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688 results on '"Sperl, W."'

1. Clinical Experience of Neurological Mitochondrial Diseases in Children and Adults: A Single-Center Study

Author

Rogac M, Neubauer D, Leonardis L, Pecaric N, Meznaric M, Maver A, Sperl W, Garavaglia BM, Lamantea E, and Peterlin B

Subjects
exome-sequencing, magnetic resonance imaging (mri), mitochondrial disease (md), nijmegen mitochondrial disease criteria (mdc), muscle biopsy, Genetics, QH426-470
Abstract

The goal of the study was to retrospectively evaluate a cohort of children and adults with mitochondrial diseases (MDs) in a single-center experience. Neurological clinical examination, brain magnetic resonance imaging (MRI) and spectroscopy, muscle biopsy, metabolic and molecular-genetic analysis were evaluated in 26 children and 36 adult patients with MD in Slovenia from 2004 to 2018. Nijmegen MD criteria (MDC) were applied to all patients and the need for a muscle biopsy was estimated. Exome-sequencing was used in half of the patients. Twenty children (77.0%) and 12 adults (35.0%) scored a total of ≥8 on MDC, a result that is compatible with the diagnosis of definite MD. Yield of exome-sequencing was 7/22 (31.0%), but the method was not applied systematically in all patients from the beginning of diagnostics. Brain MRI morphological changes, which can be an imaging clue for the diagnosis of MD, were found in 17/24 children (71.0%). In 7/26 (29.0%) children, and in 20/30 (67.0%) adults, abnormal mitochondria were found on electron microscopy (EM) and ragged-red fibers were found in 16/30 (53.0%) adults. Respiratory chain enzymes (RCEs) and/or pyruvate dehydrogenase complex (PDHc) activities were abnormal in all the children and six adult cases. First, our data revealed that MDC was useful in the clinical diagnosis of MD, and second, until the use of NGS methods, extensive, laborious and invasive diagnostic procedures were performed to reach a final diagnosis. In patients with suspected MD, there is a need to prioritize molecular diagnosis with the more modern next-generation sequencing (NGS) method.

Published
2022
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7. Pädiatrie

Author

Karall, D., Meisinger, B., Grissenauer, G., Scholl-Bürgi, S., Heinz-Erian, P., Lagler, Florian, Sass, J. O., Grünert, S., Nussbaumer, E.-M., Schwab, K. O., Mönch, E., Hofer, A., Haberlandt, E., Oppl, V., Sperl, W., Spiekerkötter, U., Baumgartner Sigl, S., Stöckler-Ipsiroglu, S., and Ledochowski, Maximilian, editor

Published
2010
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16. Das Deutsche Netzwerk für mitochondriale Erkrankungen (mitoNET)

Author

Büchner, B., Gallenmüller, C., Lautenschläger, R., Kuhn, K., Wittig, I., Schöls, L., Rapaport, D., Seelow, D., Freisinger, P., Prokisch, H., Sperl, W., Wenz, T., Behl, C., Deschauer, M., Kornblum, C., Schneiderat, P., Abicht, A., Schuelke, M., Meitinger, T., Klopstock, T., and und das mitoNET-Consortium

Published
2012
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17. Mutation analysis in 54 propionic acidemia patients

Author

Kraus, J. P., Spector, E., Venezia, S., Estes, P., Chiang, P. W., Creadon-Swindell, G., Müllerleile, S., de Silva, L., Barth, M., Walter, M., Walter, K., Meissner, T., Lindner, M., Ensenauer, R., Santer, R., Bodamer, O. A., Baumgartner, M. R., Brunner-Krainz, M., Karall, D., Haase, C., Knerr, I., Marquardt, T., Hennermann, J. B., Steinfeld, R., Beblo, S., Koch, H. G., Konstantopoulou, V., Scholl-Bürgi, S., van Teeffelen-Heithoff, A., Suormala, T., Ugarte, M., Sperl, W., Superti-Furga, A., Schwab, K. O., Grünert, S. C., and Sass, J. O.

Published
2012
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18. Propionic acidemia: neonatal versus selective metabolic screening

Author

Grünert, S. C., Müllerleile, S., de Silva, L., Barth, M., Walter, M., Walter, K., Meissner, T., Lindner, M., Ensenauer, R., Santer, R., Bodamer, O. A., Baumgartner, M. R., Brunner-Krainz, M., Karall, D., Haase, C., Knerr, I., Marquardt, T., Hennermann, J. B., Steinfeld, R., Beblo, S., Koch, H. G., Konstantopoulou, V., Scholl-Bürgi, S., van Teeffelen-Heithoff, A., Suormala, T., Sperl, W., Kraus, J. P., Superti-Furga, A., Schwab, K. O., and Sass, J. O.

Published
2012
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22. Biallelic C1QBP Mutations Cause Severe Neonatal-, Childhood-, or Later-Onset Cardiomyopathy Associated with Combined Respiratory-Chain Deficiencies

Author

Feichtinger R. G., Olahova M., Kishita Y., Garone C., Kremer L. S., Yagi M., Uchiumi T., Jourdain A. A., Thompson K., D'Souza A. R., Kopajtich R., Alston C. L., Koch J., Sperl W., Mastantuono E., Strom T. M., Wortmann S. B., Meitinger T., Pierre G., Chinnery P. F., Chrzanowska-Lightowlers Z. M., Lightowlers R. N., DiMauro S., Calvo S. E., Mootha V. K., Moggio M., Sciacco M., Comi G. P., Ronchi D., Murayama K., Ohtake A., Rebelo-Guiomar P., Kohda M., Kang D., Mayr J. A., Taylor R. W., Okazaki Y., Minczuk M., Prokisch H., Garone, Caterina [0000-0003-4928-1037], Chinnery, Patrick [0000-0002-7065-6617], Minczuk, Michal [0000-0001-8242-1420], Apollo - University of Cambridge Repository, Feichtinger R.G., Olahova M., Kishita Y., Garone C., Kremer L.S., Yagi M., Uchiumi T., Jourdain A.A., Thompson K., D'Souza A.R., Kopajtich R., Alston C.L., Koch J., Sperl W., Mastantuono E., Strom T.M., Wortmann S.B., Meitinger T., Pierre G., Chinnery P.F., Chrzanowska-Lightowlers Z.M., Lightowlers R.N., DiMauro S., Calvo S.E., Mootha V.K., Moggio M., Sciacco M., Comi G.P., Ronchi D., Murayama K., Ohtake A., Rebelo-Guiomar P., Kohda M., Kang D., Mayr J.A., Taylor R.W., Okazaki Y., Minczuk M., and Prokisch H.

Subjects
Male, Mitochondrial Diseases, Protein Conformation, Sequence Homology, Severity of Illness Index, Cohort Studies, Mice, Mitochondrial Disease, Age of Onset, Cells, Cultured, Allele, multiple mtDNA deletions, Middle Aged, Pedigree, mitochondria, Child, Preschool, Adult, Aged, Alleles, Amino Acid Sequence, Animals, Cardiomyopathies/complications, Cardiomyopathies/genetics, Cardiomyopathies/pathology, Carrier Proteins/chemistry, Carrier Proteins/genetics, Carrier Proteins/metabolism, DNA, Mitochondrial, Electron Transport/physiology, Embryo, Mammalian/metabolism, Embryo, Mammalian/pathology, Female, Fibroblasts/metabolism, Fibroblasts/pathology, Humans, Infant, Newborn, Mitochondrial Diseases/complications, Mitochondrial Diseases/genetics, Mitochondrial Diseases/pathology, Mitochondrial Proteins/chemistry, Mitochondrial Proteins/genetics, Mitochondrial Proteins/metabolism, Mutation, Oxidative Phosphorylation, Young Adult, MAM33, PEO, lactate, myopathy, oxidative phosphorylation, p32, progressive external ophthalmoplegia, multiple mtDNA deletion, Fibroblast, Cardiomyopathies, Human, Article, Electron Transport, Mitochondrial Proteins, Mitochondrial Protein, Cardiomyopathie, Animal, Fibroblasts, Embryo, Mammalian, Cohort Studie, Carrier Protein, Carrier Proteins
Abstract

Complement component 1 Q subcomponent-binding protein (C1QBP; also known as p32) is a multi-compartmental protein whose precise function remains unknown. It is an evolutionary conserved multifunctional protein localized primarily in the mitochondrial matrix and has roles in inflammation and infection processes, mitochondrial ribosome biogenesis, and regulation of apoptosis and nuclear transcription. It has an N-terminal mitochondrial targeting peptide that is proteolytically processed after import into the mitochondrial matrix, where it forms a homotrimeric complex organized in a doughnut-shaped structure. Although C1QBP has been reported to exert pleiotropic effects on many cellular processes, we report here four individuals from unrelated families where biallelic mutations in C1QBP cause a defect in mitochondrial energy metabolism. Infants presented with cardiomyopathy accompanied by multisystemic involvement (liver, kidney, and brain), and children and adults presented with myopathy and progressive external ophthalmoplegia. Multiple mitochondrial respiratory-chain defects, associated with the accumulation of multiple deletions of mitochondrial DNA in the later-onset myopathic cases, were identified in all affected individuals. Steady-state C1QBP levels were decreased in all individuals' samples, leading to combined respiratory-chain enzyme deficiency of complexes I, III, and IV. C1qbp -/- mouse embryonic fibroblasts (MEFs) resembled the human disease phenotype by showing multiple defects in oxidative phosphorylation (OXPHOS). Complementation with wild-type, but not mutagenized, C1qbp restored OXPHOS protein levels and mitochondrial enzyme activities in C1qbp -/- MEFs. C1QBP deficiency represents an important mitochondrial disorder associated with a clinical spectrum ranging from infantile lactic acidosis to childhood (cardio)myopathy and late-onset progressive external ophthalmoplegia.

Published
2017

40. Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Author

Borghini, L, Png, E, Binder, A, Wright, VJ, Pinnock, E, de Groot, R, Hazelzet, J, Emonts, M, Van der Flier, M, Schlapbach, LJ, Anderson, S, Secka, F, Salas, A, Fink, C, Carrol, ED, Pollard, AJ, Coin, LJ, Kuijpers, TW, Martinon-Torres, F, Zenz, W, Levin, M, Hibberd, ML, Davila, S, Gormley, S, Hamilton, S, Herberg, J, Hourmat, B, Hoggart, C, Kaforou, M, Sancho-Shimizu, V, Abdulla, A, Agapow, P, Bartlett, M, Bellos, E, Eleftherohorinou, H, Galassini, R, Inwald, D, Mashbat, M, Menikou, S, Mustafa, S, Nadel, S, Rahman, R, Thakker, C, Bokhandi, S, Power, S, Barham, H, Pathan, N, Ridout, J, White, D, Thurston, S, Faust, S, Patel, S, McCorkell, J, Davies, P, Cratev, L, Navarra, H, Carter, S, Ramaiah, R, Patel, R, Tuffrey, C, Gribbin, A, McCready, S, Peters, M, Hardy, K, Standing, F, O'Neill, L, Abelake, E, Deep, A, Nsirim, E, Willis, L, Young, Z, Royad, C, White, S, Fortune, PM, Hudnott, P, Alvez Gonzalez, F, Barral-Arca, R, Cebey-Lopez, M, Jose Curras-Tuala, M, Garcia, N, Garcia Vicente, L, Gomez-Carballa, A, Gomez Rial, J, Grela Beiroa, A, Justicia Grande, A, Leborans Iglesias, P, Martinez Santos, AE, Martinon-Torres, N, Martinon Sanchez, JM, Mosquera Perez, B, Obando Pacheco, P, Pardo-Seco, J, Pischedda, S, Rivero Calle, I, Rodriguez-Tenreiro, C, Redondo-Collazo, L, Seren Fernandez, S, Porto Silva, MDS, Vega, A, Beatriz Reyes, S, Leon Leon, MC, Navarro Mingorance, A, Gabaldo Barrios, X, Onate Vergara, E, Concha Torre, A, Vivanco, A, Fernandez, R, Gimenez Sanchez, F, Sanchez Forte, M, Rojo, P, Ruiz Contreras, J, Palacios, A, Navarro, M, Alvarez Alvarez, C, Jose Lozano, M, Carreras, E, Brio Sanagustin, S, Neth, O, Martinez Padilla, MDC, Prieto Tato, LM, Guillen, S, Fernandez Silveira, L, Moreno, D, van Furth, AMT, van der Flier, M, Boeddha, NP, Driessen, GJA, Pajkrt, D, Sanders, EAM, van de Beek, D, van der Ende, A, Philipsen, HLA, Adeel, AOA, Breukels, MA, Brinkman, DMC, de Korte, CCMM, de Vries, E, de Waal, WJ, Dekkers, R, Dings-Lammertink, A, Doedens, RA, Donker, AE, Dousma, M, Faber, TE, Gerrits, GPJM, Gerver, JAM, Heidema, J, Homan-van der Veen, J, Jacobs, MAM, Jansen, NJG, Kawczynski, P, Klucovska, K, Kneyber, MCJ, Koopman-Keemink, Y, Langenhorst, VJ, Leusink, J, Loza, BF, Merth, IT, Miedema, CJ, Neeleman, C, Noordzij, JG, Obihara, CC, van Overbeek-van Gils, ALT, Poortman, GH, Potgieter, ST, Potjewijd, J, Rosias, PPR, Sprong, T, ten Tussher, GW, Thio, BJ, Tramper-Stranders, GA, van Deuren, M, van der Meer, H, van Kuppevelt, AJM, van Wermeskerken, AM, Verwijs, WA, Wolfs, TFW, Agyeman, P, Aebi, C, Berger, C, Giannoni, E, Stocker, M, Posfay-Barbe, KM, Heininger, U, Bernhard-Stirnemann, S, Niederer-Loher, A, Kahlert, C, Hasters, P, Relly, C, Baer, W, Paulus, S, Frederick, H, Jennings, R, Johnston, J, Kenwright, R, Agbeko, R, Bojang, K, Sarr, I, Kebbeh, N, Sey, G, Saidykhan, M, Cole, F, Thomas, G, Antonio, M, Walcher, W, Geishofer, G, Klobassa, D, Martin, M, Pfurtscheller, K, Reiter, K, Roedl, S, Zobel, G, Zoehrer, B, Toepke, B, Fucik, P, Gabriel, M, Penzien, JM, Diab, G, Miething, R, Deeg, KH, Hammer, J, Varnholt, V, Schmidt, A, Bindl, L, Sillaber, U, Huemer, C, Meier, P, Simic-Schleicher, G, Markart, M, Pfau, E, Broede, H, Ausserer, B, Kalhoff, H, Arpe, V, Schweitzer-Krantz, S, Kasper, J-M, Loranth, K, Bittrich, HJ, Simma, B, Klinge, J, Fedlmaier, M, Weigand, N, Herting, E, Grube, R, Fusch, C, Gruber, A, Schimmel, U, Knaufer-Schiefer, S, Laessig, W, Hennenberger, A, von der Wense, A, Tillmann, R, Schwarick, J, Sitzmann, FC, Streif, W, Mueller, H, Kurnik, P, Groneck, P, Weiss, U, Groeblacher-Roth, H, Bensch, J, Moser, R, Schwarz, R, Lenz, K, Hofmann, T, Goepel, W, Schulz, D, Berger, T, Hauser, E, Foerster, KM, Peters, J, Nicolai, TH, Kumlien, B, Beckmann, R, Seitz, C, Hueseman, D, Schuermann, R, Ta, VH, Weikmann, E, Evert, W, Hautz, J, Seidenberg, J, Wocko, L, Luigs, P, Reiter, H-L, Quietzach, J, Koenig, M, Herrmann, J, Mitter, H, Seidler, E, Maak, B, Sperl, W, Zwiauer, K, Meissl, M, Koch, R, Cremer, M, Breuer, HA, Goerke, W, Nossal, R, Pernice, W, Brangenberg, R, Salzer, HR, Koch, H, Schaller, G, Paky, F, Strasser, F, Eitelberger, F, Sontheimer, D, Lischka, A, Kronberger, M, Dilch, A, Scheibenpflug, C, Bruckner, R, Mahler, K, Runge, K, Kunze, W, Schermann, P, Borghini, L, Png, E, Binder, A, Wright, VJ, Pinnock, E, de Groot, R, Hazelzet, J, Emonts, M, Van der Flier, M, Schlapbach, LJ, Anderson, S, Secka, F, Salas, A, Fink, C, Carrol, ED, Pollard, AJ, Coin, LJ, Kuijpers, TW, Martinon-Torres, F, Zenz, W, Levin, M, Hibberd, ML, Davila, S, Gormley, S, Hamilton, S, Herberg, J, Hourmat, B, Hoggart, C, Kaforou, M, Sancho-Shimizu, V, Abdulla, A, Agapow, P, Bartlett, M, Bellos, E, Eleftherohorinou, H, Galassini, R, Inwald, D, Mashbat, M, Menikou, S, Mustafa, S, Nadel, S, Rahman, R, Thakker, C, Bokhandi, S, Power, S, Barham, H, Pathan, N, Ridout, J, White, D, Thurston, S, Faust, S, Patel, S, McCorkell, J, Davies, P, Cratev, L, Navarra, H, Carter, S, Ramaiah, R, Patel, R, Tuffrey, C, Gribbin, A, McCready, S, Peters, M, Hardy, K, Standing, F, O'Neill, L, Abelake, E, Deep, A, Nsirim, E, Willis, L, Young, Z, Royad, C, White, S, Fortune, PM, Hudnott, P, Alvez Gonzalez, F, Barral-Arca, R, Cebey-Lopez, M, Jose Curras-Tuala, M, Garcia, N, Garcia Vicente, L, Gomez-Carballa, A, Gomez Rial, J, Grela Beiroa, A, Justicia Grande, A, Leborans Iglesias, P, Martinez Santos, AE, Martinon-Torres, N, Martinon Sanchez, JM, Mosquera Perez, B, Obando Pacheco, P, Pardo-Seco, J, Pischedda, S, Rivero Calle, I, Rodriguez-Tenreiro, C, Redondo-Collazo, L, Seren Fernandez, S, Porto Silva, MDS, Vega, A, Beatriz Reyes, S, Leon Leon, MC, Navarro Mingorance, A, Gabaldo Barrios, X, Onate Vergara, E, Concha Torre, A, Vivanco, A, Fernandez, R, Gimenez Sanchez, F, Sanchez Forte, M, Rojo, P, Ruiz Contreras, J, Palacios, A, Navarro, M, Alvarez Alvarez, C, Jose Lozano, M, Carreras, E, Brio Sanagustin, S, Neth, O, Martinez Padilla, MDC, Prieto Tato, LM, Guillen, S, Fernandez Silveira, L, Moreno, D, van Furth, AMT, van der Flier, M, Boeddha, NP, Driessen, GJA, Pajkrt, D, Sanders, EAM, van de Beek, D, van der Ende, A, Philipsen, HLA, Adeel, AOA, Breukels, MA, Brinkman, DMC, de Korte, CCMM, de Vries, E, de Waal, WJ, Dekkers, R, Dings-Lammertink, A, Doedens, RA, Donker, AE, Dousma, M, Faber, TE, Gerrits, GPJM, Gerver, JAM, Heidema, J, Homan-van der Veen, J, Jacobs, MAM, Jansen, NJG, Kawczynski, P, Klucovska, K, Kneyber, MCJ, Koopman-Keemink, Y, Langenhorst, VJ, Leusink, J, Loza, BF, Merth, IT, Miedema, CJ, Neeleman, C, Noordzij, JG, Obihara, CC, van Overbeek-van Gils, ALT, Poortman, GH, Potgieter, ST, Potjewijd, J, Rosias, PPR, Sprong, T, ten Tussher, GW, Thio, BJ, Tramper-Stranders, GA, van Deuren, M, van der Meer, H, van Kuppevelt, AJM, van Wermeskerken, AM, Verwijs, WA, Wolfs, TFW, Agyeman, P, Aebi, C, Berger, C, Giannoni, E, Stocker, M, Posfay-Barbe, KM, Heininger, U, Bernhard-Stirnemann, S, Niederer-Loher, A, Kahlert, C, Hasters, P, Relly, C, Baer, W, Paulus, S, Frederick, H, Jennings, R, Johnston, J, Kenwright, R, Agbeko, R, Bojang, K, Sarr, I, Kebbeh, N, Sey, G, Saidykhan, M, Cole, F, Thomas, G, Antonio, M, Walcher, W, Geishofer, G, Klobassa, D, Martin, M, Pfurtscheller, K, Reiter, K, Roedl, S, Zobel, G, Zoehrer, B, Toepke, B, Fucik, P, Gabriel, M, Penzien, JM, Diab, G, Miething, R, Deeg, KH, Hammer, J, Varnholt, V, Schmidt, A, Bindl, L, Sillaber, U, Huemer, C, Meier, P, Simic-Schleicher, G, Markart, M, Pfau, E, Broede, H, Ausserer, B, Kalhoff, H, Arpe, V, Schweitzer-Krantz, S, Kasper, J-M, Loranth, K, Bittrich, HJ, Simma, B, Klinge, J, Fedlmaier, M, Weigand, N, Herting, E, Grube, R, Fusch, C, Gruber, A, Schimmel, U, Knaufer-Schiefer, S, Laessig, W, Hennenberger, A, von der Wense, A, Tillmann, R, Schwarick, J, Sitzmann, FC, Streif, W, Mueller, H, Kurnik, P, Groneck, P, Weiss, U, Groeblacher-Roth, H, Bensch, J, Moser, R, Schwarz, R, Lenz, K, Hofmann, T, Goepel, W, Schulz, D, Berger, T, Hauser, E, Foerster, KM, Peters, J, Nicolai, TH, Kumlien, B, Beckmann, R, Seitz, C, Hueseman, D, Schuermann, R, Ta, VH, Weikmann, E, Evert, W, Hautz, J, Seidenberg, J, Wocko, L, Luigs, P, Reiter, H-L, Quietzach, J, Koenig, M, Herrmann, J, Mitter, H, Seidler, E, Maak, B, Sperl, W, Zwiauer, K, Meissl, M, Koch, R, Cremer, M, Breuer, HA, Goerke, W, Nossal, R, Pernice, W, Brangenberg, R, Salzer, HR, Koch, H, Schaller, G, Paky, F, Strasser, F, Eitelberger, F, Sontheimer, D, Lischka, A, Kronberger, M, Dilch, A, Scheibenpflug, C, Bruckner, R, Mahler, K, Runge, K, Kunze, W, and Schermann, P

Abstract

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes.

Published
2019

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