A novel point mutation in a class IV glucose-6-phosphate dehydrogenase variant (G6PD São Paulo) and polymorphic G6PD variants in São Paulo State, Brazil

Abstract

In this study, we used red cell glucose-6-phosphate dehydrogenase (G6PD) activity to screen for G6PD-deficient individuals in 373 unrelated asymptomatic adult men who were working with insecticides (organophosphorus and carbamate) in dengue prevention programs in 27 cities in São Paulo State, Brazil. Twenty-one unrelated male children suspected of having erythroenzymopathy who were attended at hospitals in São Paulo city were also studied. Fifteen of the 373 adults and 12 of the 21 children were G6PD deficient. G6PD gene mutations were investigated in these G6PD-deficient individuals by using PCR-RFLP, PCR-SSCP analysis and DNA sequencing. Twelve G6PD A-202A/376G and two G6PD Seattle844C, as well as a new variant identified as G6PD São Paulo, were detected among adults, and 11 G6PD A-202A/376G and one G6PD Seattle844C were found among children. The novel mutation c.660C > G caused the replacement of isoleucine by methionine (I220M) in a region near the dimer interface of the molecule. The conservative nature of this mutation (substitution of a nonpolar aliphatic amino acid for another one) could explain why there was no corresponding change in the loss of G6PD activity (64.5% of normal activity in both cases).

Genetic Profiles of Korean Patients With Glucose-6-Phosphate Dehydrogenase Deficiency

“…Since 1999, when G6PD Riley was reported at our institute, seven G6PD mutation types have been identified in Korea. The same mutations have also been found in Brazil (G6PD São Paulo) [18], Poland (G6PD Seoul) [26], Americas (G6PD Riley) [21], Mexico (G6PD Guadalajara) [20], and Japan (G6PD Tokyo) [19]. In addition, several mutations can occur at the same nucleotide position, but result in different amino acid changes in different ethnic populations.…”

“…Among the seven mutations, five were identified at our institute; one novel mutation (p.Cys385Gly named as G6PD Kangnam) and two known mutations (p.Ile220Met [G6PD São Paulo] [18] and p.Glu416Lys [G6PD Tokyo] [19]) were newly identified in the Korean population in this study. Two known mutations (p.Arg387Cys [G6PD Guadalajara] [20] and p.Ile380Thr [G6PD Riley] [21]) were reported previously by other researchers [34] at our institute.…”

“…The G6PD enzyme level increased to 10.5 U/g Hb, and the G6PD deficiency was categorized as Class IV according to the WHO classification. Sanger sequencing of the G6PD revealed a c.660C>G (p.Ile220Met) mutation, which was previously reported as G6PD São Paulo [18]. …”

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

“…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.…”

“…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). It is interesting to note that this mutation was detected among adults.…”