The Experts below are selected from a list of 75 Experts worldwide ranked by ideXlab platform
Ronald Jaffe - One of the best experts on this subject based on the ideXlab platform.
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gastrointestinal neuromuscular pathology in Alpers Disease
The American Journal of Surgical Pathology, 2011Co-Authors: Raj P Kapur, Corinne L Fligner, Bita Maghsoodi, Ronald JaffeAbstract:Alpers Disease is a recessive mitochondrial disorder caused by mutations in POLG1 and characterized primarily by progressive neurological and hepatic degeneration. Intestinal dysmotility is a frequent symptom, but it is often overshadowed by other clinical manifestations. The onset and progression o
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gastrointestinal neuromuscular pathology in Alpers Disease
The American Journal of Surgical Pathology, 2011Co-Authors: Raj P Kapur, Corinne L Fligner, Bita Maghsoodi, Ronald JaffeAbstract:Alpers Disease is a recessive mitochondrial disorder caused by mutations in POLG1 and characterized primarily by progressive neurological and hepatic degeneration. Intestinal dysmotility is a frequent symptom, but it is often overshadowed by other clinical manifestations. The onset and progression of Alpers Disease vary; however, most patients die during childhood, often before a specific diagnosis has been established. The gastrointestinal neuromuscular pathology of 4 patients, obtained largely from postmortem specimens, showed distinctive eosinophilic cytoplasmic granules in a subset of enteric ganglia and patchy atrophy of small intestinal muscularis externa. The cytoplasmic inclusions corresponded to abnormal mitochondria, which have been reported previously in another mitochondrial disorder (mitochondrial neurogastrointestinal encephalomyopathy) but not in Alpers Disease. Recognition of these distinctive light microscopic findings, in an appropriate clinical setting, should prompt the evaluation of an underlying primary mitochondriopathy.
Raj P Kapur - One of the best experts on this subject based on the ideXlab platform.
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gastrointestinal neuromuscular pathology in Alpers Disease
The American Journal of Surgical Pathology, 2011Co-Authors: Raj P Kapur, Corinne L Fligner, Bita Maghsoodi, Ronald JaffeAbstract:Alpers Disease is a recessive mitochondrial disorder caused by mutations in POLG1 and characterized primarily by progressive neurological and hepatic degeneration. Intestinal dysmotility is a frequent symptom, but it is often overshadowed by other clinical manifestations. The onset and progression o
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gastrointestinal neuromuscular pathology in Alpers Disease
The American Journal of Surgical Pathology, 2011Co-Authors: Raj P Kapur, Corinne L Fligner, Bita Maghsoodi, Ronald JaffeAbstract:Alpers Disease is a recessive mitochondrial disorder caused by mutations in POLG1 and characterized primarily by progressive neurological and hepatic degeneration. Intestinal dysmotility is a frequent symptom, but it is often overshadowed by other clinical manifestations. The onset and progression of Alpers Disease vary; however, most patients die during childhood, often before a specific diagnosis has been established. The gastrointestinal neuromuscular pathology of 4 patients, obtained largely from postmortem specimens, showed distinctive eosinophilic cytoplasmic granules in a subset of enteric ganglia and patchy atrophy of small intestinal muscularis externa. The cytoplasmic inclusions corresponded to abnormal mitochondria, which have been reported previously in another mitochondrial disorder (mitochondrial neurogastrointestinal encephalomyopathy) but not in Alpers Disease. Recognition of these distinctive light microscopic findings, in an appropriate clinical setting, should prompt the evaluation of an underlying primary mitochondriopathy.
Bita Maghsoodi - One of the best experts on this subject based on the ideXlab platform.
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gastrointestinal neuromuscular pathology in Alpers Disease
The American Journal of Surgical Pathology, 2011Co-Authors: Raj P Kapur, Corinne L Fligner, Bita Maghsoodi, Ronald JaffeAbstract:Alpers Disease is a recessive mitochondrial disorder caused by mutations in POLG1 and characterized primarily by progressive neurological and hepatic degeneration. Intestinal dysmotility is a frequent symptom, but it is often overshadowed by other clinical manifestations. The onset and progression o
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gastrointestinal neuromuscular pathology in Alpers Disease
The American Journal of Surgical Pathology, 2011Co-Authors: Raj P Kapur, Corinne L Fligner, Bita Maghsoodi, Ronald JaffeAbstract:Alpers Disease is a recessive mitochondrial disorder caused by mutations in POLG1 and characterized primarily by progressive neurological and hepatic degeneration. Intestinal dysmotility is a frequent symptom, but it is often overshadowed by other clinical manifestations. The onset and progression of Alpers Disease vary; however, most patients die during childhood, often before a specific diagnosis has been established. The gastrointestinal neuromuscular pathology of 4 patients, obtained largely from postmortem specimens, showed distinctive eosinophilic cytoplasmic granules in a subset of enteric ganglia and patchy atrophy of small intestinal muscularis externa. The cytoplasmic inclusions corresponded to abnormal mitochondria, which have been reported previously in another mitochondrial disorder (mitochondrial neurogastrointestinal encephalomyopathy) but not in Alpers Disease. Recognition of these distinctive light microscopic findings, in an appropriate clinical setting, should prompt the evaluation of an underlying primary mitochondriopathy.
Corinne L Fligner - One of the best experts on this subject based on the ideXlab platform.
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gastrointestinal neuromuscular pathology in Alpers Disease
The American Journal of Surgical Pathology, 2011Co-Authors: Raj P Kapur, Corinne L Fligner, Bita Maghsoodi, Ronald JaffeAbstract:Alpers Disease is a recessive mitochondrial disorder caused by mutations in POLG1 and characterized primarily by progressive neurological and hepatic degeneration. Intestinal dysmotility is a frequent symptom, but it is often overshadowed by other clinical manifestations. The onset and progression o
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gastrointestinal neuromuscular pathology in Alpers Disease
The American Journal of Surgical Pathology, 2011Co-Authors: Raj P Kapur, Corinne L Fligner, Bita Maghsoodi, Ronald JaffeAbstract:Alpers Disease is a recessive mitochondrial disorder caused by mutations in POLG1 and characterized primarily by progressive neurological and hepatic degeneration. Intestinal dysmotility is a frequent symptom, but it is often overshadowed by other clinical manifestations. The onset and progression of Alpers Disease vary; however, most patients die during childhood, often before a specific diagnosis has been established. The gastrointestinal neuromuscular pathology of 4 patients, obtained largely from postmortem specimens, showed distinctive eosinophilic cytoplasmic granules in a subset of enteric ganglia and patchy atrophy of small intestinal muscularis externa. The cytoplasmic inclusions corresponded to abnormal mitochondria, which have been reported previously in another mitochondrial disorder (mitochondrial neurogastrointestinal encephalomyopathy) but not in Alpers Disease. Recognition of these distinctive light microscopic findings, in an appropriate clinical setting, should prompt the evaluation of an underlying primary mitochondriopathy.
Anu Suomalainen - One of the best experts on this subject based on the ideXlab platform.
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clustering of Alpers Disease mutations and catalytic defects in biochemical variants reveal new features of molecular mechanism of the human mitochondrial replicase pol γ
Nucleic Acids Research, 2011Co-Authors: Liliya Euro, Anu Suomalainen, Gregory A Farnum, Eino Palin, Laurie S KaguniAbstract:Mutations in Pol γ represent a major cause of human mitochondrial Diseases, especially those affecting the nervous system in adults and in children. Recessive mutations in Pol γ represent nearly half of those reported to date, and they are nearly uniformly distributed along the length of the POLG1 gene (Human DNA Polymerase gamma Mutation Database); the majority of them are linked to the most severe form of POLG syndrome, Alpers-Huttenlocher syndrome. In this report, we assess the structure-function relationships for recessive Disease mutations by reviewing existing biochemical data on site-directed mutagenesis of the human, Drosophila and yeast Pol γs, and their homologs from the family A DNA polymerase group. We do so in the context of a molecular model of Pol γ in complex with primer-template DNA, which we have developed based upon the recently solved crystal structure of the apoenzyme form. We present evidence that recessive mutations cluster within five distinct functional modules in the catalytic core of Pol γ. Our results suggest that cluster prediction can be used as a diagnosis-supporting tool to evaluate the pathogenic role of new Pol γ variants.
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abundance of the polg Disease mutations in europe australia new zealand and the united states explained by single ancient european founders
European Journal of Human Genetics, 2007Co-Authors: Anna H Hakonen, David R. Thorburn, Guido Davidzon, Salvatore Dimauro, Renato Salemi, Laurence A Bindoff, Gert Van Goethem, Anu SuomalainenAbstract:We reported previously that the DNA polymerase gamma (POLG) W748S mutation, a common cause of mitochondrial recessive ataxia syndrome (MIRAS), has a common ancient founder for all the Disease chromosomes in Finland, Norway, United Kingdom, and Belgium. Here, we present results showing that the same ancestral chromosome underlies MIRAS and Alpers syndrome in Australia and New Zealand. Furthermore, we show that a second common POLG mutation, A467T, also shows common European ancestry: patients from Australia, New Zealand, and the United States share a common haplotype with the previously reported European patients. These data of ancestral haplotypes indicate that the POLG locus is quite stable and that the recessive W748S and A467T mutations, and probably also G848S, have occurred once in history. They have effectively spread to populations of European descent with carrier frequencies up to 1% in several populations. Our data predict that these mutations are common causes of ataxia and Alpers Disease in the Western world.