BETA-GLOBIN GENE MUTATIONS IN TURKISH CHILDREN WITH BETA-THALASSEMIA: RESULTS FROM A SINGLE CENTER STUDY (original) (raw)
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Beta-globin gene mutations in children with beta-thalassemia major from Sanliurfa province, Turkey
Turkish Journal of Hematology, 2011
Objective: The prevalence of β-thalassemia in Şanlıurfa province, Turkey is reported to be 2.6%-3.7%, whereas nationwide the frequency of β-thalassemia is 2%. This study aimed to identify the most frequent β-thalassemia mutations in Şanlıurfa province. Materials and Methods: In total, 22 mutations were investigated in 115 pediatric patients with β-thalassemia using a commercially available reverse dot blot platform. Results: The study included 60 male and 55 female patients with a mean age of 7.3±4.6 years (range: 1-17 years). In total, 76% of the patients had consanguineous parents. In all, 16 different mutations were observed in the 115 patients. IVS-1-110 (G-A) (29.1%), IVS-1-1 (G-A) (13.9%), codon 39 (C>T) (10.4%), and codon 8 (-AA) (9.1%) accounted for 62.5% of all the β-thalassemia mutations, and 6% of the patients had 2 different thalassemia mutations. According to the present results, IVS-1-110 (G>A) was the most frequent mutation observed in the patients from Şanlıurfa province, as in other geographical regions of Turkey. In addition, the following 34 compound heterozygote mutant alleles were observed; IVS-1-1 (G>A)/IVS 2.848 (n=4), codon 39 (C>T)/codon 8 (-AA) (n=2), codon 6 (-A)/IVS 1.5 (G>C) (n=2), IVS-1-110 (G>A)/IVS-1-1 (G>A) (n=2), IVS-1-110 (G>A)/codon 8 (-AA) (n=1), IVS-1-110 (G>A)/codon 39 (C>T) (n=1), IVS-1-110 (G>A)/IVS-1-6 (T>C) (n=1), IVS-1-110 (G>A)/ IVS-1-5 (G>C) (n=1), IVS-1-110 (G>A]/codon 8/9 (+G) (n=1), IVS-1-1 (G>A)/codon 39 (C>T) (n=1), and codon 8 (-AA)/IVS-1-5 (G>C) (n=1). The following β-globin gene promoter mutations were not observed;-101 (C>T),-87(C>T),-30 (T>A), codon 15 (TTG>TGA), codon 27 (G>T) Knossos, and IVS-1-116 (G>C). In all, 5 of the 115 patients (4.3%) had an unidentified mutation. Conclusion: The present results illustrate the heterogeneity of β-thalassemia mutations in Şanlıurfa Province. The present findings may be of value for genetic counseling, and premarital and prenatal diagnosis in Şanlıurfa province.
Beta-globin gene mutations in children with beta-thalassemia major from Şanlıurfa province, Turkey
Turkish Journal of …
Objective: The prevalence of β-thalassemia in Şanlıurfa province, Turkey is reported to be 2.6%-3.7%, whereas nationwide the frequency of β-thalassemia is 2%. This study aimed to identify the most frequent β-thalassemia mutations in Şanlıurfa province. Materials and Methods: In total, 22 mutations were investigated in 115 pediatric patients with β-thalassemia using a commercially available reverse dot blot platform. Results: The study included 60 male and 55 female patients with a mean age of 7.3±4.6 years (range: 1-17 years). In total, 76% of the patients had consanguineous parents. In all, 16 different mutations were observed in the 115 patients. IVS-1-110 (G-A) (29.1%), IVS-1-1 (G-A) (13.9%), codon 39 (C>T) (10.4%), and codon 8 (-AA) (9.1%) accounted for 62.5% of all the β-thalassemia mutations, and 6% of the patients had 2 different thalassemia mutations. According to the present results, IVS-1-110 (G>A) was the most frequent mutation observed in the patients from Şanlıurfa province, as in other geographical regions of Turkey. In addition, the following 34 compound heterozygote mutant alleles were observed; IVS-1-1 (G>A)/IVS 2.848 (n=4), codon 39 (C>T)/codon 8 (-AA) (n=2), codon 6 (-A)/IVS 1.5 (G>C) (n=2), IVS-1-110 (G>A)/IVS-1-1 (G>A) (n=2), IVS-1-110 (G>A)/codon 8 (-AA) (n=1), IVS-1-110 (G>A)/codon 39 (C>T) (n=1), IVS-1-110 (G>A)/IVS-1-6 (T>C) (n=1), IVS-1-110 (G>A)/ IVS-1-5 (G>C) (n=1), IVS-1-110 (G>A]/codon 8/9 (+G) (n=1), IVS-1-1 (G>A)/codon 39 (C>T) (n=1), and codon 8 (-AA)/IVS-1-5 (G>C) (n=1). The following β-globin gene promoter mutations were not observed;-101 (C>T),-87(C>T),-30 (T>A), codon 15 (TTG>TGA), codon 27 (G>T) Knossos, and IVS-1-116 (G>C). In all, 5 of the 115 patients (4.3%) had an unidentified mutation. Conclusion: The present results illustrate the heterogeneity of β-thalassemia mutations in Şanlıurfa Province. The present findings may be of value for genetic counseling, and premarital and prenatal diagnosis in Şanlıurfa province.
2020
Objective: The prevalence of β-thalassemia in Şanlıurfa province, Turkey is reported to be 2.6%-3.7%, whereas nation-wide the frequency of β-thalassemia is 2%. This study aimed to identify the most frequent β-thalassemia mutations in Şanlıurfa province. Materials and Methods: In total, 22 mutations were investigated in 115 pediatric patients with β-thalassemia using a commercially available reverse dot blot platform. Results: The study included 60 male and 55 female patients with a mean age of 7.3±4.6 years (range: 1-17 years). In total, 76% of the patients had consanguineous parents. In all, 16 different mutations were observed in the 115 patients. IVS-1-110 (G-A) (29.1%), IVS-1-1 (G-A) (13.9%), codon 39 (C>T) (10.4%), and codon 8 (-AA) (9.1%) accounted for 62.5% of all the β-thalassemia mutations, and 6% of the patients had 2 different thalassemia mutations. According to the present results, IVS-1-110 (G>A) was the most frequent mutation observed in the patients from Şanlıur...
2011
Objective: The prevalence of β-thalassemia in Şanliurfa province, Turkey is reported to be 2.6%-3.7%, whereas nation-wide the frequency of β-thalassemia is 2%. This study aimed to identify the most fre- quent β-thalassemia mutations in Şanliurfa province. Materials and Methods: In total, 22 mutations were investigated in 115 pediatric patients with β-thalassemia using a commercially available reverse dot blot platform. Results: The study included 60 male and 55 female patients with a mean age of 7.3±4.6 years (range: 1-17 years). In total, 76% of the patients had consanguineous parents. In all, 16 different mutations were observed in the 115 patients. IVS-1-110 (G-A) (29.1%), IVS-1-1 (G-A) (13.9%), codon 39 (C>T) (10.4%), and codon 8 (-AA) (9.1%) accounted for 62.5% of all the β-thalassemia mutations, and 6% of the patients had 2 different thalassemia mutations. According to the present results, IVS-1-110 (G>A) was the most frequent mutation observed in the patients from Şanli...
Spectrum of Beta Globin Gene Mutations in Egyptian Children with Β- Thalassemia
Mediterranean Journal of Hematology and Infectious Diseases, 2014
Background: The molecular defects resulting in a β-thalassemia phenotype, in the Egyptian population, show a clear heterogenic mutations pattern. PCR-based techniques, including direct DNA sequencing are effective on the molecular detection and characterization of these mutations. The molecular characterization of β-thalassemia is necessary for carrier screening, genetic counseling, and to offer prenatal diagnosis. The aim of the work: was to evaluate the different β-globin gene mutations in two hundred β-thalassemic Egyptian children. Subjects and Methods: This study was carried out on two hundred β-thalassemic Egyptian children covering most Egyptian Governorates including 158 (79%) children with thalassemia major (TM) and 42 (21%) children with thalassemia intermedia(TI). All patients were subjected to meticulous history taking, clinical examination, complete blood count, hemoglobin electrophoresis, serum ferritin and direct fluorescent DNA sequencing of the β-globin gene to detect the frequency of different mutations. Results: The most common mutations among patients were IVS I-110(G>A) 48%, IVS I-6(T>C) 40%, IVS I-1(G>A) 24%, IVS I-5(G>C)10%, IVS II-848 (C>A) 9%, IVS II-745(C>G) 8%, IVS II-1(G>A) 7%, codon"Cd"39(C> T) 4%, -87(C>G) 3% and the rare mutations were: Cd37 (G>A), Cd8 (-AA), Cd29(-G), Cd5 (-CT), Cd6(-A), Cd8/9(+G), Cd 106/107(+G), Cd27(C>T), IVS II-16(G> C), Cd 28 (-C), Cap+1(A>C), -88(C>A), all of these rare mutations were present in 1%. There was a considerable variation in phenotypic severity among patients resulting from the interaction of different β° and β+mutations. Furthermore, no genotype-phenotype association was found both among the cases with thalassemia major and the cases with thalassemia intermedia. Conclusion: Direct DNA sequencing provides insights for the frequency of different mutations in patients with β-thalassemia including rare and/or unknown ones. The most common mutations in Mediterr J Hematol Infect Dis 2014; 6; Open Journal System
β globin mutations in Turkish, Northern Iraqi and Albanian patients with β thalassemia major
Thalassemia Reports
The mutation detection of β thalassemia is absolutely necessary for molecular diagnosis, as well as any genetic epidemiological study. The β globin gene has 3 exons and 2 introns, involved in β-thalassemic pathogenesis. The study aim of the study is to characterize the spectrum of β globin gene mutations in 136 Turkish, Northern Iraqi and Albanian pediatric β thalassemia major patients. After genomic DNA extraction from venous blood and amplification of the target DNA regions with PCR, genotyping was achieved by Sanger based DNA sequencing. The IVSI-110 G>A mutation was the most frequent allele in the Turkish and Albanian patients. In Northern Iraqi patients IVSI-1 G>A was is the most frequent. There are two mutations are firstly reported for Albania [c.*111 A>G 3’ UTR (rs63751128) and c.113 G>A (p.Trp38Ter, p.W38*) (rs35887507)] with this study. These findings may be of value for genetic counseling, premarital diagnosis, prenatal diagnosis and prevention programs.
β-Thalassemia mutations and hemoglobinopathies in Adana, Turkey: results from a single center study
β-Thalassemia mutations and hemoglobinopathies in Adana, Turkey: results from a single center study, 2011
Introduction: β-Thalassemia and hemoglobinopathies are common genetic disorders in Turkey and in this retrospective study our aim was to determine the frequency of β-thalassemia and hemoglobinopathies in Adana, which is one of the biggest cities located in the southern part of Turkey. Material and methods: Data from 3000 individuals admitted to Seyhan Hereditary Blood Disorders Center in Adana were evaluated. The blood samples were collected into EDTA-containing tubes and hematological parameters were analyzed using an automatic cell counter. High performance liquid chromatography technique was used to determine the type of hemoglobin. Molecular screening of the β-globin gene was performed with β-Globin Strip Assay. Results: Of 3000 cases, 609 were diagnosed as β-thalassemia or hemoglobinopathy. We have found that the rates of occurrence of β-thalassemia and hemoglobinopathies are 13.46% and 6.83% respectively in this area. We have identified 18 different β-thalassemia mutations and three separate abnormal hemoglobins: HbS, HbD Los Angeles, and HbE. In molecular analyses, β-thalassemia gene mutations of IVSI.110 (G>A), codon 8 (–AA), IVSI.1 (G>A), IVSI.6 (T>C), –30 (T>A), IVSII.1 (G>A), codon 39 (C>T), codon 44 (–C), IVSI.5 (G>C), codon 5 (–CT), codon 8/9 (+G), IVSII.745 (C>G), codon 22 (7bp del), –101(C>T), codon 36/37 (–T), IVSI.15 (T>G), codon 6 (–A), –88 (G>A) were detected. Conclusions: Considering the high incidence of mutations that we have found, β-thalassemia and hemoglobinopathies still seem to be a public health problem in Adana.
Molecular Basis of Beta Thalassemia Mutations in Egyptian Patients
Research Journal of Applied Biotechnology, 2017
Thalassemia is a wide range hereditary disease with high incidence in Egypt along with the high frequency of consanguineous marriages. Investigation the heterogeneity, molecular basis, and natural history are the most effective methods to deal with the thalassemia to develop effective method for management and prevention including the prenatal diagnosis. The current study aims to detect the most common β-globin gene mutations in Egypt among β-thalassemic patients by using PCR based reverse hybridization method (StripAssay) for the most prevalent 22 β-globin gene mutations in the mediterranean population in an attempt to estimate the incidence of each mutation, and an attempt to improve our control strategy of βthalassemia. This study included a total of 37 confirmed βthalassemia ethnic Egyptian patients (23 males and 14 females) out of them 17 patients were a thalassemia major and 20 were a thalassemia intermediate. Evaluation of β-thalassemia mutations revealed that, the presence of 9 different β-globin mutations. The most frequent mutation were IVS 1-110[34%], IVS 1-6(23.5%), IVS 1-1(19%), Codon 27[6.5%], IVS 2-848[6.5%], IVS 2-745[2.1%] and IVS 2.1 [2.5%], Codon 39[4%]), and IVS 1.5 [1.5%]. IVS 1-110[G>A] is the commonest homozygous mutation found in 6 out of 14 homozygous cases accounting for about 43% of homozygous mutations while, IVS 1-110[G>A]/ IVS 1-6[T>C] is the commonest heterozygous mutation found in 6 out of 23 heterozygous cases accounting for about 26% of heterozygous mutations. In conclusion,β-Globin Strip Assay is useful rapid screening method for β-globin gene mutations which can provide an insight into the detection of individual patients, to take the proper measurement, and thus could be used as a basis for genetic counseling and prenatal diagnosis.
Genotype – Phenotype Correlations of β-Thalassemia Mutations in Azerbaijani population
Turkish Journal of Hematology, 2017
β-Talasemi Azerbaycan'da görülen en sık kalıtsal hastalıktır. Çalışmamızın amacı Azerbaycan popülasyonunda en sık görülen β-talasemi mutasyonlarının genotip-fenotip korelasyonlarının ortaya çıkarılmasıydı. Yerel popülasyonda en sık görülen β-globin gen mutasyonları olan kodon 8 (-AA), IVS-I-6 (T>C) ve IVS-II-1 (G>A) mutasyonlarını taşıyan hastalar hematolojik parametreler açısından değerlendirildi. Daha önceden test edilmiş ve genotipik özellikleri bilinen 55 hasta çalışmaya dahil edildi. Mutasyonların fenotipik manifestasyonlarının gösterilmesi için hematolojik indeksler ve hemoglobin fraksiyonlarına bakıldı. Sonuçlar farklı β-globin gen mutasyonları arasında klinik başvuru açısından farklılıklar olduğunu göstermekteydi: IVS-I-6 (T>C) mutasyonu olan bireylerde hastalık kodon 8 (-AA) ve IVS-II-1 (G>A) mutasyonu olanlara göre daha hafif seyretmekteydi. Erken genotipik tanımlama klinik başvuru özelliklerinin tahmin edilmesine ve hastalara en iyi terapötik yaklaşımların uygulanmasına yardımcı olabilir.