Glucose 6‐phosphate dehydrogenase Palermo R257M: a novel variant associated with chronic non‐spherocytic haemolytic anaemia

Rigano, Paolo; Fabiano, Carmelo; Pojero, Fannj; Niceta, Marcello; Pecoraro, A.; Maggio, Aurelio; Sammarco, P.

doi:10.1111/j.1365-2141.2009.08044.x

Cited by 4 publications

(4 citation statements)

References 7 publications

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“…Outside of exon 10, some other examples of mutations that lead to CNSHA include G6PD Zacatecas (c.770G > T) and G6PD Palermo (c.769C > A, c.770G > T), reported by Vaca et al ( 80 ) and Rigano et al ( 87 ). Both mutations are in exon 7 of the G6PD gene.…”

Section: Glucose-6-phosphate Dehydrogenase Activity In Relation To Ge...mentioning

confidence: 97%

Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Hyperbilirubinemia: Insights on Pathophysiology, Diagnosis, and Gene Variants in Disease Heterogeneity

et al. 2022

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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a prevalent condition worldwide and is caused by loss-of-function mutations in the G6PD gene. Individuals with deficiency are more susceptible to oxidative stress which leads to the classical, acute hemolytic anemia (favism). However, G6PD deficiency in newborn infants presents with an increased risk of hyperbilirubinemia, that may rapidly escalate to result in bilirubin induced neurologic dysfunction (BIND). Often with no overt signs of hemolysis, G6PD deficiency in the neonatal period appears to be different in the pathophysiology from favism. This review discusses and compares the mechanistic pathways involved in these two clinical presentations of this enzyme disorder. In contrast to the membrane disruption of red blood cells and Heinz bodies formation in favism, G6PD deficiency causing jaundice is perhaps attributed to the disruption of oxidant-antioxidant balance, impaired recycling of peroxiredoxin 2, thus affecting bilirubin clearance. Screening for G6PD deficiency and close monitoring of affected infants are important aspects in neonatal care to prevent kernicterus, a permanent and devastating neurological damage. WHO recommends screening for G6PD activity of all infants in countries with high prevalence of this deficiency. The traditional fluorescent spot test as a screening tool, although low in cost, misses a significant proportion of cases with moderate deficiency or the partially deficient, heterozygote females. Some newer and emerging laboratory tests and diagnostic methods will be discussed while developments in genomics and proteomics contribute to increasing studies that spatially profile genetic mutations within the protein structure that could predict their functional and structural effects. In this review, several known variants of G6PD are highlighted based on the location of the mutation and amino acid replacement. These could provide insights on why some variants may cause a higher degree of phenotypic severity compared to others. Further studies are needed to elucidate the predisposition of some variants toward certain clinical manifestations, particularly neonatal hyperbilirubinemia, and how some variants increase in severity when co-inherited with other blood- or bilirubin-related genetic disorders.

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Section: Glucose-6-phosphate Dehydrogenase Activity In Relation To Ge...mentioning

confidence: 97%

Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Hyperbilirubinemia: Insights on Pathophysiology, Diagnosis, and Gene Variants in Disease Heterogeneity

et al. 2022

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“…Taking account these new variants included in this review, the number of reported G6PD mutations is 217, being as follows: 182 (83.9%) are single nucleotide substitutions (missense variants), 19 (8.7%) are multiple mutations (two or more substitutions), 11 (5.1%) are deletions, and five (2.3%) mutations affect the introns. Interestingly, we found 16 mutations corresponding to single nucleotide substitutions (missense variants) that were previously reported before in Minucchi’s review [34] and that were not considered as the G6PD Class I mutants: Zacatecas (Arg257Leu; exon 7) [37], Palermo (Arg257Met, exon 7) [38], Hamburg (Pro276Leu, exon 8) [39], Veracruz (Arg365His, exon 10) [37], Yucatan (Lys429Glu, exon 10) [37], Tennessee (Leu422Val, exon 10) [40], and one deletion named G6PD Taif (174Gly, exon 6) [41] (Table 1). …”

Section: Molecular Characterization Of G6pd Variantsmentioning

confidence: 99%

“…G6PD Palermo mutation presents a transversion of the nucleotides C769A and G770T in exon 7 and replaces arginine for methionine in codon 257, which may lead to changes in the protein structure causing chronic hemolytic anemia [38] (Figure 4). Kordes et al [39] reported the Class I G6PD Hamburg mutant involving a substitution of cytocine for thymine (C > T) at nucleotide 827 (exon 8) (Pro276Leu) and was detected in a Caucasian neonate with chronic nonspherocytic hemolytic anemia (Figure 4).…”

Section: Molecular Characterization Of G6pd Variantsmentioning

confidence: 99%

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

Gómez-Manzo

Marcial-Quino

Vanoye-Carlo

et al. 2016

IJMS

161

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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“…These include certain food items, therapeutic drugs, infections, and exposure to chemicals (e.g. hair dye containing naphthol) [19,22,37,55]. G6PD variants have been classified into five WHO categories according to the severity of clinical manifestation resulting from the genotype (see Table 1), with classes II and III being the most common type of polymorphic G6PD-deficient variant [23,33].…”

Section: G6pd As An Important Pharmacogenementioning

confidence: 99%

PharmGKB summary

McDonagh¹,

Thorn²,

Bautista

et al. 2012

Pharmacogenetics and Genomics

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Glucose 6‐phosphate dehydrogenase Palermo R257M: a novel variant associated with chronic non‐spherocytic haemolytic anaemia

Cited by 4 publications

References 7 publications

Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Hyperbilirubinemia: Insights on Pathophysiology, Diagnosis, and Gene Variants in Disease Heterogeneity

Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Hyperbilirubinemia: Insights on Pathophysiology, Diagnosis, and Gene Variants in Disease Heterogeneity

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

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