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9 results on '"Wolfram S"'

2. 16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy

Author

Reinthaler, Eva M., Lal, Dennis, Lebon, Sebastien, Hildebrand, Michael S., Dahl, Hans-Henrik M., Regan, Brigid M., Feucht, Martha, Steinböck, Hannelore, Neophytou, Birgit, Ronen, Gabriel M., Roche, Laurian, Gruber-Sedlmayr, Ursula, Geldner, Julia, Haberlandt, Edda, Hoffmann, Per, Herms, Stefan, Gieger, Christian, Waldenberger, Melanie, Franke, Andre, Wittig, Michael, Schoch, Susanne, Becker, Albert J., Hahn, Andreas, Männik, Katrin, Toliat, Mohammad R., Winterer, Georg, Lerche, Holger, Nürnberg, Peter, Mefford, Heather, Scheffer, Ingrid E., Berkovic, Samuel F., Beckmann, Jacques S., Sander, Thomas, Jacquemont, Sebastien, Reymond, Alexandre, Zimprich, Fritz, Neubauer, Bernd A., Reinthaler, Eva M., Zimprich, Fritz, Feucht, Martha, Steinböck, Hannelore, Neophytou, Birgit, Geldner, Julia, Gruber-Sedlmayr, Ursula, Haberlandt, Edda, Ronen, Gabriel M., Roche, Laurian, Lal, Dennis, Nürnberg, Peter, Sander, Thomas, Lerche, Holger, Neubauer, Bernd, Zimprich, Fritz, Mörzinger, Martina, Feucht, Martha, Suls, Arvid, Weckhuysen, Sarah, Claes, Lieve, Deprez, Liesbet, Smets, Katrien, Van Dyck, Tine, Deconinck, Tine, De Jonghe, Peter, Møller, Rikke S, Klitten, Laura L., Hjalgrim, Helle, Møller, Rikke S, Campus, Kiel, Helbig, Ingo, Muhle, Hiltrud, Ostertag, Philipp, von Spiczak, Sarah, Stephani, Ulrich, Nürnberg, Peter, Sander, Thomas, Trucks, Holger, Elger, Christian E., Kleefu-Lie, Ailing A., Kunz, Wolfram S., Surges, Rainer, Gaus, Verena, Janz, Dieter, Sander, Thomas, Schmitz, Bettina, Rosenow, Felix, Klein, Karl Martin, Reif, Philipp S., Oertel, Wolfgang H., Hamer, Hajo M., Becker, Felicitas, Weber, Yvonne, Lerche, Holger, Koeleman, Bobby P.C., de Kovel, Carolien, Lindhout, Dick, Lindhout, Dick, Ameil, Agnès, Andrieux, Joris, Bouquillon, Sonia, Boute, Odile, de Flandre, Jeanne, Cuisset, Jean Marie, Cuvellier, Jean-Christophe, Salengro, Roger, David, Albert, de Vries, Bert, Delrue, Marie-Ange, Doco-Fenzy, Martine, Fernandez, Bridget A., Heron, Delphine, Keren, Boris, Lebel, Robert, Leheup, Bruno, Lewis, Suzanne, Mencarelli, Maria Antonietta, Mignot, Cyril, Minet, Jean-Claude, Moerman, Alexandre, Morice-Picard, Fanny, Mucciolo, Mafalda, Ounap, Katrin, Pasquier, Laurent, Petit, Florence, Ragona, Francesca, Rajcan-Separovic, Evica, Renieri, Alessandra, Rieubland, Claudine, Sanlaville, Damien, Sarrazin, Elisabeth, Shen, Yiping, van Haelst, Mieke, and Silfhout, Anneke Vulto-van

Published
2014
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3. Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32

Author

Steffens, Michael, Leu, Costin, Ruppert, Ann-Kathrin, Zara, Federico, Striano, Pasquale, Robbiano, Angela, Capovilla, Giuseppe, Tinuper, Paolo, Gambardella, Antonio, Bianchi, Amedeo, La Neve, Angela, Crichiutti, Giovanni, de Kovel, Carolien G.F., Kasteleijn-Nolst Trenité, Dorothée, de Haan, Gerrit-Jan, Lindhout, Dick, Gaus, Verena, Schmitz, Bettina, Janz, Dieter, Weber, Yvonne G., Becker, Felicitas, Lerche, Holger, Steinhoff, Bernhard J., Kleefu-Lie, Ailing A., Kunz, Wolfram S., Surges, Rainer, Elger, Christian E., Muhle, Hiltrud, von Spiczak, Sarah, Ostertag, Philipp, Helbig, Ingo, Stephani, Ulrich, Møller, Rikke S., Hjalgrim, Helle, Dibbens, Leanne M., Bellows, Susannah, Oliver, Karen, Mullen, Saul, Scheffer, Ingrid E., Berkovic, Samuel F., Everett, Kate V., Gardiner, Mark R., Marini, Carla, Guerrini, Renzo, Lehesjoki, Anna-Elina, Siren, Auli, Guipponi, Michel, Malafosse, Alain, Thomas, Pierre, Nabbout, Rima, Baulac, Stephanie, Leguern, Eric, Guerrero, Rosa, Serratosa, Jose M., Reif, Philipp S., Rosenow, Felix, Mörzinger, Martina, Feucht, Martha, Zimprich, Fritz, Kapser, Claudia, Schankin, Christoph J., Suls, Arvid, Smets, Katrin, De Jonghe, Peter, Jordanova, Albena, Caglayan, Hande, Yapici, Zuhal, Yalcin, Destina A., Baykan, Betul, Bebek, Nerses, Ozbek, Ugur, Gieger, Christian, Wichmann, Heinz-Erich, Balschun, Tobias, Ellinghaus, David, Franke, Andre, Meesters, Christian, Becker, Tim, Wienker, Thomas F., Hempelmann, Anne, Schulz, Herbert, Rüschendorf, Franz, Leber, Markus, Pauck, Steffen M., Trucks, Holger, Toliat, Mohammad R., Nürnberg, Peter, Avanzini, Giuliano, Koeleman, Bobby P.C., and Sander, Thomas

Published
2012
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6. Linear mtDNA fragments and unusual mtDNA rearrangements associated with pathological deficiency of MGME1 exonuclease

Author

Michal Minczuk, Dominik Cysewski, Cornelia Kornblum, Wolfram S. Kunz, Gábor Zsurka, Susanne Schöler, Andrzej Dziembowski, Aurelio Reyes, Maurizio Moggio, Viktoriya Peeva, Roman J. Szczesny, Thomas J. Nicholls, and M. Sciacco

Subjects
DNA Replication, Exonuclease, Mitochondrial DNA, Mitochondrial Diseases, DNA-Directed DNA Polymerase, DNA, Mitochondrial, Genome, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Genetics, Humans, Molecular Biology, Genetics (clinical), 030304 developmental biology, Gene Rearrangement, mtDNA control region, 0303 health sciences, biology, DNA replication, Articles, General Medicine, Gene rearrangement, DNA Polymerase gamma, Exodeoxyribonucleases, Mutation, biology.protein, Replisome, Homologous recombination, 030217 neurology & neurosurgery
Abstract

MGME1, also known as Ddk1 or C20orf72, is a mitochondrial exonuclease found to be involved in the processing of mitochondrial DNA (mtDNA) during replication. Here, we present detailed insights on the role of MGME1 in mtDNA maintenance. Upon loss of MGME1, elongated 7S DNA species accumulate owing to incomplete processing of 5′ ends. Moreover, an 11-kb linear mtDNA fragment spanning the entire major arc of the mitochondrial genome is generated. In contrast to control cells, where linear mtDNA molecules are detectable only after nuclease S1 treatment, the 11-kb fragment persists in MGME1-deficient cells. In parallel, we observed characteristic mtDNA duplications in the absence of MGME1. The fact that the breakpoints of these mtDNA rearrangements do not correspond to either classical deletions or the ends of the linear 11-kb fragment points to a role of MGME1 in processing mtDNA ends, possibly enabling their repair by homologous recombination. In agreement with its functional involvement in mtDNA maintenance, we show that MGME1 interacts with the mitochondrial replicase PolgA, suggesting that it is a constituent of the mitochondrial replisome, to which it provides an additional exonuclease activity. Thus, our results support the viewpoint that MGME1-mediated mtDNA processing is essential for faithful mitochondrial genome replication and might be required for intramolecular recombination of mtDNA.

Published
2014
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7. On noxious desmin: functional effects of a novel heterozygous desmin insertion mutation on the extrasarcomeric desmin cytoskeleton and mitochondria

Author

Zhigang Xue, Christoph S. Clemen, Thomas Eggermann, Rolf Schröder, Bertrand Goudeau, Jens Reimann, Klaus Zerres, Peter F.M. van der Ven, Sabine Rudnik-Schöneborn, Dieter O. Fürst, Monique Casteras Simon, Zhenlin Li, Wolfram S. Kunz, Patrick Vicart, and Dirk Fischer

Subjects
Adult, Male, Cytoplasm, Heterozygote, DNA, Complementary, Blotting, Western, DNA Mutational Analysis, Molecular Sequence Data, Biology, medicine.disease_cause, Transfection, Polymerase Chain Reaction, Frameshift mutation, Cell Line, Desmin, Muscular Diseases, medicine, Genetics, Humans, Insertion, Amino Acid Sequence, Cytoskeleton, Intermediate filament, Myopathy, Fluorescent Antibody Technique, Indirect, Frameshift Mutation, Microscopy, Immunoelectron, Muscle, Skeletal, Molecular Biology, Genetics (clinical), Genes, Dominant, Mutation, Base Sequence, Adenine, Cardiac muscle, General Medicine, DNA, NAD, Molecular biology, Mitochondria, medicine.anatomical_structure, Mutagenesis, Site-Directed, medicine.symptom
Abstract

Recentstudiesindesmin( / )micehaveshownthatthetargetedablationofdesminleadstopathologicalchangesoftheextrasarcomericintermediatefilamentcytoskeleton,aswellasstructuralandfunctionalabnormalitiesofmitochondriainstriatedmuscle.Here,wereportonanovelheterozygoussingleadenineinsertionmutation(c.5141_5143insA)ina40-year-oldpatientwithadistalmyopathy.Theinsertionmutationleadstoaframeshiftandatruncateddesmin(K239fs242).UsingtransfectionstudiesinSW13andBHK21cells,weshowthattheK239fsX242desminmutantisincapableofformingadesminintermediatefilamentnetwork.Furthermore,itinducesthecollapseofapre-existingdesmincytoskeleton,altersthesubcellulardistributionofmitochondriaandleadstoabnormalcytoplasmicproteinaggregatesreminiscentofdesmin-immunoreactivegranulofilamentousmaterialseenintheultrastructuralanalysisofthepatient’smuscle.Analysisofmitochondrialfunctioninisolatedsaponin-permeablizedskeletalmusclefibresfromourpatientshoweddecreasedmaximalratesofrespirationwiththeNAD-dependentsubstratecombinationglutamateandmalate,aswellasahigheramytalsensitivityofrespiration,indicatinganin vivo inhibitionofcomplexIactivity.OurfindingssuggestthattheheterozygousK239fsX242desmininsertionmutationhasadominantnegativeeffectonthepolymerizationprocessofdesminintermediatefilamentsandaffectsnotonlythesubcellulardistribution,butalsobiochemicalpropertiesofmitochondriaindiseasedhumanskeletalmuscle.Asaconsequence,theintermediatefilamentpathology-inducedmitochondrialdysfunctionmaycontributetothedegeneration/regenerationprocessleadingtoprogressivemuscledysfunctioninhumandesminopathies.INTRODUCTIONMutations of the human desmin gene on chromosome 2q35cause a familial or sporadic form of skeletal myopathyfrequently associated with cardiac abnormalities (OMIM no.125660) (1–7). Desmin, the main intermediate filament (IF)protein in skeletal and cardiac muscle cells, is a structuralcomponent of the extrasarcomeric cytoskeleton which forms athree-dimensional scaffold around myofibrillar Z-discs, therebyinterlinking neighbouring myofibrils and connecting the

Published
2003

8. Metabolic consequences of a novel missense mutation of the mtDNA CO I gene

Author

Rolf Schröder, Wolfram S. Kunz, Armin Heils, Dagmar Kunz, Johannes Rebstock, Karsten Haug, Alexei P. Kudin, Stefan Vielhaber, Dmitry A. Varlamov, Robert Sassen, Christian E. Elger, and Albert J. Becker

Subjects
Mitochondrial DNA, Adolescent, Mutant, DNA Mutational Analysis, Molecular Sequence Data, Drug Resistance, Mutation, Missense, Cytochrome-c Oxidase Deficiency, Epilepsy, Partial, Motor, Mitochondrion, Gene mutation, DNA, Mitochondrial, Oxidative Phosphorylation, Electron Transport Complex IV, Enzyme Stability, Genetics, medicine, Cytochrome c oxidase, Missense mutation, Animals, Humans, Amino Acid Sequence, Muscle, Skeletal, Molecular Biology, Genetics (clinical), Conserved Sequence, biology, Base Sequence, Sequence Homology, Amino Acid, Point mutation, Skeletal muscle, General Medicine, DNA, Molecular biology, Mitochondria, Muscle, medicine.anatomical_structure, Biochemistry, biology.protein, Female
Abstract

We have identified a novel heteroplasmic C6489A missense mutation in the mitochondrial DNA (mtDNA) CO I gene encoding the cytochrome c oxidase (COX) subunit I in a 17-year-old girl with epilepsia partialis continua. This point mutation leads to an exchange of the highly conserved Leu196 to Ileu196. Muscle biopsy showed in single fibers decreased COX activity and lowered binding of COX antibodies, indicating decreased stability of the mutated enzyme. The analysis of blood mtDNA revealed about 30% mutant mtDNA in the patients blood but about 90% mutant mtDNA in the blood of two non-affected family members. Quantitative analysis of the mutation gene dose effect on COX activity on single muscle fiber level revealed a very high threshold-a COX deficiency was observed only in fibers containing95% mutant mtDNA. In apparent contrast to this high mutation gene dose threshold, in vivo investigations of mitochondrial function in saponin-permeabilized muscle fibers of the index patient containing approximately 90% mutated mtDNA showed decreased maximal rates of respiration and an increased sensitivity of fiber respiration to cyanide. This is due to a 2-fold increase of COX flux control on muscle fiber respiration and a 30% decrease of COX metabolic threshold, supporting the concept of tight COX control of oxidative phosphorylation in skeletal muscle.

Published
2002

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