G6PD deficiency assessment in Freetown, Sierra Leone, reveals further insight into the molecular heterogeneity of G6PD A-

Jalloh, Amadu; Gamanga, Idrissa; Baion, David; Sahr, Foday; Gbakima, Aiah A; Willoughby, V. R.; Matsuoka, Hiroyuki

doi:10.1007/s10038-008-0294-y

Cited by 15 publications

(16 citation statements)

References 12 publications

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“…Besides the mutants described by Minucchi’s review [34], we include the following new variants: Class II G6PD Bahia (Phe66Thr, exon 4) [43], San Luis Potosi (Asn126Tyr; exon 5) [37], Coimbra (Arg198His, exon 6) [45], a class III variant with double mutation; G6PD Sierra Leone (Arg104His, Asn126Asp, exon 5) [46], a class IV G6PD San Paulo mutant (Ile220Met, exon 7) [47]. Finally, we found four mutants that did not classified according to their residual enzyme activity: G6PD Shanghai (Ala231Pro, exon 7) [48], G6PD Karachi (Asp325Asn, exon 9) [49], G6PD Vietnam 1 (Glu3Lys, exon 2) [50], and G6PD Vietnam 2 (Phe66Cys, exon 4) [50] which are shown in the Figure 4.…”

Section: Molecular Characterization Of G6pd Variantsmentioning

confidence: 99%

“…Jalloh et al [46] reported the Class III G6PD Sierra Leona variant, which has double mutation in exon 5 (311G > A and 376A > G) leading to the change of amino acid 104 Arg → His and 126 Asn → Asp, respectively. This mutation drastically reduces G6PD activity [46].…”

Section: Molecular Characterization Of G6pd Variantsmentioning

confidence: 99%

“…This mutation drastically reduces G6PD activity [46]. In addition, Oliveira et al [47] reported a novel Class IV G6PD Sao Paulo variant 660C > G that was detected in exon 7, this mutation led to replacement of isoleucine by methionine (I220M) whose location is near the dimer interface (Figure 4).…”

Section: Molecular Characterization Of G6pd Variantsmentioning

confidence: 99%

“…Furthermore, unrelated events to these agents have been reported such diabetes, myocardial infarction, or even vigorous exercise which can trigger hemolysis [70,74,75]. Mutants with these clinical manifestations are the G6PD Tunis and Sierra Leone variants that were found in a 54 year-old female and 15-year-old boy presenting hemolytic anemia and a very low residual enzyme, respectively [46,56]. …”

Section: Clinical G6pd Deficiencymentioning

confidence: 99%

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Glucose-6-Phosphate Dehydrogenase: Update and Analysis of New Mutations around the World

Gómez-Manzo

Marcial-Quino

Vanoye-Carlo

et al. 2016

IJMS

177

147

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Glucose-6-phosphate dehydrogenase (G6PD) is a key regulatory enzyme in the pentose phosphate pathway which produces nicotinamide adenine dinucleotide phosphate (NADPH) to maintain an adequate reducing environment in the cells and is especially important in red blood cells (RBC). Given its central role in the regulation of redox state, it is understandable that mutations in the gene encoding G6PD can cause deficiency of the protein activity leading to clinical manifestations such as neonatal jaundice and acute hemolytic anemia. Recently, an extensive review has been published about variants in the g6pd gene; recognizing 186 mutations. In this work, we review the state of the art in G6PD deficiency, describing 217 mutations in the g6pd gene; we also compile information about 31 new mutations, 16 that were not recognized and 15 more that have recently been reported. In order to get a better picture of the effects of new described mutations in g6pd gene, we locate the point mutations in the solved three-dimensional structure of the human G6PD protein. We found that class I mutations have the most deleterious effects on the structure and stability of the protein.

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Section: Molecular Characterization Of G6pd Variantsmentioning

confidence: 99%

Section: Molecular Characterization Of G6pd Variantsmentioning

confidence: 99%

Section: Molecular Characterization Of G6pd Variantsmentioning

confidence: 99%

Section: Clinical G6pd Deficiencymentioning

confidence: 99%

See 2 more Smart Citations

Glucose-6-Phosphate Dehydrogenase: Update and Analysis of New Mutations around the World

Gómez-Manzo

Marcial-Quino

Vanoye-Carlo

et al. 2016

IJMS

177

147

View full text Add to dashboard Cite

show abstract

“…13 Although the G6PDd A− variant makes up the vast majority of G6PDd cases in most West African populations, there are other G6PDd mutations that do reach polymorphic levels in some populations. 14,15 Further studies should investigate the distribution of the A− variant in other parts of Haiti and include full G6PD gene sequence data with G6PDd phenotype data, to obtain a more complete picture of the genetic background of G6PDd in Haiti, as the severity of hemolytic anemia after primaquine exposure varies based on G6PDd genotypes. Additionally, more studies should follow response to primaquine treatment in G6PD A− individuals in Haiti to confirm that hemolytic anemia is not a high risk at the new recommended lower dose.…”

mentioning

confidence: 99%

Glucose-6-Phosphate Dehydrogenase Deficiency A− Variant in Febrile Patients in Haiti

Carter

Maloy

Fricken

et al. 2014

The American Society of Tropical Medicine and Hygiene

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Abstract. Haiti is one of two remaining malaria-endemic countries in the Caribbean. To decrease malaria transmission in Haiti, primaquine was recently added to the malaria treatment public health policy. One limitation of primaquine is that, at certain doses, primaquine can cause hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd). In this study, we genotyped two mutations (A376G and G202A), which confer the most common G6PDd variant in West African populations, G6PDd A−. We estimated the frequency of G6PDd A− in a sample of febrile patients enrolled in an on-going malaria study who represent a potential target population for a primaquine mass drug administration. We found that 33 of 168 individuals carried the G6PDd A− allele (includes A− hemizygous males, A− homozygous or heterozygous females) and could experience toxicity if treated with primaquine. These data inform discussions on safe and effective primaquine dosing and future malaria elimination strategies for Haiti.Glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) is a genetic red blood cell disorder caused by mutations in the G6PD gene on the X chromosome. The reduced G6PD enzyme concentration increases oxidative damage in red blood cells resulting in hemolysis. One of the more common G6PDd variants, G6PDd A−, has only 12% enzyme activity and reaches frequencies as high as 20% in West African populations.

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Multi‐gene panel testing improves diagnosis and management of patients with hereditary anemias

et al. 2018

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Mutations in more than 70 genes cause hereditary anemias (HA), a highly heterogeneous group of rare/low frequency disorders in which we included: hyporegenerative anemias, as congenital dyserythropoietic anemia (CDA) and Diamond-Blackfan anemia; hemolytic anemias due to erythrocyte membrane defects, as hereditary spherocytosis and stomatocytosis; hemolytic anemias due to enzymatic defects. The study describes the diagnostic workflow for HA, based on the development of two consecutive versions of a targeted-NGS panel, including 34 and 71 genes, respectively. Seventy-four probands from 62 unrelated families were investigated. Our study includes the most comprehensive gene set for these anemias and the largest cohort of patients described so far. We obtained an overall diagnostic yield of 64.9%. Despite 54.2% of cases showed conclusive diagnosis fitting well to the clinical suspicion, the multi-gene analysis modified the original clinical diagnosis in 45.8% of patients (nonmatched phenotype-genotype). Of note, 81.8% of nonmatched patients were clinically suspected to suffer from CDA. Particularly, 45.5% of the probands originally classified as CDA exhibited a conclusive diagnosis of chronic anemia due to enzymatic defects, mainly due to mutations in PKLR gene. Interestingly, we also identified a syndromic CDA patient with mild anemia and epilepsy, showing a homozygous mutation in CAD gene, recently associated to early infantile epileptic encephalopathy-50 and CDA-like anemia. Finally, we described a patient showing marked iron overload due to the coinheritance of PIEZO1 and SEC23B mutations, demonstrating that the multi-gene approach is valuable not only for achieving a correct and definitive diagnosis, but also for guiding treatment.

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G6PD deficiency assessment in Freetown, Sierra Leone, reveals further insight into the molecular heterogeneity of G6PD A-

Abstract: Glucose-6-phosphate dehydrogenase (G6PD) deficiency in Africa is of high prevalence, although precise data are lacking in many individual nations. We investigated 129 unrelated subjects (71 male subjects, 58 female

Cited by 15 publications

References 12 publications

Glucose-6-Phosphate Dehydrogenase: Update and Analysis of New Mutations around the World

Glucose-6-Phosphate Dehydrogenase: Update and Analysis of New Mutations around the World

Glucose-6-Phosphate Dehydrogenase Deficiency A− Variant in Febrile Patients in Haiti

Multi‐gene panel testing improves diagnosis and management of patients with hereditary anemias

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