Characterization of beta-thalassemia mutations in patients from the state of Rio Grande do Norte, Brazil

Silveira, Zama Messala Luna da; Barbosa, Maria das Vitórias; Fernandes, Thales Allyrio Araújo de Medeiros; Kimura, Elza; Costa, Fernando Ferreira; Sonati, María de Fátima; Rebecchi, Ivanise Marina Moretti; Medeiros, Tereza Maria Dantas de

doi:10.1590/s1415-47572011005000032

Cited by 15 publications

(9 citation statements)

References 15 publications

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“…The β-thal prevalence in North and Northeast Brazil is still undetermined and the few studies from this region to report molecular aspects showed a higher prevalence of HBB: c.92þ6T>C and HBB: c.92þ1G>A. However, the HBB: c.92þ5G>C [IVS-I-5 (G>C); β nt 147 (G>C)], an Indian-Asian mutation mostly described on the Indian subcontinent, Pakistan, Sri Lanka, Mauritius Island, Oman and other part of the Middle East, has also been found (13)(14)(15).…”

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Prevalence and Molecular Characterization of β-Thalassemia in the State of Bahia, Brazil: First Identification of MutationHBB: c.135delC in Brazil

2013

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β-Thalassemia (β-thal) is a hereditary disease with at least 200 known causative molecular defects, with a limited number of distinct mutations predominating in any given population. The Brazilian population is one of the most heterogeneous in the world. Although occurrences of β-thal in this country have been recognized for a long time and previous studies have shown important regional differences related to the mutational profile, no extensive analysis of mutations of the HBB gene has been carried out in Brazil. We examined 1011 teenagers from Bahia, a state located in the northeast of Brazil. Hematological data were obtained using automated cell counting, hemoglobin (Hb) profiles were studied by high performance liquid chromatography (HPLC), and DNA was analyzed by automated sequencing. None of the four Mediterranean mutations that are most frequently found in South and Southeast Brazil (HBB: c.118C>T; HBB: c.93-21G>A; HBB: c.92+1G>A; HBB: c.92+6T>C), was found to be responsible for thalassemia in the cases that we studied. One heterozygote for a frameshift mutation at codon 44 (-C) was identified. This is the first study to determine the prevalence and profile of β-thal in Bahia State. For the first time in Brazil, we report the occurrence of the HBB: c.135delC mutation in the β-globin gene.

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Prevalence and Molecular Characterization of β-Thalassemia in the State of Bahia, Brazil: First Identification of MutationHBB: c.135delC in Brazil

2013

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“…Different from the other states in our study, the most common mutation in the state of Pernambuco was IVS-I-5 (G>C). This mutation is very common in Asia, especially in Malaysia and Indonesia and in several regions of India [29]. In studies conducted by Khan et al from 2011–2013 in four provinces of Pakistan, the most frequent mutation detected in a total of 63 samples of β-thalassemia was IVS-I-5(G>C) (33.9%)[30].…”

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Use of an automated pyrosequencing technique for confirmation of sickle cell disease

et al. 2019

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BackgroundThe diagnosis of sickle cell disease (SCD) is made by hemoglobin assays such as high-performance liquid chromatography (HPLC), isoelectric focusing and cellulose acetate or citrate agar electrophoresis. These assays are easy to perform and used in large-scale newborn screening in many countries. These tests however may not easily differentiate Sβ0 thalassemia from SS or identify other hemoglobin variants, and in this case, hemoglobin (HBB) gene sequencing may be necessary.ObjectivesTo develop a high throughput DNA based confirmatory assay for SCD and to detect mutations in the HBB geneMethodsWe developed an automated pyrosequencing technique (PyS) based on QIAGEN technology (Hilden, Germany) to detect homozygous or heterozygous hemoglobin S mutations as well as hemoglobin C mutations. The technique was tested on 2,748 samples from patients enrolled in a multi-center SCD cohort in Brazil. Patients were previously tested using HPLC to diagnose SCD as part of routine clinical care. Any subjects with discrepant results between HPLC and PyS or with heterozygous hemoglobin S detected had Sanger sequencing of the HBB gene.ResultsWe identified 168 samples with discrepant results between HPLC and PyS and 100 with concordant PyS = heterozygous S and HPLC, which would suggest SB-thalassemia or other heterozygous S variants. The PyS assay correctly identified 1906 (98.7%) of the 1930 HbSS and 628 (98.7%) of the 636 HbSC samples. Of the 179 remaining samples, PyS correctly indicated S heterozygosis in 165 (92.2%). Of the 165 heterozygous S samples confirmed by Sanger as consistent with Sβ thalassemia genotype, 84 samples were classified as Sβ0 thalassemia and 81 as Sβ+ thalassemia. The most frequent beta thalassemia mutations of Sβ0 and Sβ+ were HBB: c.118C>T (Gln40Stop) and HBB c.92 + 6T> C, respectively.DiscussionThe PyS proved to be satisfactory for large-scale confirmatory testing of hemoglobin mutation. Moreover, with this study we were able to describe the most common β+ and β0 mutations in SCD patients with Sβ-thalassemia in a large multi-institutional SCD cohort in Brazil.

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“…Hematological and biochemical studies by others of other populations with similar or different mutation patterns showed significant changes in these characteristics between different mutations. In a Brazilian population where IVS-I-110, IVS-I-6 and IVS-I-1 are predominant mutations [31,32], Bertuzzo et al [33] showed that IVS-I-1 was the relatively severe mutation and IVS-I-6 was the mildest one, while IVS1-110 was intermediate in severity. In a Pakistani study, Khattak et al [34] reported a frame shift mutation, FR 8-9, to have the lowest hematological RBC parameters.…”

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confidence: 99%

Genotype-phenotype characteristics of β thalassemia children in the Gaza Strip, Palestine

Sirdah¹

2013

J Genet Disor Genet

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Characterization of beta-thalassemia mutations in patients from the state of Rio Grande do Norte, Brazil

Cited by 15 publications

References 15 publications

Prevalence and Molecular Characterization of β-Thalassemia in the State of Bahia, Brazil: First Identification of MutationHBB: c.135delC in Brazil

Prevalence and Molecular Characterization of β-Thalassemia in the State of Bahia, Brazil: First Identification of MutationHBB: c.135delC in Brazil

Use of an automated pyrosequencing technique for confirmation of sickle cell disease

Genotype-phenotype characteristics of β thalassemia children in the Gaza Strip, Palestine

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