共查询到20条相似文献,搜索用时 15 毫秒
1.
van Bruggen R Bautista JM Petropoulou T de Boer M van Zwieten R Gómez-Gallego F Belohradsky BH Hartwig NG Stevens D Mason PJ Roos D 《Blood》2002,100(3):1026-1030
In this study the blood cells of 4 male patients from 2 unrelated families with chronic nonspherocytic anemia and recurrent bacterial infections were investigated. The activity of glucose-6- phosphate dehydrogenase (G6PD) in the red blood cells and in the granulocytes of these patients was below detection level. Moreover, their granulocytes displayed a decreased respiratory burst upon activation. Sequencing of genomic DNA revealed a novel 3-base pair (TCT) deletion in the G6PD gene, predicting the deletion of a leucine at position 61. The mutant G6PD protein was undetectable by Western blotting in the red blood cells and granulocytes of these patients. In phytohemagglutinin-stimulated lymphocytes the G6PD protein was present, but the amount of G6PD protein was strongly diminished in the patients' cells. Purified mutant protein from an Escherichia coli expression system showed decreased heat stability and decreased specific activity. Furthermore, we found that the messenger RNA of G6PD(180-182delTCT) is unstable, which may contribute to the severe G6PD deficiency observed in these patients. We propose the name "G6PD Amsterdam" for this new variant. 相似文献
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Glucose-6-phosphate dehydrogenase aveiro: a de novo mutation associated with chronic nonspherocytic hemolytic anemia 总被引:1,自引:0,他引:1
Costa E Cabeda JM Vieira E Pinto R Pereira SA Ferraz L Santos R Barbot J 《Blood》2000,95(4):1499-1501
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked enzyme abnormality. The clinical phenotype is variable but often predictable from the molecular lesion. Class I variants (the most severe forms of the disease) cluster within exon 10, in a region that, at the protein level, is believed to be involved in dimerization. Here we describe a de novo mutation (C269Y) of a new class I variant (G6PD Aveiro) that maps to exon 8. Mutant and normal alleles were found in both hematopoietic and buccal cells, indicating the presence of mosaicism. The available model of the protein predicts that this lesion lies in proximity to the dimer interface of the molecule. A possible mechanism to explain the severity of the defect is proposed. (Blood. 2000;95:1499-1501) 相似文献
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G6PD San Francisco: a new variant of glucose-6-phosphate dehydrogenase associated with congenital nonspherocytic hemolytic anemia 总被引:2,自引:0,他引:2
Congenital nonspherocytic hemolytic anemia in an adult male of Scandinavian ancestry was associated with virtual absence of G6PD activity in red cells. Characterization of G6PD purified from leukocytes using standard WHO techniques revealed diminished electrophoretic mobility, marked lability on heating at 46 degrees C, normal pH optimum and utilization of alternate substrates (2-deoxy G6P, D-amino NADP), elevated Km NADP, and striking susceptibility to NADPH inhibition. The variant G6PD, which appears to be unique, has been designated G6PD San Francisco. An unusual feature of the variant enzyme, susceptibility to inactivation by brief periods of dialysis, could be prevented by addition of 200 microM NADP to the dialysis solution. In red cells, where G6PD activity was essentially absent, regeneration of reduced glutathione was totally curtailed in vitro, while in leukocytes, where residual G6PD activity was approximately 60% of normal, hexose monophosphate shunt activity, oxygen consumption during phagocytosis, and bacterial killing were unimpaired. Thus, instability of the variant enzyme rather than its unfavorable kinetics appeared to be an important determinant of abnormal cell function. 相似文献
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Molecular abnormality of phosphoglycerate kinase-Uppsala associated with chronic nonspherocytic hemolytic anemia. 总被引:4,自引:3,他引:4 下载免费PDF全文
H Fujii A Yoshida 《Proceedings of the National Academy of Sciences of the United States of America》1980,77(9):5461-5465
Inherited deficiency of phosphoglycerate kinase (PGK; ATP:3-phosphoglycerate 1-phosphotransferase, EC 2.7.2.3) is associated with chronic nonspherocytic hemolytic anemia and mental disorders in man. One such variant, PGK-Uppsala, was purified to homogeneity. PGK-Uppsala had a lower-than-normal specific activity (30% of normal in the backward reaction and about 20% of normal in the forward reaction) and higher-than-normal Michaelis constants for ATP, ADP, 3-phosphoglycerate and 1,3-diphosphoglycerate. Peptide mapping analysis revealed that the structural abnormality of PGK-Uppsala is a single amino acid substitution from arginine to proline at the 206th position. Based on the known complete amino acid sequence of the normal human PGK and the three-dimensional model deduced from horse PGK, correlations between the structural and functional abnormalities of PGK-Uppsala are discussed. Structural abnormalities of PGK-II, which is an electrophoretic variant not associated with enzyme deficiency, and PGK-München, which is associated with enzyme deficiency and heat instability but not associated with hemolytic anemia, are also discussed. 相似文献
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G R Honig E Habacon L N Vida F Matsumoto E Beutler 《American journal of hematology》1979,6(4):353-360
Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency was identified in three children who were evaluated because of chronic nonspherocytic hemolytic anemia. One child is of German extraction, another Puerto Rican, and the third Mexican. In each of the patients the hemolytic process was well compensated, but each had one or more episodes of anemia following exposure to an oxidant drug or with infections. The electrophoretic, functional, and kinetic properties of the mutant enzymes, derived both from the patients' erythrocytes and from cultured fibroblasts, allowed each to be distinguished from G-6-PD variants previously described. 相似文献
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The enzymatic properties of a new glucose-6-phosphate dehydrogenase (G-6-PD) variant (G-6-PD Long Prairie) were studied in a white patient with chronic nonspherocytic hemolysis. The red cells were found to have 2.3%-7.7% normal enzymatic activity. The mutant enzyme exhibited marked heat instability, an increased pH optimum, a moderately decreased Km for G-6-P, and increased utilization of 2-deoxyglucose-6-phosphate and deamino NADP. The Km for NADP and Ki for NADPH were both normal. G-6-PD Long Prairie is an interesting new G-6-PD variant that demonstrates that chronic hemolysis can be associated with modestly decreased G-6-PD activity despite normal sensitivity to inhibition by NADPH. Although increased sensitivity to inhibition by NADPH has been postulated to decrease intracellular enzyme activity, resulting in enhanced susceptibility to hemolysis in certain G-6-PD variants with only moderately decreased enzymatic activity, an alternative mechanism of hemolysis, possibly enzyme thermolability, exists in G-6-PD Long Prairie. 相似文献
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Agudelo-Flórez P Costa-Carvalho BT López JA Redher J Newburger PE Olalla-Saad ST Condino-Neto A 《American journal of hematology》2004,75(3):151-156
Patients with severe leukocyte G6PD deficiency may present with impairment of NADPH oxidase activity and a history of recurrent infections, mimicking the phenotype of chronic granulomatous disease. We report herein a child with recurrent infections who initially received the diagnosis of G6PD deficiency. His erythrocyte G6PD activity was reduced: 1.8 U/g Hb (normal: 12.1 +/- 2.1 U/g Hb). Further studies revealed that G6PD activity in neutrophils, mononuclear leukocytes, and Epstein-Barr virus-transformed B-lymphocytes from the proband was similar to healthy controls. Molecular studies showed that the G6PD deficiency was due a 202 G-->A mutation, the A- variant common in African ethnic groups. The proband also exhibited severely impaired respiratory burst activity, as observed in X-linked CGD. Sequence analysis of genomic DNA showed a 264 G-->A substitution at the 3' splice junction of gp91-phox exon 3. The cDNA sequence showed a deletion of gp91-phox exon 3, giving rise to an unstable or nonfunctional mutant gp91-phox and to the phenotype of X-linked CGD. We propose that clinicians treating a patient with G6PD deficiency during a severe infection episode consider the possibility of temporary or permanent impairment of the phagocytes' microbicidal activity and the eventual association of G6PD deficiency and chronic granulomatous disease. 相似文献
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Shiro Miwa Junichiro Ono Koji Nakashima Shigenobu Abe Takeshi Kageoka Kenji Shinohara Junichi Isobe Hisomu Yamaguchi 《American journal of hematology》1976,1(4):433-442
Two new variants of glucose 6-phosphate dehydrogenase (G6PD) deficiency associated with chronic nonspherocytic hemolytic anemia were discovered in Japan. Gd(-) Tokushima was found in a 17-year-old male whose erythrocytes contained 4.4% of normal enzyme activity. Partially purified enzyme revealed a main band of normal electrophoretic mobility with additional two minor bands of different mobility; normal Km G6P, and Km NADP five- to sixfold higher than normal; normal utilization of 2-deoxy-G6P, galactose-6P, and deamino-NADP; marked thermal instability; a normal pH curve; and normal Ki NADPH. The hemolytic anemia was moderate to severe. Gd(-) Tokyo was characterized from a 15-year-old male who had chronic nonspherocytic hemolytic anemia of mild degree. The erythrocytes contained 3% of normal enzyme activity, and partially purified enzyme revealed slow electrophoretic mobility (90% of normal for both a tris-hydrochloride buffer system and a tris-EDTA-borate buffer system, and 70% of normal for a phosphate buffer system); normal Km G6P and Km NADP; normal utilization of 2-deoxy-G6P, galactose-6P, and deamino-NADP; greatly increased thermal instability; a normal pH curve; and normal Ki NADPH. These two variants are clearly different from hitherto described G6PD variants, including the Japanese variants Gd(-) Heian and Gd(-) Kyoto. The mothers of both Gd(-) Tokushima and Gd(-) Tokyo were found to be heterozygote by an ascorbate-cyanide test. 相似文献
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Tanphaichitr VS Hirono A Pung-amritt P Treesucon A Wanachiwanawin W 《Annals of hematology》2011,90(7):769-775
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common hereditary enzymopathies worldwide. Mostly G6PD
deficient cases are asymptomatic though they may have the risk of neonatal jaundice (NNJ) and acute intravascular hemolysis
during oxidative stress. Chronic nonspherocytic hemolytic anemia (CNSHA) due to G6PD deficiency is rare. In Thailand, one
case was reported 40 years ago and by biochemical study this G6PD was reported to be a new variant G6PD Bangkok. We, herein,
report two families with CNSHA due to G6PD deficiency. In the first family, we have been following up the clinical course
of the patient with G6PD Bangkok. In addition to chronic hemolysis, he had three acute hemolytic episodes requiring blood
transfusions during childhood period. Multiple gallstones were detected at the age of 27. His two daughters who inherited
G6PD Bangkok from him and G6PD Vanua Lava from his wife are asymptomatic. Both of them had NNJ and persistent evidences of
compensated hemolysis. Molecular analysis revealed a novel missense mutation 825 G→C predicting 275 Lys→Asn causing G6PD Bangkok.
In the second family, two male siblings are affected. They had NNJ and several hemolytic episodes which required blood transfusions.
On follow-up they have been diagnosed with chronic hemolysis as evidenced by reticulocytosis and indirect hyperbilirubinemia.
Molecular analysis revealed combined missense mutations in exons 12 and 13. The first mutation was 1376 G→T predicting 459
Arg→Leu (known as G6PD Canton) and the second one was 1502 T→G predicting 501 Phe→Cys. We designated the resulting novel G6PD
variant, G6PD Bangkok Noi. 相似文献
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Akira Hirono Shiro Nakayama Hisaichi Fujii Shiro Miwa 《American journal of hematology》1994,45(2):185-186
Systematic molecular analysis of a Japanese class 1 glucose-6-phosphate dehydrogenase (GGPD) variant (G6PD Kobe) cONA revealed a unique nucleotide substitution (1318 C to T) in exon 11, which predicts a substitution of leucine for phenylalanine at residue 440. This substitution is located in a region surrounding the putative structural NADP-binding domain. The markedly abnormal kinetics of glucose-6-phosphate (GGP) of GGPD Kobe suggest the interaction between both NADP and G6P binding sites. © 1994 Wiley-Liss, Inc. 相似文献
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R D Walter 《Tropenmedizin und Parasitologie》1979,30(1):3-8
Glucose-6-phosphate dehydrogenase specific for NADP (EC 1.1.1.49) was purified to homogeneity from Leishmania tropica promastigotes. The enzyme was found to exist as dimer. The molecular weight of the native enzyme was determined to be 110 000, that of the subunit to be 55 000. The occurence of isoenzymes was demonstrated by isoelectrofocusing. Isoelectric points of glucose-6-phosphate dehydrogenase activity were found at pH 5.5 and pH 6.8. The isoenzymes do not differ with respect to Michaelis constants. The Km-values for NADP and glucose-6-phosphate were determined to be 0.012 mM and 0.15 mM respectively. Glucose-6-phosphate dehydrogenase activity was found to be regulated by product inhibition. The inhibition constant for NADPH was calculated to be 0.05 mM. 相似文献
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Akira Kaneko George Taleo Morris Kalkoa James Yaviong Paul A Reeve Mary Ganczakowski Chihiro Shirakawa Kevin Palmer Takatoshi Kobayakawa Anders Björkman 《Acta tropica》1998,70(3):226-302
Vanuatu is located at the southeast margin of the malarious band extending from southeast Asia to eastern Melanesia. We analysed the malaria situation on different islands of Vanuatu, using passive case detection and malariometric survey data from 1985 to 1992, i.e. after the DDT residual programme ceased and before the impregnated bed-nets programme started on a larger scale. Malaria was mainly hypo-mesoendemic but with hyperendemic spots in certain years and on some islands. The transmission was generally more intense in the northern islands than in the south. In the late 1980s, annual parasite incidence per one thousand population (API) was around 180. The overall parasite rate was 11.9% with Plasmodium falciparum, P. vivax and P. malariae rate of 5.2, 6.7, and 0.1%, respectively. There was a seasonal fluctuation of P. falciparum incidence, whereas the P. vivax incidence was rather stable. Vivax malaria was confined to children less than 10 years old, while the prevalence of P. falciparum only changed moderately with age. The mean rate of glucose 6-phosphate dehydrogenase (G6PD) deficiency among male subjects was in 7.4% but with a wide variation of 0–14.3% on different islands. A positive rank-order correlation was found between malaria incidence and G6PD deficiency rate on the different islands. A reasonable hypothesis is that malaria was introduced to the islands with the first human settlement 4000 years ago, with a geographical malaria distribution similar to the present situation. Different malaria endemicities possibly then selected different prevalences of G6PD deficiency over many generations. 相似文献
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Lactose absorption in patients with glucose 6-phosphate dehydrogenase deficiency with and without favism. 总被引:1,自引:0,他引:1 下载免费PDF全文
BACKGROUND: It has recently been suggested that primary lactase deficiency might have been selected for by malaria, as has been previously shown to occur for thalasaemia and glucose 6-phosphate dehydrogenase (G6PD) deficiency. AIMS: To test this hypothesis, the prevalence of primary lactase deficiency in G6PD deficient subjects and in controls from the area of Sassari (Northern Sardinia) was determined, which in the past was characterised by an intermediate malarial endemicity. SUBJECTS: 70 adult subjects with G6PD deficiency, 34 of whom had a past history of favism, and 50 age matched control subjects. METHODS: The capacity to absorb lactose was assessed by measuring breath hydrogen production after oral administration of lactose (50 g) by a gas chromatographic method. RESULTS: Twenty per cent of G6PD deficient subjects with a positive history of favism and 22% of G6PD deficient subjects without a positive history of favism were lactose absorbers compared with 14% lactose absorbers in the control group. The differences were not statistically significant. CONCLUSIONS: These data show that the prevalence of primary lactase deficiency in the area of Sassari is relatively high, but comparable to that seen in the adult population from another area of southern Italy (Naples) where malaria was less endemic. 相似文献
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