Genetic Mutation Characteristics of Glucose-6-Phosphate Dehydrogenase Deficiency Patients in Wuhan / 中国实验血液学杂志

OBJECTIVE@#To explore the genotype mutation characteristics of patients with glucose-6-phosphate dehydrogenase(G6PD) deficiency in Wuhan.@*METHODS@#A total of 1 321 neonates with positive screening and outpatients were received G6PD mutation detection, 12 kinds of common G6PD mutation in Chinese people was detected by using multicolor melting curve analysis (MMCA) method, for those with negative results, the enzyme activity and clinical information were analyzed, sequencing was recommended after informed consent when it is necessary.@*RESULTS@#Among 1321 patients, a total of 768 mutations were detected out, with a detection rate of 58.1%. A total of 18 types of G6PD genotypes were identified, including c.1388G>A, c.1376G>T, c.95G>A, c.1024C>T, c.871G>A, c.392G>T, c.487G>A, c.1360C>T, c.1004C>A, c.517T>C, c.592C>T, c.94C>G, c.152C>T, c.320A>G, c.1028A>G, c.1316G>A, c.1327G>C and c.1376G>C, including 683 male hemizygotes, 3 female homozygotes, 80 female heterozygotes and 2 female compound heterozygous.@*CONCLUSION@#A total of 18 types of G6PD mutations are identified in the reaserch, and c.94C>G, c.1028A>G and c.1327G>C are first reported in Chinese population. The most common G6PD mutation types in Wuhan are c.1388G>A, c.1376G>T, c.95G>A.

Screening results and genetic features of glucose-6-phosphate dehydrogenase deficiency in 54 025 preterm infants in Chengdu, China / 中国当代儿科杂志

OBJECTIVE@#To analyze the screening results of glucose-6-phosphate dehydrogenase (G6PD) deficiency and gene mutation distribution of G6PD deficiency in preterm infants in Chengdu, China, in order to provide a basis for the improvement of G6PD screening process in preterm infants.@*METHODS@#Fluorescent spot test for G6PD deficiency using dried blood spots was used for G6PD screening of 54 025 preterm infants born from January 1, 2015 to December 31, 2019 in Chengdu, and G6PD enzymology and gene detection were used for the diagnosis of 213 infants with positive screening results.@*RESULTS@#Among the 54 025 preterm infants, 192 were diagnosed with G6PD deficiency, with an incidence rate of 3.55‰. The incidence rate of G6PD deficiency in preterm infants was higher than that in full-term infants in the same period of time and tended to increase year by year. Birth in summer, gestational age T mutation tend to have mild conditions.

Prevalence of G6PD deficiency and molecular characterization of G202A, A376G and C563T polymorphisms in newborns in Southeastern Brazil / Prevalência da deficiência de G6PD e caracterização molecular dos polimorfismos G202A, A376G e C563T em neonatos no Sudeste do Brasil

ABSTRACT Objective To evaluate the prevalence of G6PD deficiency and characterize G202A, A376G and C563T polymorphisms in neonates using molecular assays. Methods A total of one thousand samples were tested through quantitative analysis of enzyme activity, detecting 25 G6PD-deficient individuals. Patients identified as deficient were submitted to molecular analysis quantitative real-time polymerase chain reaction - (qPCR) to investigate the presence of variants associated with the deficiency. Results The total prevalence of G6PD deficient was 2.5%. Of the 25 samples identified as deficient, 21 were submitted to qPCR assay to analyze the presence of G202A, A376G and C563T variants. All samples showed the G202A/A376G genotype, characterizing G6PD A- phenotype. Conclusion The prevalence of G6PD deficiency in the present study was similar to that observed in other study populations in Brazil. Molecular analysis identified in all patients the presence of the genetic polymorphism G202A/A376G, more common in the Brazilian population with G6PD deficiency, which is directly estimated by enzyme activity level.

RESUMO Objetivo Avaliar a prevalência da deficiência de G6PD e caracterizar, por ensaios moleculares, os polimorfismos G202A, A376G e C563T em recém-nascidos. Métodos Foram testadas mil amostras por meio da análise quantitativa da atividade enzimática, detectando 25 portadores de deficiência de G6PD. Os pacientes identificados como deficientes foram submetidos à análise molecular reação em cadeia da polimerase em tempo real (qPCR) para pesquisa da presença das variantes associadas à deficiência. Resultados A prevalência total de deficientes de G6PD foi de 2,5%. Das 25 amostras identificadas como deficientes, 21 foram submetidas ao qPCR, para análise da presença das variantes G202A, A376G e C563T. Todas as amostras apresentaram o genótipo G202A/A376G, caracterizando fenótipo G6PD A-. Conclusão A prevalência da deficiência da G6PD no presente estudo foi semelhante à verificada em outras populações de estudo no Brasil. A análise molecular identificou em todos os pacientes a presença do polimorfismo genético G202A/A376G, mais comum na população brasileira portadora da deficiência de G6PD, que é diretamente estimada pelo nível de atividade enzimática.

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

BACKGROUND: We describe the genetic profiles of Korean patients with glucose-6-phosphate dehydrogenase (G6PD) deficiencies and the effects of G6PD mutations on protein stability and enzyme activity on the basis of in silico analysis. METHODS: In parallel with a genetic analysis, the pathogenicity of G6PD mutations detected in Korean patients was predicted in silico. The simulated effects of G6PD mutations were compared to the WHO classes based on G6PD enzyme activity. Four previously reported mutations and three newly diagnosed patients with missense mutations were estimated. RESULTS: One novel mutation (p.Cys385Gly, labeled G6PD Kangnam) and two known mutations [p.Ile220Met (G6PD São Paulo) and p.Glu416Lys (G6PD Tokyo)] were identified in this study. G6PD mutations identified in Koreans were also found in Brazil (G6PD São Paulo), Poland (G6PD Seoul), United States of America (G6PD Riley), Mexico (G6PD Guadalajara), and Japan (G6PD Tokyo). Several mutations occurred at the same nucleotide, but resulted in different amino acid residue changes in different ethnic populations (p.Ile380 variant, G6PD Calvo Mackenna; p.Cys385 variants, Tomah, Madrid, Lynwood; p.Arg387 variant, Beverly Hills; p.Pro396 variant, Bari; and p.Pro396Ala in India). On the basis of the in silico analysis, Class I or II mutations were predicted to be highly deleterious, and the effects of one Class IV mutation were equivocal. CONCLUSIONS: The genetic profiles of Korean individuals with G6PD mutations indicated that the same mutations may have arisen by independent mutational events, and were not derived from shared ancestral mutations. The in silico analysis provided insight into the role of G6PD mutations in enzyme function and stability.

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

Plasmodium vivax radical cure requires the use of primaquine (PQ), a drug that induces haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals, which further hampers malaria control efforts. The aim of this work was to study the G6PDd prevalence and variants in Latin America (LA) and the Caribbean region. A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Low prevalence rates of G6PDd were documented in Argentina, Bolivia, Mexico, Peru and Uruguay, but studies from Curaçao, Ecuador, Jamaica, Saint Lucia, Suriname and Trinidad, as well as some surveys carried out in areas of Brazil, Colombia and Cuba, have shown a high prevalence (> 10%) of G6PDd. The G6PD A-202A mutation was the variant most broadly distributed across LA and was identified in 81.1% of the deficient individuals surveyed. G6PDd is a frequent phenomenon in LA, although certain Amerindian populations may not be affected, suggesting that PQ could be safely used in these specific populations. Population-wide use of PQ as part of malaria elimination strategies in LA cannot be supported unless a rapid, accurate and field-deployable G6PDd diagnostic test is made available.

Deficiencia de glucosa-6-fosfato deshidrogenasa en recién nacidos en Argentina / Glucose-6-phosphate dehydrogenase deficiency in newborns in Argentina / Deficiência de glicose-6-fosfato desidrogenase em recém-nascidos na Argentina

En Argentina la pesquisa neonatal es obligatoria por ley para ciertas condiciones, pero no para la deficiencia de Glucosa-6-Fosfato Deshidrogenasa (G6PD). La deficiencia de G6PD es un trastorno ligado al cromosoma X que puede causar ictericia neonatal, eventualmente kernicterus y hemólisis intravascular aguda en asociación a la exposición a sustancias oxidantes, la ingestión de ciertos alimentos, drogas o medicamentos, algunas infecciones, o cualquier otra situación que implique estrés celular. Es una de las enzimopatías más frecuentes en todo el mundo. El objetivo de este estudio fue determinar la prevalencia de la deficiencia de G6PD en Argentina. Se analizaron 4.500 muestras de sangre seca en varones recién nacidos provenientes de diferentes regiones del país. La actividad de la enzima se determinó cuantitativamente mediante un método fluorométrico semiautomatizado desarrollado en el laboratorio específico para la medición del NADPH producido. El mismo fue evaluado frente a un método comercial. Se hallaron 13 (0,29%) niños que expresaron deficiencia total y 33 (0,73%) deficiencia parcial. Este hallazgo demuestra que la deficiencia de G6PD es una condición frecuente, la detección es factible y no sólo sería útil para la atención especializada contra hemólisis severa en el neonato, sino también para tomar otras medidas preventivas en la edad adulta.

In Argentina, newborn screening is mandatory by law for certain conditions, but not for Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency. G6PD deficiency is an X chromosome-linked disorder which causes, in most cases, neonatal jaundice, and even kernicterus and acute intravascular hemolysis in association with exposure to oxidizing substances, ingestion of certain foods, drugs or medications, some infections, or any other situation involving cellular stress. It is one of the most common enzymopathies in the world. The aim of this study was to determine the prevalence of G6PDH deficiency in Argentina. A total of 4.500 newborn male dried blood samples from different regions of the country were analyzed. The activity of the enzyme was quantitatively determined by an "in house" developed fluorometric method, measuring the rate of formation of NADPH. It was evaluated against a commercial method. A total of 13 (0.29%) children expressing total deficiency were found, while 33 (0.73%) demonstrated intermediate deficiency. This finding is important as such patients must receive a preventive and educational care. Screening for G6PDH deficiency is feasible and not only would it take early preventive measures against severe hemolysis in the neonatal period, but also other preventive measures later in life.

Na Argentina, a pesquisa neonatal é obrigatória por lei para determinadas condições, mas não para a deficiência de glicose-6-fosfato desidrogenase (G6PD). Deficiência de G6PD é um distúrbio ligado ao cromossomo X que pode provocar icterícia neonatal, kernicterus e hemólise intravascular aguda em associação com a exposição a substâncias oxidantes, a ingestão de certos alimentos, drogas ou medicamentos, algumas infecções, ou qualquer outra situação que envolva estresse celular. É uma das enzimopatias mais frequentes em todo o mundo. O objetivo deste estudo foi determinar a prevalência de deficiência de G6PDH na Argentina. Testamos 4.500 amostras de sangue seco de recém-nascidos do sexo masculino originários de diferentes regiões do país. A atividade da enzima foi determinada quantitativamente através de um método fluorimétrico semi-automatizado desenvolvido no laboratório específico para medir o NADPH produzido. O mesmo foi avaliado perante um método comercial. Acharam-se 13 (0,29%) crianças expressando deficiência total, enquanto que 33 (0,73%) demonstraram deficiência parcial. Este achado demonstra que a deficiência de G6PD é uma condição frequente, sua detecção é factível e não só seria útil para o atendimento especializado contra hemólise severa no neonato, mas também para tomar outras medidas preventivas na idade adulta.

Triagem neonatal de deficiência de glicose-6-fosfato desidrogenase e prevalência das mutações G202A (G6PD A-) e C563T (G6PD Mediterrâneo) em Mato Grosso/Brasil / Neonatal Screening for glucose-6-phosphate dehydrogenase deficiency and prevalence of G202A (G6PD A-) and C563T (G6PD mediterranean) mutations in Mato Grosso / Brazil

Objetivos: A deficiência de glicose-6-fosfato desidrogenase (G6PD) está associada a um maior risco de encefalopatia bilirrubínica e de crise hemolítica aguda grave desencadeada por drogas como a primaquina e a dapsona. Conhecer a prevalência dessa deficiência enzimática em área onde a malária e a hanseníase ainda estão presentes e conhecer a prevalência das principais mutações traz subsídios para planejamento de estratégias com vistas à redução de riscos associados a esta deficiência enzimática. Métodos: Estudo descritivo transversal conduzido em uma região do centro-oeste do Brasil. Exame de triagem para deficiência de G6PD foi realizado em 3573 recémnascidos. Exame confirmatório foi necessário em 188 crianças triadas como possíveis portadores de deficiência. Nas crianças em que foi confirmada a deficiência de G6PD foi feita pesquisa das mutações G202A (G6PD A-) e C563T (G6PD Mediterrâneo) por PCR. Resultados: A deficiência de G6PD foi confirmada em 63 crianças, sendo 60 meninos (95,2%) e três meninas (4,8%). O percentual de exames falso-positivos na fase de triagem foi de 66,5%, estando o percentual de falso-positivos associado à temperatura e tempo de transporte das amostras. Entre as crianças que confirmaram deficiência de G6PD, foi mais frequente a história de anemia em familiares e de icterícia neonatal. Houve associação entre hematócrito baixo e deficiência enzimática, mas não com hemoglobina, contagem de reticulócitos ou neutrófilos. A prevalência da deficiência de G6PD (IC95%) foi de 1,76% (1,37; 2,24) entre os recém-nascidos triados e de 3,34% entre os meninos (2,58; 4,25). A mutação C563T não foi identificada em nenhuma criança, mas a mutação G202A estava presente em 58 crianças - 92,06% (IC95%: 83,29 - 97,03): 56/60 meninos e em 2/3 meninas homozigotas. Foi identificado um menino com Kernicterus portador da mutação G202A em hemizigose. Conclusão: O elevado percentual de falso-positivos na etapa de triagem, o tempo necessário entre coleta...

Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with an increased risk of bilirubin encephalopathy in neonates and acute hemolytic crisis triggered by drugs such as primaquine and dapsone. In an area where malaria and Hansen's disease are still present, knowing the prevalence of this enzyme defect and determining the prevalence of major mutations is important for planning strategies for reducing the risks associated with this enzyme deficiency. Methods: Sectional study was conducted in a Midwestern region of Brazil. Screening for G6PD deficiency was performed in 3,573 neonates. Confirmatory tests were necessary for 188 positively screened children. After confirmation, PCR investigation was utilized to identify the mutations. Results: G6PD deficiency was confirmed in 63 children: 60 boys (95.2%) and 3 girls (4.8%). The percentage of false-positive cases in the screening phase, 66.5% and was associated with the temperature and transportation time of the samples. Family history of anemia and jaundice was more frequent among the children with confirmed G6PD deficiency. An association between a low hematocrit and enzyme deficiency was observed. However, there was no association with hemoglobin reticulocyte or neutrophils counts. The prevalence of G6PD deficiency (CI95%) was 1.76% (1.37; 2.24) among all screened neonates and 3.34% (2.58; 4.25) among male children. The C563T mutation was not identified in any child. The G202A mutation was present in 58 children - 92.06% (CI95%: 83.29 - 97.03), 56/60 boys and 2/3 homozygous girls. One boy with a hemizygous G202A mutation was identified as having Kernicterus. Conclusion: The high percentage of false-positive results when first screening for G6PD deficiency; the long delay time between the test and result; along with the high cost of the this screening test, are all factors that do not support adding this test to the already established Brazilian neonatal screening programs. The prevalence...

[Glucose 6-phosphate dehydrogenase deficiency in Tehran, Zanjan and Sistan-Balouchestan provinces: prevalence and frequency of Mediterranean variant of G6PD]

Glucose-6-phosphate dehydrogenase [G6PD] deficiency is an enzymopathy affecting about 400 million people worldwide. The distribution of G6PD deficiency and the molecular genetics of this enzyme vary widely among different ethnic groups. The aim of this study was to find out the frequency of G6PD deficiency and characterize the Mediterranean type mutation in deficient individuals in Turk, Balouch and Fars ethnic groups in Zanjan, Iranshahr and Tehran provinces. 1500 unrelated male individuals from Zanjan and 305 unrelated male students from Iranshahr were screened for G6PD deficiency by fluorescent spot test. Genomic DNA was extracted from deficient individuals and also from 64 G6PD deficient individuals from Tehran city. PCR was used to amplify flanking regions of exons 6 and 7 of this gene. The PCR products were digested by the MboII enzyme and electrophoresed on 3% agarose gel. Thirty-three [2.2%] individuals were shown to be deficient for G6PD from Zanjan population. Twenty-four out of 33 [72.8%] of the deficient individuals showed a mutation at nt 563 which is characteristic of Mediterranean type of mutation. Nine individuals were negative for this mutation. Fifty nine [19.3%] individuals of Iranshahr were shown to be deficient for G6PD. At the molecular level, 50 [85%] of the individuals showed Mediterranean type of mutation and 15% were negative for this mutation. Our results from Tehran showed that 47/64 [73.4%] of deficient individuals had Mediterranean type mutation and 26.6% were negative for this mutation. Despite different frequencies exist for deficiency of G6PD in Turk, Balouch and Fars populations, the results of the present study and others have shown that the predominant mutation of G6PD in Iran is of Mediterranean type

Prevalence and molecular identification of mediterranean glucose-6-phosphate dehydrogenase deficiency in Khuzestan Province, Iran

Glucose-6-phosphate dehydrogenase [G6Pd] deficiency is the most frequent genetic enzymatic disorder in human, which is inherited as an X-linked gene. It encodes a housekeeping enzyme, which is vital for cell survival. According to previous investigations, Mediterranean mutation [C563T] of g6pd gene is the most prevalent mutation in some provinces of Iran and neighboring countries. We aimed to study the Mediterranean mutation of g6pd gene in Khuzestan province of Iran. A total of 1064 randomly selected male blood samples were selected in Ahvaz, Khuzestan Province, in 2008 and screened for G6PD deficiency using fluorescent spot test method. In order to determine the frequency of G6PD Mediterranean variant, 144 G6PD deficient samples were analyzed by PCR-RFLP method. Eighty-one out of 1064 random selected screened samples were G6PD deficient, so a 7.6% frequency was obtained for G6PD deficiency. In addition, 105 out of 144 collected deficient samples had Mediterranean mutation that resulted in a 72.91% allel frequency. Corresponding to other investigations in Middle East countries and some provinces of Iran, we found that the Mediterranean mutation of g6pd gene was the most prevalent variant and G6PD deficiency occurred in a high frequency

Present status of understanding on the G6PD deficiency and natural selection.

G6PD deficiency is a common hemolytic genetic disorder, particularly in the areas endemic to malaria. Individuals are generally asymptomatic and hemolytic anemia occurs when some anti-malarial drugs or other oxidizing chemicals are administered. It has been proposed that G6PD deficiency provides protection against malaria. Maintaining of G6PD deficient alleles at polymorphic proportions is complicated because of the X-linked nature of G6PD deficiency. A comprehensive review of the literature on the hypothesis of malarial protection and the nature of the selection is being presented. Most of the epidemiological, in vitro and in vivo studies report selection for G6PD deficiency. Analysis of the G6PD gene also reveals that G6PD-deficient alleles show some signatures of selection. However, the question of how this polymorphism is being maintained remains unresolved because the selection/fitness coefficients for the different genotypes in the two sexes have not been established. Prevalence of G6PD deficiency in Indian caste and tribal populations and the different variants reported has also been reviewed.

DNA sequencing analysis of several G6PD variants previously defined by PCR-restriction enzyme analysis

Results of a corroborative DNA sequencing analysis for five glucose-6-phosphate dehydrogenase (G6PD) mutations previously defined by PCR-restriction enzyme analysis are presented. The suitability for performing DNA sequencing analysis is discussed along with the importance of selecting the proper PCR-REA strategy in order to define the presence of a specific mutation .

Glucose-6-phosphate dehydrogenase deficiency: molecular heterogeneity in southeast Asian countries.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in malaria endemic regions and is estimated to affect more than 400 million people worldwide. Deficient subjects are mostly asymptomatic but clinical manifestations range from neonatal jaundice due to acute hemolytic anemia to chronic non-spherocytic hemolytic anemia. To date, biochemical parameters allowed more than 400 different G6PD variants to be distinguished thereby suggesting a vast genetic heterogeneity. So far, only a small portion of this heterogeneity has been confirmed at the DNA level with the identification of about 90 different point mutations in the G6PD coding sequence. To determine the molecular background of G6PD deficiency in Southeast Asian countries, we conducted molecular analyses of G6PD patients from the Philippines, Malaysia, Singapore, Vietnam and Indonesia. The most prevalent mutation identified differs from country to country, thus suggesting independent mutational events of the G6PD gene.

G6PD Viangchan and G6PD Mediterranean are the main variants in G6PD deficiency in the Malay population of Malaysia.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked red blood cell enzymopathy common in malaria endemic areas. Individuals affected by this disease show a wide variety of clinical signs of acute hemolytic anemia. Mutations of the G6PD gene in the Malay population with G6PD deficiency in Kelantan, a state in North East Malaysia were studied. Ninety-three individuals with G6PD deficiency were subjected to mutation analysis of the G6PD gene using polymerase chain reaction based techniques of multiplex PCR. Of the ninety-three DNA samples studied, molecular defects were identified in 80 cases (86%). Variants were heterogeneous - 28.7% were found to have a G to A nucleotide change at nucleotide 871 of the G6PD gene (G871A), corresponding to G6PD Viangchan. The other major mutations were G6PD Mediterranean, G6PD Vanua Lava, G6PD Coimbra, G6PD Kaiping, G6PD Orissa, G6PD Mahidol, G6PD Canton and G6PD Chatham. These results showed that there are heterogeneous mutations of the G6PD gene associated with G6PD deficiency and that G6PD Viangchan and G6PD Mediterranean account for the main variants in G6PD deficiency among the Malay population in Malaysia.

Investigaçäo genético-epidemiológica e molecular da deficiência de G-6-PD em uma comunidade brasileira / G-6-PD deficiency in a Brazilian community: an investigation involving epidemiological genetics and molecular techniques

Teve por objetivo estudar a deficiência de G-6-PD em uma comunidade do interior do Estado de Säo Paulo (Bragança Paulista). Durante 36 meses foram selecionados 4.621 doadores de sangue do sexo masculino, detectando-se 80 deficientes em G-6-PD. A análise molecular foi realizada em 70 deficientes näo consangüíneios mediante a amplificaçäo de DNA por PCR seguida de digestäo por enzimas de restriçäo e análise de polimorfismo de conformaçäo em hélice simples (SSCP). Em 98,6 por cento dos casos, foi identificada a mutaçäo G-6-PD A- (202 G->A), por digestäo do exon 4 com Nla III. Verificou-se a presença de mutaçäo mais rara no exon 9, por SSCP. Näo foi constatado caso da variante Mediterrânea. Tais resultados mostraram que a variante A- (202->A), quase que exclusiva, foi introduzida na comunidade näo apenas por descedentes de africanos, como também pelos imigrantes italianos, espanhóis e portugueses. A contribuiçäo italiana em termos da variante Mediterrânea de G-6-PD foi menor do que a sua participaçäo em termos de talassemia beta, provavelmente devido à origem no Norte da Itália.

Epidemiologia molecular da variante A- da deficiência de G-6-PD no Estado de Säo Paulo / Molecular epidemiology of the A- G-6-PD variant in Säo Paulo State, Brazil

Os recentes avanços laboratoriais da biologia molecular permitiram o estudo de novos marcadores genéticos. No presente trabalho, investigamos a epidemiologia molecular da variante A- da deficiência de G-6-PD em uma populaçäo do estado de Säo Paulo. Material e métodos: Foram analisados molecularmente 60 homens paulistas näo-consangüineos (50 caucasóides e 10 negroídes), portadores da variante A- de G-6-PD. A caracterizaçäo molecular foi realizada pela digestäo dos exons 3 e 4 do gene da G-6-PD com a enzima de restriçäo NLa III. Resultados: Todos os indivíduos analisados revelaram a presença da mutaçäo A- 202 (G A). Discussäo: A populaçäo paulista é caracterizada por um alto grau de miscigenaçäo entre descendentes de europeus, principalmente de origens portuguesa, italiana e espanhola, e indivíduos de origem africana. Apesar dessa heterogenidade étnica, a mutaçäo A-202 (G A) foi a única introduzida nessa populaçäo. Esse resultado está de acordo com fluxo gênico no passado da variante A- de G-6-PD da Africa para a Europa. Conclusäo: Nossoa resultados indicam que a variante A- de G-6-PD está associada exclusivamente com a mutaçäo 202 (G A) no estado de Säo

Red cell enzymopathies as a model of inborn errors of metabolism.

The molecular abnormalities of erythroenzymopathies associated with hereditary hemolytic anemia have been determined using molecular techniques. Pyruvate kinase (PK) deficiency is the most common and well-characterized enzyme deficiency involving the glycolytic pathway and causing hereditary hemolytic anemia. We have identified six distinct missense mutations and a form of splicing mutation in 11 unrelated families with homozygous PK deficiency. Mutations located near the substrate binding site may change the conformation of the active site, resulting in a drastic loss of activity and severe clinical symptoms. Up to now, including these genetic defects, 21 missense, 1 nonsense and 2 splicing mutations, 2 insertions, and 3 deletions have been determined. G6PD deficiency is the most common metabolic disorder, and is associated with chronic and drug- or infection-induced hemolytic anemia. To date, sixty different mutations have now been identified. Except for three kinds of variants with small gene deletions or three nucleotide substitutions, all of those were found to be produced by one or two nucleotide substitutions. Molecular studies disclosed that all the class 1 variants associated with chronic hemolysis have the mutations surrounding either the substrate or the NADP binding site. Among rare enzymopathies, missense mutations have been determined in glucosephosphate isomerase deficiency, aldolase deficiency, triosephosphate isomerase (TPI) deficiency, phosphoglycerate kinase deficiency, and adenylate kinase deficiency. Compound heterozygous cases with missense mutation/nonsense mutation and missense mutation/decreased mRNA have been reported in TPI deficiency and diphosphoglyceromutase deficiency, respectively. In phosphofructokinase (PFK) deficiency, three kinds of 5'-splice junction mutations resulting in abnormally spliced PFK-M mRNA were identified. An exception is a hemolytic anemia due to increased adenosine deaminase activity. The basic abnormality appears to result from overproduction of structurally normal enzyme.

Genetic marker profile of primitive Kutia Kondh tribal population of Phulbani district (Orissa).

Blood samples from 330 Kutia Kondhs (a primitive tribal population of Orissa) were subjected to a battery of tests for genetic markers to find out the incidence of various blood group polymorphisms (ABO, MN, Duffy, JKa), serum proteins, sickling and G-6-PD deficiency. Predominance of O (39.09%) blood group for ABO, N blood group (53.44) for MN and Fya+b+ (55.72) for Duffy blood group, were observed. High incidence of Hp2-1 (39.33), SS (70.43) and CC (96.65) for haptoglobulin, C3 and transferrin respectively were seen. The overall frequency of sickling was observed to be 16.36 per cent. The sex-wise distribution of G-6-PD was 13.71 per cent for males and 1.84 for females.

Panorama de la deficiencia de la glucosa-6-fosfato deshidrogenasa eritrocítica / Current status of erythrocytic glucose-6-phosphate dehydrogenase deficiency

La clonación y secuenciamiento del gen de la G6PD abrió un nuevo capítulo en la caracterización de las numerosas variantes enzimáticas de la G6PD. Muchos tipos que se creían diferentes en base a su cinética son en realidad las mismas y se ha encontrado heterogeneidad en algunas que se creían muy homogéneas. Se discute con cierto detalle las variantes A+, A- y mediterránea que tienen una distribución mundial muy alta y sobre las que hay bastante información reciente.