The Experts below are selected from a list of 402 Experts worldwide ranked by ideXlab platform
Hugo W. Moser - One of the best experts on this subject based on the ideXlab platform.
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adrenoleukodystrophy incidence new mutation rate and results of extended family screening
Annals of Neurology, 2001Co-Authors: Lena Bezman, Gerald V Raymond, Paul A Watkins, Kirby D Smith, Nancy E Kass, Piero Rinaldo, Ann B. Moser, Hugo W. MoserAbstract:Utilizing the plasma very long chain fatty acid assay, supplemented by mutation analysis and immunofluorescence assay, we determined the number of X-linked adrenoleukodystrophy (X-ALD) Hemizygotes from the United States identified each year in the two laboratories that perform most of the assays in this country: the Kennedy Krieger Institute between 1981 and 1998 and the Mayo Clinic Rochester from 1996 to 1998. The minimum frequency of Hemizygotes identified in the United States is estimated to be 1:42,000 and that of Hemizygotes plus heterozygotes 1:16,800. Our studies involved 616 pedigrees with a total of 12,787 identified at-risk members. Diagnostic assays were performed in 4,169 at-risk persons (33%) and included members of the extended family. Only 5% of male probands and 1.7% of X-ALD Hemizygotes were found to have new mutations. The extended family testing led to the identification of 594 Hemizygotes and 1,270 heterozygotes. Two hundred fifty of the newly identified Hemizygotes were asymptomatic and represent the group in which therapy has the greatest chance of success. Identification of heterozygotes provides the opportunity for disease prevention through genetic counseling. Diagnostic tests should be offered to all at-risk relatives of X-ALD patients and should include members of the extended family. Ann Neurol 2001;49:512–517
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adrenoleukodystrophy incidence new mutation rate and results of extended family screening
Annals of Neurology, 2001Co-Authors: Lena Bezman, Gerald V Raymond, Paul A Watkins, Kirby D Smith, Nancy E Kass, Piero Rinaldo, Ann B. Moser, Hugo W. MoserAbstract:Utilizing the plasma very long chain fatty acid assay, supplemented by mutation analysis and immunofluorescence assay, we determined the number of X-linked adrenoleukodystrophy (X-ALD) Hemizygotes from the United States identified each year in the two laboratories that perform most of the assays in this country: the Kennedy Krieger Institute between 1981 and 1998 and the Mayo Clinic Rochester from 1996 to 1998. The minimum frequency of Hemizygotes identified in the United States is estimated to be 1:42,000 and that of Hemizygotes plus heterozygotes 1:16,800. Our studies involved 616 pedigrees with a total of 12,787 identified at-risk members. Diagnostic assays were performed in 4,169 at-risk persons (33%) and included members of the extended family. Only 5% of male probands and 1.7% of X-ALD Hemizygotes were found to have new mutations. The extended family testing led to the identification of 594 Hemizygotes and 1,270 heterozygotes. Two hundred fifty of the newly identified Hemizygotes were asymptomatic and represent the group in which therapy has the greatest chance of success. Identification of heterozygotes provides the opportunity for disease prevention through genetic counseling. Diagnostic tests should be offered to all at-risk relatives of X-ALD patients and should include members of the extended family.
Chris Drakeley - One of the best experts on this subject based on the ideXlab platform.
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glucose 6 phosphate dehydrogenase status and risk of hemolysis in plasmodium falciparum infected african children receiving single dose primaquine
Antimicrobial Agents and Chemotherapy, 2014Co-Authors: Alice C Eziefula, Helmi Pett, Lynn Grignard, Salome Opus, Moses Kiggundu, Moses R Kamya, Shunmay Yeung, Sarah G Staedke, Teun Bousema, Chris DrakeleyAbstract:Glucose-6-phosphate dehydrogenase (G6PD) enzyme function and genotype were determined in Ugandan children with uncomplicated falciparum malaria enrolled in a primaquine trial after exclusion of severe G6PD deficiency by fluorescent spot test. G6PD A- heterozygotes and Hemizygotes/homozygotes experienced dose-dependent lower hemoglobin concentrations after treatment. No severe anemia was observed.
M. Beck - One of the best experts on this subject based on the ideXlab platform.
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anderson fabry disease clinical manifestations of disease in female heterozygotes
Journal of Inherited Metabolic Disease, 2001Co-Authors: Catharina Whybra, Chr. Kampmann, I. Willers, K. Brühl, Susanna Bunge, Jorg Kriegsmann, J Davies, M. BeckAbstract:Anderson–Fabry disease is a rare, X-chromosomal lipid storage disorder caused by a deficiency of lysosomal α-galactosidase A. Clinical manifestations of Anderson–Fabry disease include excruciating pain in the extremities (acroparaesthesia), skin vessel ectasia (angiokeratoma), corneal and lenticular opacity, cardiovascular disease, stroke and renal failure, only renal failure being a frequent cause of death. Heterozygote female carriers have often been reported as being asymptomatic or having an attenuated form of the disease. To evaluate the spectrum of clinical signs in heterozygotes, a comprehensive clinical examination was performed on 20 carriers of Anderson–Fabry disease. This revealed that, in addition to the skin manifestation, various other clinical manifestations of the disease are present, including acroparaesthesia, kidney dysfunction, cerebrovascular disease, and gastrointestinal and heart problems. It therefore appears that Anderson–Fabry disease affects both Hemizygotes and heterozyotes and therefore should be considered to be an X-linked dominant disease.
C Ruwende - One of the best experts on this subject based on the ideXlab platform.
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glucose 6 phosphate dehydrogenase deficiency and malaria
Journal of Molecular Medicine, 1998Co-Authors: C Ruwende, Adrian V S HillAbstract:Glucose-6-phosphate dehydrogenase (G6PD) is a cytoplasmic enzyme that is essential for a cell’s capacity to withstand oxidant stress. G6PD deficiency is the commonest enzymopathy of humans, affecting over 400 million persons worldwide. The geographical correlation of its distribution with the historical endemicity of malaria suggests that 66PD deficiency has risen in frequency through natural selection by malaria. This is supported by data from in vitro studies that demonstrate impaired growth of P. falciparum parasites in G6PD-deficient erythrocytes. Attempts to confirm that G6PD deficiency is protective in field studies of malaria have yielded conflicting results, but recent results from large case control studies conducted in East and West Africa provide strong evidence that the most common African G6PD deficiency variant, G6PD A–, is associated with a significant reduction in the risk of severe malaria for both G6PD female heterozygotes and male Hemizygotes. The effect of female homozygotes on severe malaria remains unclear but can probably be assumed to be similar to that of comparably deficient male Hemizygotes.
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natural selection of hemi and heterozygotes for g6pd deficiency in africa by resistance to severe malaria
Nature, 1995Co-Authors: C Ruwende, S C Khoo, Robert W Snow, S N Yates, Dominic P Kwiatkowski, Sunetra Gupta, Peter Warn, Catherine E M AllsoppAbstract:Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymopathy of humans, affects over 400 million people. The geographical correlation of its distribution with the historical endemicity of malaria suggests that this disorder has risen in frequency through natural selection by malaria. However, attempts to confirm that G6PD deficiency is protective in case-control studies of malaria have yielded conflicting results. Hence, for this X-linked disorder, it is unclear whether both male Hemizygotes and female heterozygotes are protected or, as frequently suggested, only females. Furthermore, how much protection may be afforded is unknown. Here we report that, in two large case-control studies of over 2,000 African children, the common African form of G6PD deficiency (G6PD A-) is associated with a 46-58% reduction in risk of severe malaria for both female heterozygotes and male Hemizygotes. A mathematical model incorporating the measured selective advantage against malaria suggests that a counterbalancing selective disadvantage, associated with this enzyme deficiency, has retarded its rise in frequency in malaria-endemic regions. Although G6PD deficiency is now regarded as a generally benign disorder, in earlier environmental conditions it could have been significantly disadvantageous.
Morimi Shimada - One of the best experts on this subject based on the ideXlab platform.
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histochemical study of mitochondrial enzymes in cerebellar cortex of macular mutant mouse a model of menkes kinky hair disease
Acta Neuropathologica, 1994Co-Authors: Masao Kumode, Tsunekazu Yamano, Morimi ShimadaAbstract:The cerebellar Purkinje cells in the Hemizygote of the macular mutant mouse contain numerous abnormal mitochondria which show a marked decrease in cytochrome c oxidase activity. Using histochemical methods we studied the activity of other mitochondrial enzymes, such as NADH diaphorase and succinic dehydrogenase, in the cerebellar cortex of this mutant mouse. Such activities were markedly increased in the Purkinje cells, especially in the soma and stem dendrite, from 10 days after birth in the Hemizygote as compared with findings in normal littermates. These results were considered to be due to an increased number of abnormal mitochondria.