Mutation Analysis of the HBB Gene in Selected Bangladeshi β-Thalassemic Individuals: Presence of Rare Mutations (original) (raw)
Related papers
Spectrum of Genetic Mutation in Beta Globin Gene in Various Type of Thalassaemia in Bangladesh
Haematology Journal of Bangladesh, 2021
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 phenoty...
Mutational Studies of Gene HBB in β-Thalassemia Patients from Balochistan, Pakistan
Current Trends in OMICS, 2021
Thalassemia is a hereditary blood disorder. It occurs due to two mutations in the HBB gene located on chromosome 11. This gene has 1606 base pairs and contains three exons. Moreover, HBB gene codes for β globin protein have been identified to posses 868 mutations, which comprise point mutation, insertion, deletion, and gene arrangement. In β thalassemia major, both alleles are mutated and no β chain is synthesized. In this study, three human families with thalassemia were selectedfrom different areas of Balochistan. For DNA extraction and estimation, 5 ml blood samples were extracted intravenously from the affected individuals, their normal siblings, and parents in 15ml falcon tubes containing 200μl EDTA. Primer sequences were designed on primer 3 for the mutational analysis of the HBB gene. Since the gene has a total of three exons and two introns, three primers, namely HBBX1, HBBX2 and HBBX3, were designed. These primers were used to amplify the HBB gene responsible for β thalasse...
2021
Background: Hemoglobin E/β-thalassemia is a common inherited hemoglobin disorder among South Asian countries. The phenotypically diverse presentation of the disease is often attributed to coinheritance of β-globin (HBB) gene mutations. The current study described the phenotype and genetic basis of Hb E/β-thalassemia patients and assessed its relation with clinical severity.Methods: A total of 32 patients were included in this cross-sectional study. Cases were confirmed by using capillary hemoglobin electrophoresis or high-performance liquid chromatography. Those with positive findings were further analyzed with clinical information and ancestral data either from the interview or medical records. Data collection was confined to May 2019 and July 2020. Gene sequencing was performed using Sanger’s sequencing method for mutational analysis, and Mahidol scoring was used to grade clinical severity.Result: A total of 13 heterozygous mutations were identified in the HBB gene. Of all, IVS-1-...
Hemoglobin, 2019
In Bangladesh, the practice of b-thalassemia (b-thal) carrier screening and prenatal diagnosis (PND) by b-globin gene sequencing has been initiated to prevent the birth of affected children. The study aimed to describe a novel de novo mutation of the b-globin gene and its clinical implication. Out of 100 Bangladeshi b-thal carrier families, one patient with hematological and clinical features associated with b-thal and her parents were included. Molecular characterizations of b-globin gene mutations were performed by direct sequencing. A novel nucleotide deletion mutation at codon 8 in the first exon of the b-globin gene (HBB: c.27delG) was found in a 1-year-old child of the studied family in a heterozygous state along with common Hb E (HBB: c.79G>A). The mutation caused a frameshift to a new stop codon at codon 18 resulting in a b 0-thal phenotype. The proband exhibited a b-thal intermedia (b-TI)like genotype, however, showed b-thal major (b-TM)-like complications and was transfusion-dependent. Her mother had a profile consistent with the Hb E trait, while the father had normal hematological indices. Mutation analyses revealed the mother to be heterozygous for Hb E, while the father had a normal genotype. The novel mutation was assumed to be inherited de novo by the paternity test. The study documented a novel pathogenic mutation in the b-globin gene in a Bangladeshi family by b-globin gene sequencing.
Orphanet Journal of Rare Diseases
Background: ß-thalassemia is one of the most common inherited blood disorders in the world and a major deterrent to the public health of Bangladesh. The management of thalassemia patients requires lifelong frequent blood transfusion and the available treatment options are unsatisfactory. A national policy on thalassemia prevention is mandatory in Bangladesh. However, precise and up-to-date information on the frequency of ß-thalassemia carriers are missing due to lack of accurate diagnostic approaches, limited access to information and absence of national screening program. This study aims to determine the nationwide carrier frequency of hemoglobin E (HbE) and βthalassemia and mutation spectrum among the carriers using molecular, hematological and biochemical methods. Methods: The study enrolled a total of 1877 individuals (60.1% male and 39.9% female) aged between 18 and 35 years. Total sample size and its division-wise breakdown were calculated in proportion to national and division-wise population. Venous blood was collected and subjected to CBC analysis and Hb-electrophoresis for each participant. Serum ferritin was measured to detect coexistence of iron deficiency anemia with thalassemia carrier. DNA-based High Resolution Melting (HRM) curve analysis was performed for confirmation of carrier status by mutation detection. Results: Of 11.89% (95% CI, 10.43-13.35) carriers of β-globin gene mutations, 8.68% (95% CI, 7.41-9.95) had HbE trait (ETT) and 2.24% (95% CI, 1.57-2.91) had beta-thalassemia trait (BTT). Among eight divisions, Rangpur had the highest carrier frequency of 27.1% (ETT-25%, BTT-2.1%), whereas Khulna had the lowest frequency of 4.2% (ETT-4.2% only). Moreover, αthalassemia, HbD trait, HbE disease, hereditary persistence of HbF were detected in 0.11, 0.16, 0.43 and 0.16% participants, respectively. HRM could identify two individuals with reported pathogenic mutations in both alleles who were erroneously interpreted as carriers by hematological indices. Finally, a total of nine different mutations including a novel mutation (c.151A > G) were detected in the β-globin gene. Conclusions: Since carrier frequency for both HbE and β-thalassemia is alarmingly high in Bangladesh, a nationwide awareness and prevention program should be made mandatory to halt the current deteriorating situations. Mutationbased confirmation is highly recommended for the inconclusive cases with conventional carrier screening methods to avoid any faulty detection of thalassemia carriers.
β-Thalassemia Caused by De novo Mutation in the β globin Gene Identified in Two Bangladeshi Families
Journal of Blood Disorders & Transfusion
De novo mutations represent a unique example of how rare mode of inheritance of genetic variations can influence the onset of genetic diseases. Most of the mutations causing β-thalassemia in Bangladeshi population were found to be inherited germ line. The study aimed to present two cases of De novo mutations of the β-globin gene causing β thalassemia. Out of one hundred Bangladeshi β-thalassemia carrier families who were advised for both pre and postnatal molecular characterization of the β-globin gene to detect the mutation, two cases of De novo mutations were identified in two Bangladeshi families, which is the first of this type of mutation inheritance in Bangladesh. Mutations were determined by sequencing of the entire β-globin gene by Sanger method. In one family as case A, the foetus proband in the amniotic fluid was found homozygous for the mutation in the codon 26 (G>A) (G>A) [HBB: c.79G>A] and was diagnosed as the β-thalassemia major. The paternal allele was normal and only the mother carried one mutant allele. In another family as case B, the proband in the blood of the affected child was found homozygous for the mutation IVS-I-5 (G>C) [HBB: c.92+G>C]. The father did not carry any mutation while the mother was heterozygous for the mutation. In both cases, the possibility of non-paternity was excluded by using STR-based parentages testing, indicating that the acquired mutation in the probands was the result of a De novo event. The study demonstrates the significance of the prenatal diagnosis of β-thalassemia by DNA sequencing to detect novel, rare or De novo mutation that cannot be identified during screening by haemoglobin electrophoresis.
Diagnostics
Background: β-thalassaemia is a disorder caused by mutations in the β-globin gene, leading to defective production of haemoglobins (Hb) and red blood cells (RBCs). It is characterised by anaemia, ineffective erythropoiesis, and iron overload. Patients with severe β-thalassaemia require lifelong blood transfusions. Haemoglobin E beta-thalassaemia (HbE/β-thalassaemia) is a severe form of β-thalassaemia in Asian countries. More than 200 alleles have been recognised in the β-globin region. Different geographical regions show different frequencies of allelic characteristics. In this study, the spectrum of β-thalassaemia (β-thal) alleles and their correlation with iron overload, in HbE/β-thalassaemia patients, β-thalassaemia trait, and HbE trait were studied. Methods: Blood samples (n = 260) were collected from 65 β-thalassaemia patients, 65 parents (fathers and/or mothers) and 130 healthy control individuals. Haematological analyses, iron profiles, and serum hepcidin levels were examined...
The Frequency of HBB Mutations Among β-Thalassemia Patients in Hamadan Province, Iran
Hemoglobin, 2017
b-Thalassemia (b-thal) caused by mutations on the HBB gene is the most common single-gene disorder in the world. In this study, the HBB gene mutation was investigated in Hamadan province, Iran. Fortyone patients referred to a referral hospital were admitted to the study. DNA samples were extracted from peripheral blood. The HBB gene was sequenced in all recruited patients. Eleven mutations and eight polymorphisms were found in the studied patients. IVS-II-1 (G>A) (HBB: c.315þ1 G>A) was the most common mutation, accounting for 25.61% of mutant alleles. Other mutations included codon 8 (-AA) (HBB: c.25À26delAA); IVS-I-110 (G>A) (HBB: c.93À21 G>A); codons 8/9 (þG) (HBB: c.27À28insG); IVS-I-1 (G>A) (HBB: c.92 G>A); codon 44 (-C) (HBB: c.135delC); codons 25/26 (þT) (HBB: c.78À79insT); IVS-I-130 (G>C) (HBB: c.93À1 G>C);-28 (A>C) (HBB: c.À78 A>C); codons 36/37 (-T) (HBB: c.112delT) and IVS-I-6 (T>C) (HBB: c.92þ6 T>C). According to our findings, the IVS-II-1 mutation has the highest prevalence in Hamadan Province. It was found that the total frequency of the IVS-II-1, codons 25/26 (þT), codons 8/9 (þG), IVS-I-110 and IVS-I-1 mutations was 82.92%. Therefore, given these findings, it is recommended that these five mutations are screened for as a first step in laboratories without sequencing instruments, and that the rest of the gene is subsequently examined.
Interaction of Thalassemia and Hb Variants in Southeast Asia: Genotype-Phenotype Relationship
IntechOpen eBooks, 2023
Thalassemia and hemoglobinopathies are characterized by globin gene mutations affecting the production of quantitative and structural defects of the globin chain. α-Thalassemia, β-thalassemia, hemoglobin E (Hb E), and hemoglobin Constant Spring (Hb CS) are very common in Southeast Asian countries. Complex interactions of thalassemia and Hb variants are also common and affect the thalassemia diagnosis with several techniques including Hb typing and DNA analysis. A family study (family pedigree) is required in the proband with a complex interaction of several globin gene defects with rare types. Homozygous β-thalassemia, Hb E/β-thalassemia, and Hb Bart's hydrops fetalis are severe thalassemia and these diseases have been concerned and included in the prevention and control program in several countries. Understanding the genotype-phenotype could help with the proper laboratory tests, genetic counseling, and effective treatment for the patients.
International Journal of Population Studies
Thalassemia is a dreadful heritable hemolytic disease, characterized by a genetic mutation in the hemoglobin subunit beta (HBB) gene. Mutation in HBB gene completely halts the production of the beta-globin protein, which leads to the defective production of functional hemoglobin. The prevalence of this disease is reported only in some specific geographical regions of India. Hence, the aim of this study was to screen the population of Garhwal for beta-thalassemia (β-thalassemia) and thus find out the prevalence in the inhabitants through molecular characterization. For this study, 4,081 individuals were considered, out of which only the ones with elevated HbA2 levels (64) were subjected to molecular characterization. Mutational studies were carried out for the five most common mutations prevalent in the Indian subcontinent, that is, IVS 1-5 G-C, IVS 1-1 G-T, Codon 41/42 (-TCTT), Codon 8/9, and 619 bp deletion. The present study reports a frequency of 0.5% for β-thalassemia mutations ...