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Your search keyword '"CHINNERY, PATRICK F."' showing total 14 results
Start Over Author "CHINNERY, PATRICK F." Journal human molecular genetics
14 results on '"CHINNERY, PATRICK F."'

4. A novel mechanism causing imbalance of mitochondrial fusion and fission in human myopathies

Author

Bartsakoulia, Marina, Pyle, Angela, Troncoso-Chandía, Diego, Vial-Brizzi, Josefa, Paz-Fiblas, Marysol V, Duff, Jennifer, Griffin, Helen, Boczonadi, Veronika, Lochmüller, Hanns, Kleinle, Stephanie, Chinnery, Patrick F, Grünert, Sarah, Kirschner, Janbernd, Eisner, Verónica, Horvath, Rita, Chinnery, Patrick [0000-0002-7065-6617], Horvath, Rita [0000-0002-9841-170X], and Apollo - University of Cambridge Repository

Subjects
Male, Electron Transport Complex I, Primary Cell Culture, Mutation, Missense, Articles, Fibroblasts, Peptide Elongation Factors, Mitochondrial Dynamics, GTP Phosphohydrolases, Electron Transport Complex IV, Mitochondrial Proteins, Muscular Diseases, Humans, Female
Abstract

Mitochondrial dynamics play an important role in cellular homeostasis and a variety of human diseases are linked to its dysregulated function. Here, we describe a 15-year-old boy with a novel disease caused by altered mitochondrial dynamics. The patient was the second child of consanguineous Jewish parents. He developed progressive muscle weakness and exercise intolerance at 6 years of age. His muscle biopsy revealed mitochondrial myopathy with numerous ragged red and cytochrome c oxidase (COX) negative fibers and combined respiratory chain complex I and IV deficiency. MtDNA copy number was elevated and no deletions of the mtDNA were detected in muscle DNA. Whole exome sequencing identified a homozygous nonsense mutation (p.Q92*) in the MIEF2 gene encoding the mitochondrial dynamics protein of 49 kDa (MID49). Immunoblotting revealed increased levels of proteins promoting mitochondrial fusion (MFN2, OPA1) and decreased levels of the fission protein DRP1. Fibroblasts of the patient showed elongated mitochondria, and significantly higher frequency of fusion events, mtDNA abundance and aberrant mitochondrial cristae ultrastructure, compared with controls. Thus, our data suggest that mutations in MIEF2 result in imbalanced mitochondrial dynamics and a combined respiratory chain enzyme defect in skeletal muscle, leading to mitochondrial myopathy.

Published
2018

6. A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinsonʼs disease

Author

Holmans, Peter, Moskvina, Valentina, Jones, Lesley, Sharma, Manu, Vedernikov, Alexey, Buchel, Finja, Sadd, Mohamad, Bras, Jose M., Bettella, Francesco, Nicolaou, Nayia, Simón-Sánchez, Javier, Mittag, Florian, Gibbs, J. Raphael, Schulte, Claudia, Durr, Alexandra, Guerreiro, Rita, Hernandez, Dena, Brice, Alexis, Stefánsson, Hreinn, Majamaa, Kari, Gasser, Thomas, Heutink, Peter, Wood, Nicholas W., Martinez, Maria, Singleton, Andrew B., Nalls, Michael A., Hardy, John, Morris, Huw R., Williams, Nigel M., Arepalli, Sampath, Barker, Roger, Barrett, Jeffrey, Ben-Shlomo, Yoav, Berendse, Henk W., Berg, Daniela, Bhatia, Kailash, de Bie, Rob M.A., Biffi, Alessandro, Bloem, Bas, Brice, Alexis, Bochdanovits, Zoltan, Bonin, Michael, Bras, Jose M., Brockmann, Kathrin, Brooks, Janet, Burn, David J., Charlesworth, Gavin, Chen, Honglei, Chinnery, Patrick F., Chong, Sean, Clarke, Carl E., Cookson, Mark R., Cooper, Jonathan M., Corvol, Jen-Christophe, Counsell, Carl, Damier, Philippe, Dartigues, Jean Francois, Deloukas, Panagiotis, Deuschl, Günther, Dexter, David T., van Dijk, Karin D., Dillman, Allissa, Durif, Frank, Durr, Alexandra, Edkins, Sarah, Evans, Jonathan R., Foltynie, Thomas, Gao, Jianjun, Gardner, Michelle, Gasser, Thomas, Gibbs, J. Raphael, Goate, Alison, Gray, Emma, Guerreiro, Rita, Gústafsson, Ómar, Hardy, John, Harris, Clare, Hernandez, Dena G., Heutink, Peter, van Hilten, Jacobus J., Hofman, Albert, Hollenbeck, Albert, Holmans, Peter, Holton, Janice, Hu, Michele, Huber, Heiko, Hudson, Gavin, Hunt, Sarah E., Huttenlocher, Johanna, Illig, Thomas, Langford, Cordelia, Lees, Andrew, Lesage, Suzanne, Lichtner, Peter, Limousin, Patricia, Lopez, Grisel, Lorenz, Delia, Martinez, Maria, McNeill, Alisdair, Moorby, Catriona, Moore, Matthew, Morris, Huw, Morrison, Karen E., Moskvina, Valentina, Mudanohwo, Ese, Nalls, Michael A., Pearson, Justin, Perlmutter, Joel S., Pétursson, Hjörvar, Plagnol, Vincent, Pollak, Pierre, Post, Bart, Potter, Simon, Ravina, Bernard, Revesz, Tamas, Riess, Olaf, Rivadeneira, Fernando, Rizzu, Patrizia, Ryten, Mina, Saad, Mohamad, Sawcer, Stephen, Schapira, Anthony, Scheffer, Hans, Sharma, Manu, Shaw, Karen, Sheerin, Una-Marie, Shoulson, Ira, Schulte, Claudia, Sidransky, Ellen, Simón-Sánchez, Javier, Singleton, Andrew B., Smith, Colin, Stefánsson, Hreinn, Stefánsson, Kári, Steinberg, Stacy, Stockton, Joanna D., Sveinbjornsdottir, Sigurlaug, Talbot, Kevin, Tanner, Carlie M., Tashakkori-Ghanbaria, Avazeh, Tison, François, Trabzuni, Daniah, Traynor, Bryan J., Uitterlinden, André G., Velseboer, Daan, Vidailhet, Marie, Walker, Robert, van de Warrenburg, Bart, Wickremaratchi, Mirdhu, Williams, Nigel, Williams-Gray, Caroline H., Winder-Rhodes, Sophie, and Wood, Nicholas

Published
2013
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8. Dissection of the genetics of Parkinsonʼs disease identifies an additional association 5′ of SNCA and multiple associated haplotypes at 17q21

Author

Spencer, Chris C.A., Plagnol, Vincent, Strange, Amy, Gardner, Michelle, Paisan-Ruiz, Coro, Band, Gavin, Barker, Roger A., Bellenguez, Celine, Bhatia, Kailash, Blackburn, Hannah, Blackwell, Jennie M., Bramon, Elvira, Brown, Martin A., Brown, Matthew A., Burn, David, Casas, Juan-Pablo, Chinnery, Patrick F., Clarke, Carl E., Corvin, Aiden, Craddock, Nicholas, Deloukas, Panos, Edkins, Sarah, Evans, Jonathan, Freeman, Colin, Gray, Emma, Hardy, John, Hudson, Gavin, Hunt, Sarah, Jankowski, Janusz, Langford, Cordelia, Lees, Andrew J., Markus, Hugh S., Mathew, Christopher G., McCarthy, Mark I., Morrison, Karen E., Palmer, Colin N.A., Pearson, Justin P., Peltonen, Leena, Pirinen, Matti, Plomin, Robert, Potter, Simon, Rautanen, Anna, Sawcer, Stephen J., Su, Zhan, Trembath, Richard C., Viswanathan, Ananth C., Williams, Nigel W., Morris, Huw R., Donnelly, Peter, and Wood, Nicholas W.

Published
2011
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12. Molecular genetic investigations identify new clinical phenotypes associated with BCS1L-related mitochondrial disease

Author

Oláhová, Monika, primary, Berti, Camilla Ceccatelli, additional, Collier, Jack J, additional, Alston, Charlotte L, additional, Jameson, Elisabeth, additional, Jones, Simon A, additional, Edwards, Noel, additional, He, Langping, additional, Chinnery, Patrick F, additional, Horvath, Rita, additional, Goffrini, Paola, additional, Taylor, Robert W, additional, and Sayer, John A, additional

Published
2019
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13. Mitochondrial DNA sequence characteristics modulate the size of the genetic bottleneck

Author

Wilson, Ian J., primary, Carling, Phillipa J., additional, Alston, Charlotte L., additional, Floros, Vasileios I., additional, Pyle, Angela, additional, Hudson, Gavin, additional, Sallevelt, Suzanne C.E.H., additional, Lamperti, Costanza, additional, Carelli, Valerio, additional, Bindoff, Laurence A., additional, Samuels, David C., additional, Wonnapinij, Passorn, additional, Zeviani, Massimo, additional, Taylor, Robert W., additional, Smeets, Hubert J.M., additional, Horvath, Rita, additional, and Chinnery, Patrick F, additional

Published
2016
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14. Mitochondrial DNA polymerase-gamma and human disease.

Author

Hudson G and Chinnery PF

Subjects
Amino Acid Substitution, Animals, DNA Polymerase gamma, DNA Replication, DNA, Mitochondrial genetics, DNA, Mitochondrial metabolism, DNA-Directed DNA Polymerase genetics, Genes, Dominant, Genes, Recessive, Humans, Infertility, Male enzymology, Infertility, Male genetics, Male, Mice, Mice, Transgenic, Mitochondria genetics, Models, Biological, Mutation, Phenotype, Syndrome, DNA-Directed DNA Polymerase metabolism, Mitochondria enzymology
Abstract

The maintenance of mitochondrial DNA (mtDNA) is critically dependent upon polymerase-gamma (pol-gamma), encoded by the nuclear gene POLG. Over the last 5 years, it has become clear that mutations of POLG are a major cause of human disease. Secondary mtDNA defects characterize these disorders, with mtDNA depletion, multiple mtDNA deletions or multiple point mutations of mtDNA in clinically affected tissues. The secondary mtDNA defects cause cell and tissue-specific deficiencies of mitochondrial oxidative phosphorylation, leading to organ dysfunction and human disease. Functional genetic variants of POLG are present in up to approximately 0.5% of the general population, and pathogenic mutations have been described in most exons of the gene. Clinically, POLG mutations can present from early neonatal life to late middle age, with a spectrum of phenotypes that includes common neurological disorders such as migraine, epilepsy and Parkinsonism. Transgenic mice and biochemical studies of recombinant mutated proteins are helping to unravel mechanisms of pathogenesis, and patterns are beginning to emerge relating genotype to phenotype.

Published
2006
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