Molecular characterization of G6PD deficiency in Southern Italy: heterogeneity, correlation genotype–phenotype and description of a new variant (G6PD Neapolis)

Alfinito, Fiorella; Cimmino, Amelia; Ferraro, Filomena; Cubellis, Maria Vittoria; Vitagliano, Luigii; Francese, Matteo; Zagari, Adriana; Rotoli, B.; Filosa, Stefania; Martini, Giuseppe

doi:10.1046/j.1365-2141.1997.1512967.x

Cited by 12 publications

(9 citation statements)

References 17 publications

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“…Of the nine subjects we identified with this mutation, seven had favism-acute hemolysis following the ingestion of fava beans-while nobody have had chronic hemolysis. Thus far, G6PD Cosenza has been described in different parts of Italy (Calabro et al 1993;Cappellini et al 1996;Alfinito et al 1997;Martinez di Montemuros et al 1997) and in Iran (Mesbah-Namin et al 2002), but its prevalence was rather low at around 2% and 7% of the deficient subjects, respectively. Here we report higher prevalence (37.5%) of G6PD Cosenza than anywhere else.…”

Section: Resultsmentioning

confidence: 99%

Characterization of G6PD deficiency in southern Croatia: description of a new variant, G6PD Split

et al. 2005

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Glucose-6-phosphate dehydrogenase (G6PD) deficiency protects from severe forms of malaria. It is interesting therefore to analyze the molecular basis underlying G6PD deficiency in regions such as the Mediterranean basin where malaria was present for a long time in history. Here we report on the genetic characterization of G6PD deficiency among inhabitants of one Mediterranean region-the Dalmatian region of south Croatia. We analyzed 24 unrelated G6PD-deficient male subjects. Molecular testing revealed several different mutations: G6PD Cosenza 9, G6PD Mediterranean 4, G6PD Seattle 3, G6PD Union 3, and G6PD Cassano 1. Furthermore, we have identified one novel G6PD variant that we named G6PD Split. This variant is caused by a nucleotide change 1442 C fi G leading to the amino acid substitution 481 Pro fi Arg and is characterized by moderate enzyme deficiency (class III variant). This study reveals a higher prevalence (37.5%) of the Cosenza mutation in the Dalmatian region than anywhere else previously investigated and overall shows the considerable molecular heterogeneity underlining G6PD deficiency that can be observed in Mediterranean populations.

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Section: Resultsmentioning

confidence: 99%

Characterization of G6PD deficiency in southern Croatia: description of a new variant, G6PD Split

et al. 2005

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“…The X-ray structure of line G6PD has been the template of choice to model its human homolog and, based on modeling, significant insights into G6PD's structurefunction relationships have been obtained [1,24,26,31 ]. However, residues located at the two mutation-rich clusters are among the least-alignable regions in the G6PD family, and especially for cluster A many of the charge residues are forced to be aligned with amino acids of a very different chemical nature between G6PD of human and G6PD of line (e.g.…”

Section: Structure-sequence Analysis Of G6pd Mutationsmentioning

confidence: 99%

“…As of August 1997, a total of 122 naturally occurring human G 6 P D mutants have been tabulated, of which about 90% arise from missense amino acid substitutions [34]. Structure-function analyses on this protein [1,24,26,31] have also been greatly facilitated by the determination of a G 6 P D X-ray structure from Leuconostoc mesenteroides (hereafter abbreviated as line) [29].…”

Section: Introductionmentioning

confidence: 99%

Amino acid conservation and clinical severity of human glucose-6-phosphate dehydrogenase mutations

1999

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More than a hundred naturally occurring mutations of human glucose-6-phosphate dehydrogenase (G6PD) have been identified at the amino acid level. The abundance of distinct mutation sites and their clinical manifestations make this enzyme ideal for structure-function analysis studies. We present here a sequence and structure combined analysis by which the severity of clinical symptoms resulting from point mutations of this enzyme is correlated with quantified degrees of amino acid conservation within 23 G6PD sequences from different organisms. Our analysis verifies, on a quantitative basis, a widely held notion that clinically severer mutations of G6PD usually occur at conserved amino acids. However, marked exceptions to this general trend exist which are most notably revealed by a number of mutations associated with chronic nonspherocytic hemolytic anemia (class I variants). When mapped onto a homology-derived structural model of human G6PD, these class I mutational sites of low amino acid conservation appear to localize in two spatially distinct clusters, both of which are populated with mutations consisting mainly of clinically severer variants (i.e. class I and class II). These results of computer-assisted analyses contribute to a further understanding of the structure-function relationships of human G6PD deficiency.

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“…The X-ray structure of lme G6PD has been the template of choice to model its human homolog and, based on modeling, significant insights into G6PD's structurefunction relationships have been obtained [1,24,26,31]. However, residues located at the two mutation-rich clusters are among the least-alignable regions in the G6PD family, and especially for cluster A many of the charge residues are forced to be aligned with amino acids of a very different chemical nature between G6PD of human and G6PD of lme (e.g.…”

Section: Class I Mutants With Low Amino Acid Conservation and Two Mutmentioning

confidence: 99%

“…As of August 1997, a total of 122 naturally occurring human G6PD mutants have been tabulated, of which about 90% arise from missense amino acid substitutions [34]. Structure-function analyses on this protein [1,24,26,31] have also been greatly facilitated by the determination of a G6PD X-ray structure from Leuconostoc mesenteroides (hereafter abbreviated as lme) [29].…”

Section: Introductionmentioning

confidence: 99%

Amino Acid Conservation and Clinical Severity of Human Glucose-6-Phosphate Dehydrogenase Mutations

Cheng¹,

Tang²,

Hwang³

1999

J Biomed Sci

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More than a hundred naturally occurring mutations of human glucose-6-phosphate dehydrogenase (G6PD) have been identified at the amino acid level. The abundance of distinct mutation sites and their clinical manifestations make this enzyme ideal for structure-function analysis studies. We present here a sequence and structure combined analysis by which the severity of clinical symptoms resulting from point mutations of this enzyme is correlated with quantified degrees of amino acid conservation within 23 G6PD sequences from different organisms. Our analysis verifies, on a quantitative basis, a widely held notion that clinically severer mutations of G6PD usually occur at conserved amino acids. However, marked exceptions to this general trend exist which are most notably revealed by a number of mutations associated with chronic nonspherocytic hemolytic anemia (class I variants). When mapped onto a homology-de- rived structural model of human G6PD, these class I mutational sites of low amino acid conservation appear to localize in two spatially distinct clusters, both of which are populated with mutations consisting mainly of clinically severer variants (i.e. class I and class II). These results of computer-assisted analyses contribute to a further understanding of the structure-function relationships of human G6PD deficiency.

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Molecular characterization of G6PD deficiency in Southern Italy: heterogeneity, correlation genotype–phenotype and description of a new variant (G6PD Neapolis)

Cited by 12 publications

References 17 publications

Characterization of G6PD deficiency in southern Croatia: description of a new variant, G6PD Split

Characterization of G6PD deficiency in southern Croatia: description of a new variant, G6PD Split

Amino acid conservation and clinical severity of human glucose-6-phosphate dehydrogenase mutations

Amino Acid Conservation and Clinical Severity of Human Glucose-6-Phosphate Dehydrogenase Mutations

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