and β+-thalassemias were detected. Coinheritance of α-thalassemia as an ameliorating factor was observed in 18 of 178 cases (10.1%) with β-thalassemia. The α-globin gene triplicated haplotype (αααanti3.7) was observed in 1 case of Hb E-β⁰-thalassemia. The presence of the -158 (C→T) Gγ-XmnI polymorphism (+/+) was found to be associated with increased Hb F expression, but its frequency in the studied subjects was low. Those with α-thalassemia included 17 with deletional and 51 nondeletional Hb H, and 63 with AEBart's and 3 with EEBart's diseases. The hematological parameters of these NTDT and genotype-phenotype relationships are presented. The diverse molecular heterogeneity of NTDT underlines the importance of complete genotyping of the patient. These results should prove useful for management planning, the prediction of clinical outcome and to improve genetic counseling for NTDT patients.

Hemoglobin E and codon 17 nonsense: Two β-globin gene mutations common in Southeast Asia detected by the use of ARMS

1993 ◽  
Vol 67 (3) ◽  
pp. 119-120 ◽  
Author(s):  
H. Steger ◽  
A. Eigel ◽  
G. Flatz ◽  
J. Horst
Keyword(s):  
Southeast Asia ◽  
Globin Gene ◽  
Gene Mutations ◽  
Hemoglobin E

scholarly journals Genotyping of BCL11A and HBS1L-MYB Single Nucleotide Polymorphisms in β-thalassemia/HbE and Homozygous HbE Subjects with Low and High Levels of HbF

2017 ◽  
Vol 15 (9) ◽  
pp. 627-636
Author(s):  
Watcharee PRASING ◽  
Chadia MEKKI ◽  
Patrinee TRAISATHIT ◽  
Serge PISSARD ◽  
Sakorn PORNPRASERT
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
High Performance ◽  
Hematological Parameters ◽  
Hematological Parameter ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Myb Gene ◽  
Genotype Frequencies ◽  
Hbf Level ◽  
Myb Genes

Whether multiple single nucleotide polymorphisms (SNPs) of BCL11A and HBS1L-MYB genes affect hemoglobin (Hb)F production and hematological parameter variation in β-thalassemia/HbE and homozygous HbE in Thai subjects with low and high HbF levels are still unclear. Three SNPs of BCL11A gene (rs1427407, rs10189857 and rs11886868) and 3 SNPs of HBS1L-MYB gene (rs4895441, rs9399137 and rs28384513) were analyzed in 45 β-thalassemia/HbE patients who had HbF levels lower and higher than 15 %, and in 50 homozygous HbE who had HbF levels lower and higher than 5 %. Their hematological parameters were measured using automated blood counter. The HbF level was analyzed using high performance liquid chromatography (HPLC). There were no statistical significant differences of allele and genotype frequencies of 3 SNPs in the BCL11A gene between the groups of β-thalassemia/HbE patients and homozygous HbE subjects with low and high HbF levels. Significant differences in the allele frequencies in HBS1L-MYB SNP rs4895441 (p = 0.041) and rs9399137 (p = 0.048) were observed in homozygous HbE subjects with HbF £ 5 % and > 5 %. Moreover, significant differences in MCV (p = 0.005) and trends towards significant differences in MCH (p = 0.057) and HbF levels (p = 0.051) were found in HBS1L-MYB SNP rs9399137 of homozygous HbE subjects. Therefore, the HBS11L-MYB SNPs especially rs9399137 had an effect on HbF production and the variation of hematological parameters in homozygous HbE subjects, but not in β-thalassemia/HbE patients.

Significance of genetic counseling and prenatal diagnosis on α2 codon 30 (-GAG) (HBA2: c.91_93delGAG) mutation

2019 ◽  
Author(s):  
Zhiyang Guan ◽  
Zeyan Zhong ◽  
Hailin He ◽  
Dan Chen ◽  
Guoxing Zhong ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Prenatal Diagnosis ◽  
Dna Analysis ◽  
Globin Gene ◽  
Gene Mutations ◽  
Severe Form ◽  
Clinical Severity ◽  
Globin Genes ◽  
Significant Difference ◽  
Hb H Disease

Abstract Background : Non-deletional hemoglobin (Hb) H disease is the severest form of α- thalassemia ( thal ) compatible with post-natal life, which is caused by the interaction of an α-globin gene mutation with α 0 -thal. Therefore, it is important to identify rare α-globin gene mutations for the prevention of severe form of non-deletional Hb H disease . Methods: In all, 61,796 samples were characterized at our center. Common α- and β- thalassemia mutations were detected by routine DNA analysis (gap-PCR and PCR-RDB ). The DNA sequencing of α-globin genes was performed to identify the unknown mutation. Statistical analyses were conducted using SPSS 19.0 statistical software. Results: Of the 61,796 samples, eight were identified as α2 codon 30 (-GAG) ( HBA2 : c.91_93delGAG) mutation s, and of these, four had coinheritance with - - SEA deletion Patients with the heterozygous α2 codon 30 (-GAG) ( HBA2 : c.91_93delGAG) mutation had significantly lower levels of MCV and MCH than healthy individuals ( p < 0.01), and coinheritance with - - SEA deletion aggravated the α-thal phenotype , associated with severe Hb H disease . Moreover, a significant difference in the clinical severity was found in the Hb H disease patients with the same genotype.Conclusions: This finding is of great significance for clinicians to provide accurate genetic counseling , particularly prenatal diagnosis and establish a rigorous diagnostic procedure .

Statin-induced adverse effects – facts and genes

2013 ◽  
Vol 154 (3) ◽  
pp. 83-92
Author(s):  
Mariann Harangi ◽  
Noémi Zsíros ◽  
Lilla Juhász ◽  
György Paragh
Keyword(s):  
Risk Factors ◽  
Single Nucleotide Polymorphisms ◽  
Adverse Effects ◽  
Adverse Events ◽  
Statin Therapy ◽  
Significant Proportion ◽  
Gene Mutations ◽  
Nucleotide Polymorphisms ◽  
Serious Adverse Events ◽  
Single Nucleotide

Statin therapy is considered to be safe and rarely associated with serious adverse events. However, a significant proportion of patients on statin therapy show some degree of intolerance which can lead to decreased adherence to statin therapy. The authors summarize the symptoms, signs and frequencies of the most common statin-induced adverse effects and their most important risk factors including some single nucleotide polymorphisms and gene mutations. Also, they review the available approaches to detect and manage the statin-intolerant patients. Orv. Hetil., 2013, 154, 83–92.

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