Mutations and haplotype diversity in 70 Portuguese G6PD-deficient individuals: an overview on the origin and evolution of mutated alleles

Manco, Licínio; Gonçalves, Paula; Antunes, Patrı́cia; Maduro, Filomena; Abade, Augusto; Ribeiro, Maria Letı́cia

doi:10.3324/haematol.11670

Cited by 12 publications

(7 citation statements)

References 6 publications

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“…In the present study the analysis of the phenotypically deficient subjects has led to the detection of other 3 uncommon mutations, some of which have never been described in the area. Açores variant (Ile199Val) has been described only in Portugal so far [24] . Seattle variant (Asp282His, also called Lodi/Modena, FerraraII, Seattle-like) has been found repeatedly and characterized in Italy [25] and found in the Canary Islands [26] and in Greece [27] .…”

Section: Discussionmentioning

confidence: 99%

Characterization of G6PD Genotypes and Phenotypes on the Northwestern Thailand-Myanmar Border

et al. 2014

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Mutations in the glucose-6-phosphate dehydrogenase (G6PD) gene result in red blood cells with increased susceptibility to oxidative damage. Significant haemolysis can be caused by primaquine and other 8-aminoquinoline antimalarials used for the radical treatment of Plasmodium vivax malaria. The distribution and phenotypes of mutations causing G6PD deficiency in the male population of migrants and refugees in a malaria endemic region on the Thailand-Myanmar border were characterized. Blood samples for G6PD fluorescent spot test (FST), G6PD genotyping, and malaria testing were taken from 504 unrelated males of Karen and Burman ethnicities presenting to the outpatient clinics. The overall frequency of G6PD deficiency by the FST was 13.7%. Among the deficient subjects, almost 90% had the Mahidol variant (487G>A) genotype. The remaining subjects had Chinese-4 (392G>T), Viangchan (871G>A), Açores (595A>G), Seattle (844G>C) and Mediterranean (563C>T) variants. Quantification of G6PD activity was performed using a modification of the standard spectrophotometric assay on a subset of 24 samples with Mahidol, Viangchan, Seattle and Chinese-4 mutations; all samples showed a residual enzymatic activity below 10% of normal and were diagnosed correctly by the FST. Further studies are needed to characterise the haemolytic risk of using 8-aminoquinolines in patients with these genotypes.

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Section: Discussionmentioning

confidence: 99%

Characterization of G6PD Genotypes and Phenotypes on the Northwestern Thailand-Myanmar Border

et al. 2014

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“…The hexokinase and glucose 6-phosphate dehydrogenase (G6PD), involved in glycometabolism, play essential roles in promoting erythrocyte hemolysis (Verdugo, Calvanese, Rodríguez, & Cárcamo, 2014). The study has shown that individuals with G6PD defect develop hemolysis challenged with oxidative stress (Manco et al, 2005). Exudative diathesis (ED) is the main clinical symptom in broilers caused by single Se-deficient diet, and the blue (green) purple color presented in the abdomen of diseased broilers is closely related to hemoglobin (Hb) metabolism.…”

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confidence: 99%

Oxidative stress, inflammation, and glycometabolism disorder‐induced erythrocyte hemolysis in selenium‐deficient exudative diathesis broilers

Zheng

Zhao

Xing

et al. 2019

Journal Cellular Physiology

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Selenium (Se) deficiency causes injury of diversified tissues and cells, including livers, hearts, skeletal muscles, and erythrocytes. The aim of the present study is to explore the molecular mechanism of erythrocyte hemolysis due to Se deficiency in broilers. One hundred and eighty broilers (male/female, 1 day old) were randomly divided into two groups and fed with either a normal Se content diet (C group, 0.2 mg Se/kg) or a Se‐deficient diet (ED group, 0.008 mg Se/kg) for 45 days. During the trial period of 15–30 days, biological properties such as osmotic fragility, fluidity, phospholipid components of cell membrane, adenosine triphosphatase activities, and antioxidant function of erythrocytes in broilers were examined. Moreover, the messenger RNA (mRNA) expressions of genes associated with inflammation, glycometabolism, and avian uncoupling protein (avUCP) were detected. We found that compared with the C group, hemolysis rate, degree of polarization, and microviscosity of erythrocytes were increased in broilers of the ED group. The composition of erythrocyte membrane lipids was changed. Meanwhile, the antioxidant function of erythrocytes was weakened and mRNA levels of inflammatory genes were stimulated by Se deficiency (p < 0.05). In addition, mRNA expressions of rate‐limiting enzymes in glycometabolism were effected and avUCP mRNA level was downregulated (p < 0.05) in the ED group. It has been concluded from the results that oxidative stress, inflammatory response, and glycometabolism disorder lead to erythrocyte hemolysis by changing the structure and function of erythrocyte membrane in ED broilers suffered from Se deficiency.

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“…Of the 18 rare variants identified, six were, to the best of the authors' knowledge, only found in the Portuguese population, having already been the subject of previous publications [14][15][16] : they are the G6PD variants known as Mira d'Aire (c.1048G>A), Anadia (c.1193A>G), Tondela (c.l1076-c.1094del), Covão do Lobo (c.1205C>A), Figueira da Foz (c. 1366G>C) and Flores (c.1387C>A) (Table 1). The variant G6PD Azores (c.595A>G) was also found in Papua New Guinea and named as G6PD Dagua.…”

Section: Discussionmentioning

confidence: 83%

“…25 This study describes five rare G6PD variants previously identified in other populations around the world but reported herein for the first time in the Portuguese population: Vanua Lava (c.383T>C), Taipei (c.493A>G), Shinshu (c.527A>G), Mexico City (c.680G>A) and Kaiping (c.1388G>A). 11 The G6PD variants Chatham (c.1003G>A), Canton (c.1376G>T) and Kamiube (c.1387C>T) were previously described in Portuguese individuals 15 and the variants Seattle (c.844G>C) and Mediterranean (c.563C>T), also found in this study, had already been previously identified in Portugal by Rodrigues et al 14 The variant G6PD Coimbra, identified in three chromosomes, was previously found in a Portuguese patient, 26 and it is common in several Asian populations. Two mutations previously described in the Portuguese population, G6PD Aveiro (c.806G>A) 27 and G6PD Gaohe (c.95A> G), 14 were not found in this study.…”

Section: Discussionmentioning

confidence: 99%

“…This retrospective study assessed the mutational profile of 138 Portuguese individuals with G6PD deficiency (101 males and 37 females; aged between 2 and 74 years), diagnosed between 1994 and 2020, based on recent data and results obtained in past periods, some of which have been published. 15,16 All individuals, unrelated and with no known sub-Saharan ancestry, were mostly from central Portugal (about 65%), but also from the southern (about 15%) and northern (about 8%) regions, and the Azores archipelago (about 2%). In about 10% of the cases, it was not possible to identify the place of birth.…”

Section: Materials and Methods Populationmentioning

confidence: 99%

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Heterogeneidade Molecular da Deficiência em Glicose-6-Fosfato Desidrogenase (G6PD) na População Portuguesa

et al. 2022

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Introduction: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme defect in the world, affecting more than 500 million people. In Portugal, the average frequency of G6PD deficiency in males was estimated at about 0.5% and since the year 2000 several G6PD-deficient alleles have been identified. The main goal of this study was to improve the knowledge on the molecular heterogeneity of G6PD deficiency in the Portuguese population.Material and Methods: A retrospective analysis of the mutational profile of 138 unrelated Portuguese individuals (101 males; 37 females), with no known sub-Saharan ancestry, who had been diagnosed with G6PD deficiency between 1994 and 2020 at the Molecular Hematology Unit of Centro Hospitalar e Universitário de Coimbra. The molecular study was done by direct Sanger sequencing or PCR-RFLP analysis.Results: Twenty-one different pathogenic mutations were found. Among them, 20 were missense, causing the amino acid change, and one was an in-frame deletion in exon 10. The three most frequent mutations belong to the G6PD c.376A>G African background haplotype, namely the G6PD variants: A- (c.202G>A; p.68Val>Met) (58.6%), Betica (c.968T>C; p.323Leu>Pro) (12.1%) and Santamaria (c.542A>T; p.181Asp>Val) (4.3%).Conclusion: There is a wide molecular heterogeneity of G6PD deficiency in the Portuguese population.

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Mutations and haplotype diversity in 70 Portuguese G6PD-deficient individuals: an overview on the origin and evolution of mutated alleles

Cited by 12 publications

References 6 publications

Characterization of G6PD Genotypes and Phenotypes on the Northwestern Thailand-Myanmar Border

Characterization of G6PD Genotypes and Phenotypes on the Northwestern Thailand-Myanmar Border

Oxidative stress, inflammation, and glycometabolism disorder‐induced erythrocyte hemolysis in selenium‐deficient exudative diathesis broilers

Heterogeneidade Molecular da Deficiência em Glicose-6-Fosfato Desidrogenase (G6PD) na População Portuguesa

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