6 dez. O estudo compreendeu a avaliação da deficiência de GlicoseFosfato Desidrogenase (G6PD) e perfil hematológico em indivíduos ( Glucosephosphatase dehydrogenase (G6PD) deficiency is the most common enzyme deficiency in humans, affecting million people. La deficiència de G6PD està estretament relacionada amb el favisme, un trastorn que es caracteritza per una reacció hemolítica al consum de faves. El nom de.

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Because this pathway is the only NADPH-generation process in mature red cells, which lack the citric acid cycle, a genetic deficiency of G6PD is often associated with adverse physiologic effects summary by Takizawa et al. The deduced amino acid protein has a molecular mass of 58 kD.

G6PD deficiency in Latin America: systematic review on prevalence and variants

Cappellini and Fiorelli stated that the G6PD protein contains amino acids. The protein-coding region is divided into 12 segments, ranging from 12 to bp, and an intron is present in the 5-prime untranslated region. The major 5-prime end of mature G6PD mRNA in several cell lines is deficienciia bp upstream of the translation-initiating codon.

Comparison of the ee region of G6PD and 10 other housekeeping enzyme genes confirmed the presence of common features. In particular, in 8 cases in which a ‘TATA’ box was present, a conserved sequence of 25 bp was seen immediately downstream.

Incidence evaluation of GlucosePhosphate Dehydrogenase and hematological profile in Rondonia

The region included a prominent CpG island, starting about nucleotides upstream of the transcription initiation site, extending about 1, nucleotides downstream of the initiation site, and ending at the start of the first intron. The transcribed region from the initiation site to the poly A addition site covered 15, bp. The sequence of the 13 exons agreed with the published cDNA sequence and, for the 11 exons tested, with the corresponding sequence in a yeast artificial chromosome YAC.

Four were outside the borders of the mRNA transcript of the gene; all of the others were found in a large 9, bp intron between exons 2 and 3. The Japanese pufferfish Fugu rubripes is a useful model for the comparative study of vertebrate genomes because of the compact nature of its genome.

Since the Fugu genome is approximately 8 times smaller than that of mammals, most genes should be more compact. To test this hypothesis, Mason et al. Intron 2 is also the largest intron in both species. However, they found that the Fugu gene was 4 times smaller than the human gene; the difference was accounted for by the fact that the pufferfish gene has smaller introns.

The sequences fell in the expected arrangement based on established phylogenetic relationships, with the Plasmodium falciparum sequence diverging most widely. The genes share a conserved promoter region that has bidirectional housekeeping activity.

From the alignment of the amino acid sequence of 52 G6PD species from 42 different organisms, they found a striking correlation between the amino acid replacements that cause G6PD deficiency in humans and the sequence conservation of G6PD. The findings were considered consistent with the notion that all human mutants have residual enzyme activity and that null mutations are lethal at some stage of development. Comparing the distribution of mutations in the human housekeeping gene with evolutionary conservation is a useful tool for pinpointing amino acid residues important for the stability or the function of the corresponding protein.

From study of radiation-induced segregants irradiated human cells ‘rescued’ by fusion with hamster cellsGoss and Harris showed that the order of 4 loci on the X chromosome is PGK: G6PD and that the 3 intervals between these 4 loci are, in relative terms, 0.

Studying X-autosome translocations in somatic cell hybrids, Pai et al. G6PD is distally situated at Xq The level of lactate dehydrogenase was the same. Epstein’s conclusion was that the G6PD gene is X-linked in the mouse, that synthesis occurs in the oocyte and is dosage-dependent, and that X inactivation does not occur in oocytes. They were prompted to undertake these studies because of patients with symptoms such as myalgia, cramps, and muscle weakness under conditions of stress, particularly physical exertion.


All 3 variants–Mediterranean A statistically significant relationship was found in the activity of G6PD in erythrocytes and muscle of male subjects. The results suggested to the authors that, for a given variant, the extent of the enzyme defect in muscle can be determined from the G6PD activity of erythrocytes, using an equation that they derived.

In studies in bovine aortic and human coronary artery endothelial cells, Leopold et al. In vivo aldosterone infusion in mice decreased vascular G6PD expression and impaired vascular reactivity; these effects were abrogated by spironolactone or vascular gene transfer of G6pd.

The variety of forms of the G6PD enzyme is great Yoshida et al. The World Health Organization WHOgave its attention to problems of nomenclature and standard procedures for study.

The demonstrated polymorphism at this X-linked locus rivals that of the autosomal loci for the polypeptide chains of hemoglobin. As g6pc the latter instance, single amino acid substitution has been demonstrated as the basis of the change in the G6PD molecule resulting from mutation Yoshida et al. The G6PD variants have been divided into 5 classes according to the level of enzyme activity: Mutations causing nonspherocytic hemolytic anemia are clustered near the carboxy end of the enzyme, in the region between amino acids andwhereas most of the clinically mild mutations are located at the amino end of the molecule.

As the intragenic defects have been identified, many variants that were thought to be unique have been found to be identical on sequence analysis. This finding should not be surprising inasmuch as deficciencia methods of biochemical characterization are not very accurate, particularly when dealing with mutant enzymes that are unstable.


The frequencies of low-activity alleles of G6PD in humans are highly correlated with the prevalence of malaria see These deficiency alleles are thought to provide reduced risk for infection by the Plasmodium g6dp and are maintained at high frequency despite the illnesses that they cause.

Haplotype analysis of A- That resistance to severe malaria is the basis of the high frequency of G6PD deficiency and that both hemizygotes and heterozygotes enjoy an advantage was established by Ruwando et al. A mathematical model incorporating the measured selective advantage against malaria suggested that a counterbalancing selective disadvantage, associated with this enzyme deficiency, has retarded its rise in frequency in malaria-endemic regions.

They provided a useful map of 19 sporadic G6PD variants found in Italy. They deficienciaa to regions where the common forms of G6PD deficiency are frequent. Hitzeroth and Bender found an increasing frequency of apparent BB homozygotes with increasing age of groups of South African blacks studied.

They suggested that this represents selection against A- cell lines in heterozygotes and speculated further that malaria is the underlying selective agent. Mohrenweiser and Neel identified thermolabile variants of lactate dehydrogenase Dwficiencia, glucosephosphate isomerase, and glucosephosphate dehydrogenase.

None was detectable as a variant by standard electrophoretic techniques. Beutler hypothesized that the marked differences deficiecia the extent to which various tissues manifest the deficiency state in various enzymopathies including G6PD deficiency may be related to tissue-to-tissue differences in proteases.

Mutation may produce changes in susceptibility of the enzyme to proteases. edficiencia

Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei The other 6 mutants were all associated with enzyme deficiency. Single point mutations were identified in G6PD Mediterranean By use of 14 unique sequence probes deficjencia 18 restriction enzymes, D’Urso et al. A PstI site that maps to exon 10 was monomorphic in all British and Italian subjects studied, but was polymorphic in West African people. By sequence analysis, D’Urso et al. No amino acid change was produced in the protein.

It has been found that even in the same population, more than 1 G6PD variant is present. For example, in the island of Sardinia, extensive clinical and biochemical studies identified 4 different G6PD variants. De Vita et al.

The other 3 ve were accompanied by very severe G6PD deficiency. This is the same change as that in G6PD Mediterranean These 3 Sardinian variants also had a silent mutation in exon 11 with a change of TAC-to-TAT, both of which encode tyrosine at amino acid These findings indicate that some G6PD-deficient variants identified only on the basis of their biochemical characteristics may not correspond to different mutations in the G6PD gene.


Deficiència de glucosa-6-fosfat-deshidrogenasa

The variations may be due to posttranscriptional or posttranslational modifications of the enzyme; whether the modifications are due to mutations in a tightly linked gene or to noninherited 6gpd changes could not be distinguished with the data available.

Study of families in which different forms of G6PD Mediterranean segregate suggested that the biochemical characteristics are transmitted in the family along with dficiencia enzyme deficiency, thus favoring the first hypothesis. In a study of an unselected sample of 1, schoolboys from the province of Matera Lucania in southern Italy, Calabro et al.

The overall rate of G6PD deficiency was 2. The frequency ranged from 7. They concluded from these and their previous studies that G6PD B is the most ancient genotype. Dw nucleotide mutation, with its worldwide distribution, probably occurred next. Among the 43 samples, they identified 5 different nucleotide substitutions: The 5 substitutions accounted for 36 of the 43 samples; none of these substitutions had been reported in non-Asians.

The substitutions at nucleotides and were new findings. The substitutions at nucleotides and accounted for over one-half of the samples.

The mutations were almost exclusively missense mutations, causing single amino acid substitutions. They were spread throughout the coding region of the gene, although there g6ppd to be a clustering of mutations deficienncia caused a more severe clinical phenotype towards the 3-prime end of the gene. The absence of large deletions, frameshift mutations, and nonsense mutations was considered consistent with the notion that a total lack of G6PD activity would be lethal.

Miwa and Fujii listed the deficienciaa responsible for about 78 G6PD variants. Mason reviewed information on the G6PD enzyme and on mutations in the gene. A map of amino acids showing the location of mutations, including double mutations, was provided.

In erythroid, myeloid, and lymphoid cell lineages there was a significant excess of G6PD-normal cells, suggesting that a selective mechanism operates at the level of pluripotent blood stem cells. They concluded that their studies provided evidence that severe G6PD deficiency adversely affects the proliferation or survival of nucleated blood cells.

They demonstrated a significant sex difference in allele frequencies in African Americans but not in Caucasians, and linkage disequilibrium for the p55 and G6PD alleles in Caucasians but not in African Americans.

In 11 cases, the mutation they found had previously been reported in unrelated individuals. These mutations comprised 7 different missense mutations and re bp deletion, G6PD Nara Repeated findings of the same mutations suggest that a limited number of amino acid changes can produce the chronic nonspherocytic hemolytic anemia phenotype and be compatible with normal development. They found 1 new mutation, G6PD Serres The relational database integrates up-to-date mutational and structural defiiciencia from various databanks with biochemically characterized variants and their associated phenotypes obtained from published literature and a Favism website.

The variants included Cosenza The variants in 3 patients Although none of the individuals had molecular evidence of malaria infection, the findings suggested that malaria endemics had occurred in the past and that G6PD deficiency has been maintained as an advantageous genetic trait in this population.

At least 5 different G6PD variants were identified, suggesting that several Asian ethnic groups, such as Burmese, Laotian, Cambodian, Thai, and Chinese, participated in establishing the current ethnic identity of the population of Phuket.

The variants varied in frequency across the ethnic groups and defiiencia geographically with historical patterns of malaria. The variants were different from those reported in African, European, and Indian populations.

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