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.

scholarly journals Complex Interaction of Hb Q-Thailand with α and β Thalassemia in a Hakka Family

2020 ◽  
Author(s):  
Lin Zheng ◽  
Hailong Huang ◽  
Xiaoqing Wu ◽  
Qingmei Shen ◽  
Meihuan Chen ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Hematological Parameters ◽  
Globin Gene ◽  
Family Members ◽  
Migration Time ◽  
Fujian Province ◽  
Her Family ◽  
Microcytic Hypochromic Anaemia ◽  
Haemoglobin Disorders ◽  
Abnormal Band

Abstract Background HbQ-Thailand is an α-globin chain variant that results from a point mutation at codon 74 of the α1-globin gene on chromosome 16p. It commonly appears with a leftward single α-globin gene deletion (-α 4.2 ). There have been few reports regarding the interaction between HbQ-Thailand and other globin gene disorders. Here we found and diagnosed it in the Hakka population of the Fujian Province, China. The study provides an important reference for the clinic diagnose and genetic counseling of thalassemia and hemoglobin diseases. Methods Fresh peripheral blood samples were collected from the proband and her family members testing hematological parameters, hemoglobin components, thalassemia gene, and hemoglobin variants. Results The proband (II1) and her sister (II5) manifested in the obvious microcytic hypochromic anaemia. The CE electropherogram of II1 showed an abnormal band in the migration time at 185 s, which was confirmed as HbQ-Thailand. Another exception band appeared at 250 s of migration time and was proved to be HbE by sequence analysis method. The CE electropherogram of I1 and II3 showed an anomalous band HbE. The mother of the proband (I2) and the III4 and III5 of the family members showed a HbQ-Thailand. The gene results showed that the father (I1) also carried α- and β-thalassemia genes. His genotype was -- SEA and β codons26 ; -- SEA was inherited to II1, II 3, II5, III 1, and III2, and β codons26 was inherited to II1 and II3. The mother (I2) carries the -α 4.2 gene, which was inherited to II1, II5, III4, and III5. Conclusion It was complex to diagnose when the thalassemia combined with several abnormal haemoglobin disorders, and we may use various methods to mutual confirmation. Here we found and diagnosed a rare hemoglobin disease in the Hakka population of the Fujian Province. The study provides an important reference for the clinic diagnose and genetic counseling.

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 Prevalence and clinical phenotype of the triplicated α-globin genes and its ethnic and geographical distribution in Guizhou of China

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xi Luo ◽  
Xiang-mei Zhang ◽  
Liu-song Wu ◽  
Jindong Chen ◽  
Yan Chen
Keyword(s):  
Genetic Counseling ◽  
Peripheral Blood ◽  
Clinical Phenotype ◽  
Globin Gene ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Guizhou Province ◽  
Globin Genes ◽  
Phenotype Correlation ◽  
Chi Square

Abstract Background α-thalassemia is relatively endemic in Guizhou province of southwestern China. To predict the clinical manifestations of α-globin gene aberration for genetic counseling, we examined the prevalence of the α-globin triplication and the genotype–phenotype correlation in this subpopulation Methods A cohort of 7644 subjects was selected from nine ethnicities covering four regions in Guizhou province of China. Peripheral blood was collected from each participant for routine blood testing and hemoglobin electrophoresis. PCR-DNA sequencing and Gap-PCR were used to identify the thalassemia gene mutations. Chi-square tests and one-way analysis of variance (ANOVA) were used to statistically analyze the data. Results We found that the frequency of α-globin triplication in Guizhou province was 0.772% (59/7644). Genotypically, the αααanti4.2/αα accounted for 0.523% (40/7644), the αααanti3.7/αα for 0.235% (18/7644), and the αααanti3.7/–SEA for 0.013% (1/7644). The αααanti4.2/αα is more prevalent than the αααanti3.7/αα in Guizhou. In addition, the frequency of the HKαα/αα (that by GAP-PCR is like αααanti4.2/-α3.7) was 0.235% (18/7644). Ethnically, the Tujia group presented the highest prevalence (2.47%) of α-globin triplication. Geographically, the highest frequency of the α-globin triplication was identified in Qiannan region (2.23%). Of the triplicated α-globin cases, 5 coinherited with heterozygote β-thalassemia and presented various clinical manifestations of anemia. Conclusions These data will be used to update the Chinese triplicated α-globin thalassemia database and provide insights into the pathogenesis of thalassemia. These findings will be helpful for the diagnosis of thalassemia and future genetic counseling in those regions.

Hemoglobin variants, hematological parameters andβ-globin gene cluster haplotypes in an isolated Amerindian group from the Orinoco River Delta

2008 ◽  
Vol 35 (2) ◽  
pp. 250-255 ◽  
Author(s):  
Anabel Arends ◽  
Marycarmen Chacín ◽  
Martha Bravo-Urquiola ◽  
Tibisay Arends De O ◽  
Maritza Álvarez ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Hematological Parameters ◽  
Globin Gene ◽  
River Delta ◽  
Orinoco River ◽  
Globin Gene Cluster ◽  
Hemoglobin Variants

Spectrum of Genetic Mutation in Beta Globin Gene in Various Type of Thalassaemia in Bangladesh

2021 ◽  
Vol 5 (02) ◽  
pp. 57-60
Author(s):  
Nishat Mahzabin ◽  
Md. Akhlak-Ul- Islam ◽  
Kazi Mohammad Kamrul Islam ◽  
Khaza Amirul Islam ◽  
Md. Arif-Ur- Rahman ◽  
...  
Keyword(s):  
Globin Gene ◽  
Phenotypic Expression ◽  
Gene Mutations ◽  
Cross Sectional Study ◽  
Genetic Mutation ◽  
Compound Heterozygous ◽  
Cross Sectional ◽  
Beta Thalassaemia ◽  
Hb E ◽  
Beta Gene

Background: Hb-E/Beta thalassaemia is a congenital haemoglobin disorder which is a compound heterozygous state consists of qualitative disorder like Hb E variant & quantitative Hb disorder caused by genetic mutation of Beta chain. Objective: The aim of the study was to identify the beta gene mutation in Hb E/Beta thalassaemia. Method: A total of 32 diagnosed Hb E/Beta thalassaemia patients were included in this cross-sectional study from May 2019 to July 2020. Genetic analysis was done by sanger sequencing. Results: In this observational study, we found 13 different types of Beta gene mutations. Heterozygous for IVS 1-5(G>C) mutation was most frequent (53.1%). Conclusion: Genetic mutation is the confirmatory diagnosis for thalassaemia as well as one of the main factors for clinical expression. Mutation pattern also varies according to the geographical distribution. So, this study shows the frequently found mutation in Bangladesh and should carry out routinely to point out phenotypic expression.

The Correlation of α-Globin Gene Mutations and theXmnI Polymorphism with Clinical Severity of Hb E/β-Thalassemia

Hemoglobin ◽  
2014 ◽  
Vol 38 (5) ◽  
pp. 335-338 ◽  
Author(s):  
Pimlak Charoenkwan ◽  
Pimjan Teerachaimahit ◽  
Torpong Sanguansermsri
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
Clinical Severity ◽  
Hb E

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.

The Carrier Frequency of α-Globin Gene Triplication in an Iranian Population with Normal or Borderline Hematological Parameters

Hemoglobin ◽  
2011 ◽  
Vol 35 (4) ◽  
pp. 323-330 ◽  
Author(s):  
Seyedeh Fatemeh Moosavi ◽  
Azam Amirian ◽  
Behnaz Zarbakhsh ◽  
Alireza Kordafshari ◽  
Hasan Mirzahoseini ◽  
...  
Keyword(s):  
Carrier Frequency ◽  
Hematological Parameters ◽  
Globin Gene ◽  
Iranian Population
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