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1. ATP6V0C variants impair V-ATPase function causing a neurodevelopmental disorder often associated with epilepsy.

Author

Mattison, Kari, Tossing, Gilles, Mulroe, Fred, Simmons, Callum, Butler, Kameryn, Schreiber, Alison, Alsadah, Adnan, Neilson, Derek, Naess, Karin, Wedell, Anna, Wredenberg, Anna, Sorlin, Arthur, McCann, Emma, Burghel, George, Menendez, Beatriz, Hoganson, George, Botto, Lorenzo, Filloux, Francis, Aledo-Serrano, Ángel, Gil-Nagel, Antonio, Tatton-Brown, Katrina, Verbeek, Nienke, van der Zwaag, Bert, Aleck, Kyrieckos, Fazenbaker, Andrew, Balciuniene, Jorune, Dubbs, Holly, Marsh, Eric, Garber, Kathryn, Ek, Jakob, Duno, Morten, Hoei-Hansen, Christina, Deardorff, Matthew, Raca, Gordana, Quindipan, Catherine, van Hirtum-Das, Michele, Breckpot, Jeroen, Hammer, Trine, Møller, Rikke, Whitney, Andrea, Douglas, Andrew, Kharbanda, Mira, Brunetti-Pierri, Nicola, Morleo, Manuela, Nigro, Vincenzo, May, Halie, Tao, James, Sherr, Elliot, Dobyns, William, Baines, Richard, Warwicker, Jim, Parker, J, Banka, Siddharth, Campeau, Philippe, Escayg, Andrew, and Argilli, Emanuela

Subjects
ATP6V0C, V-ATPase, VMA3, epilepsy genetics, neurodevelopmental disorders, Humans, Vacuolar Proton-Translocating ATPases, Saccharomyces cerevisiae, Epilepsy, Adenosine Triphosphate
Abstract

The vacuolar H+-ATPase is an enzymatic complex that functions in an ATP-dependent manner to pump protons across membranes and acidify organelles, thereby creating the proton/pH gradient required for membrane trafficking by several different types of transporters. We describe heterozygous point variants in ATP6V0C, encoding the c-subunit in the membrane bound integral domain of the vacuolar H+-ATPase, in 27 patients with neurodevelopmental abnormalities with or without epilepsy. Corpus callosum hypoplasia and cardiac abnormalities were also present in some patients. In silico modelling suggested that the patient variants interfere with the interactions between the ATP6V0C and ATP6V0A subunits during ATP hydrolysis. Consistent with decreased vacuolar H+-ATPase activity, functional analyses conducted in Saccharomyces cerevisiae revealed reduced LysoSensor fluorescence and reduced growth in media containing varying concentrations of CaCl2. Knockdown of ATP6V0C in Drosophila resulted in increased duration of seizure-like behaviour, and the expression of selected patient variants in Caenorhabditis elegans led to reduced growth, motor dysfunction and reduced lifespan. In summary, this study establishes ATP6V0C as an important disease gene, describes the clinical features of the associated neurodevelopmental disorder and provides insight into disease mechanisms.

Published
2023

2. British Thoracic Society Guideline for diagnosing and monitoring paediatric sleep-disordered breathing

Author

Evans, Hazel J, primary, Gibson, Neil A, additional, Bennett, Joanna, additional, Chan, Samantha YS, additional, Gavlak, Johanna, additional, Harman, Katharine, additional, Ismail-Koch, Hasnaa, additional, Kingshott, Ruth N, additional, Langley, Ross, additional, Morley, Andrew, additional, Opstad, Kirstie S, additional, Russo, Kylie, additional, Samuels, Martin P, additional, Tan, Hui Leng, additional, Tweedie, Daniel, additional, Yanney, Michael, additional, and Whitney, Andrea, additional

Published
2023
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3. ATP6V0C variants impair V-ATPase function causing a neurodevelopmental disorder often associated with epilepsy

Author

Genetica Klinische Genetica, Mattison, Kari A, Tossing, Gilles, Mulroe, Fred, Simmons, Callum, Butler, Kameryn M, Schreiber, Alison, Alsadah, Adnan, Neilson, Derek E, Naess, Karin, Wedell, Anna, Wredenberg, Anna, Sorlin, Arthur, McCann, Emma, Burghel, George J, Menendez, Beatriz, Hoganson, George E, Botto, Lorenzo D, Filloux, Francis M, Aledo-Serrano, Ángel, Gil-Nagel, Antonio, Tatton-Brown, Katrina, Verbeek, Nienke E, van Hirtum-Das, Michele, Breckpot, Jeroen, Hammer, Trine Bjørg, Møller, Rikke S, Whitney, Andrea, Douglas, Andrew G L, Kharbanda, Mira, Brunetti-Pierri, Nicola, Morleo, Manuela, Nigro, Vincenzo, May, Halie J, Tao, James X, Argili, Emanuela, Sherr, Elliot H, Dobyns, William B, Consortium, Genomics England Research, Baines, Richard A, Warwicker, Jim, Parker, J Alex, Banka, Siddharth, Campeau, Philippe M, Escayg, Andrew, Genetica Klinische Genetica, Mattison, Kari A, Tossing, Gilles, Mulroe, Fred, Simmons, Callum, Butler, Kameryn M, Schreiber, Alison, Alsadah, Adnan, Neilson, Derek E, Naess, Karin, Wedell, Anna, Wredenberg, Anna, Sorlin, Arthur, McCann, Emma, Burghel, George J, Menendez, Beatriz, Hoganson, George E, Botto, Lorenzo D, Filloux, Francis M, Aledo-Serrano, Ángel, Gil-Nagel, Antonio, Tatton-Brown, Katrina, Verbeek, Nienke E, van Hirtum-Das, Michele, Breckpot, Jeroen, Hammer, Trine Bjørg, Møller, Rikke S, Whitney, Andrea, Douglas, Andrew G L, Kharbanda, Mira, Brunetti-Pierri, Nicola, Morleo, Manuela, Nigro, Vincenzo, May, Halie J, Tao, James X, Argili, Emanuela, Sherr, Elliot H, Dobyns, William B, Consortium, Genomics England Research, Baines, Richard A, Warwicker, Jim, Parker, J Alex, Banka, Siddharth, Campeau, Philippe M, and Escayg, Andrew

Published
2023

4. ATP6V0C variants impair V-ATPase function causing a neurodevelopmental disorder often associated with epilepsy

Author

Mattison, Kari A, Tossing, Gilles, Mulroe, Fred, Simmons, Callum, Butler, Kameryn M, Schreiber, Alison, Alsadah, Adnan, Neilson, Derek E, Naess, Karin, Wedell, Anna, Wredenberg, Anna, Sorlin, Arthur, McCann, Emma, Burghel, George J, Menendez, Beatriz, Hoganson, George E, Botto, Lorenzo D, Filloux, Francis M, Aledo-Serrano, Angel, Gil-Nagel, Antonio, Tatton-Brown, Katrina, Verbeek, Nienke E, van der Zwaag, Bert, Aleck, Kyrieckos A, Fazenbaker, Andrew C, Balciuniene, Jorune, Dubbs, Holly A, Marsh, Eric D, Garber, Kathryn, Ek, Jakob, Duno, Morten, Hoei-Hansen, Christina E, Deardorff, Matthew A, Raca, Gordana, Quindipan, Catherine, Van Hirtum-Das, Michele, Breckpot, Jeroen, Hammer, Trine Bjorg, Moller, Rikke S, Whitney, Andrea, Douglas, Andrew GL, Kharbanda, Mira, Brunetti-Pierri, Nicola, Morleo, Manuela, Nigro, Vincenzo, May, Halie J, Tao, James X, Argilli, Emanuela, Sherr, Elliot H, Dobyns, William B, Baines, Richard A, Warwicker, Jim, Parker, J Alex, Banka, Siddharth, Campeau, Philippe M, and Escayg, Andrew

Subjects
neurodevelopmental disorders, ATP6V0C, VMA3, V-ATPase, Neurology (clinical), epilepsy genetics
Abstract

The vacuolar H+-ATPase is an enzymatic complex that functions in an ATP-dependent manner to pump protons across membranes and acidify organelles, thereby creating the proton/pH gradient required for membrane trafficking by several different types of transporters. We describe heterozygous point variants in ATP6V0C, encoding the c-subunit in the membrane bound integral domain of the vacuolar H+-ATPase, in 27 patients with neurodevelopmental abnormalities with or without epilepsy. Corpus callosum hypoplasia and cardiac abnormalities were also present in some patients. In silico modelling suggested that the patient variants interfere with the interactions between the ATP6V0C and ATP6V0A subunits during ATP hydrolysis. Consistent with decreased vacuolar H+-ATPase activity, functional analyses conducted in Saccharomyces cerevisiae revealed reduced LysoSensor fluorescence and reduced growth in media containing varying concentrations of CaCl2. Knockdown of ATP6V0C in Drosophila resulted in increased duration of seizure-like behaviour, and the expression of selected patient variants in Caenorhabditis elegans led to reduced growth, motor dysfunction and reduced lifespan. In summary, this study establishes ATP6V0C as an important disease gene, describes the clinical features of the associated neurodevelopmental disorder and provides insight into disease mechanisms. ispartof: BRAIN vol:146 issue:4 ispartof: location:England status: Published online

Published
2023

7. ATP6V0C variants impair vacuolar V-ATPase causing a neurodevelopmental disorder often associated with epilepsy

Author

Mattison, Kari A, Tossing, Gilles, Mulroe, Fred, Simmons, Callum, Butler, Kameryn M, Schreiber, Alison, Alsadah, Adnan, Neilson, Derek E, Naess, Karin, Wedell, Anna, Wredenberg, Anna, Sorlin, Arthur, McCann, Emma, Burghel, George J, Menendez, Beatriz, Hoganson, George E, Botto, Lorenzo D, Filloux, Francis M, Aledo-Serrano, Ángel, Gil-Nagel, Antonio, Tatton-Brown, Katrina, Verbeek, Nienke E, van Hirtum-Das, Michele, Breckpot, Jeroen, Hammer, Trine Bjørg, Møller, Rikke S, Whitney, Andrea, Douglas, Andrew G L, Kharbanda, Mira, Brunetti-Pierri, Nicola, Morleo, Manuela, Nigro, Vincenzo, May, Halie J, Tao, James X, Argili, Emanuela, Sherr, Elliot H, Dobyns, William B, Consortium, Genomics England Research, Baines, Richard A, Warwicker, Jim, Parker, J Alex, Banka, Siddharth, Campeau, Philippe M, Escayg, Andrew, Mattison, Kari A, Tossing, Gille, Mulroe, Fred, Simmons, Callum, Butler, Kameryn M, Schreiber, Alison, Alsadah, Adnan, Neilson, Derek E, Naess, Karin, Wedell, Anna, Wredenberg, Anna, Sorlin, Arthur, Mccann, Emma, Burghel, George J, Menendez, Beatriz, Hoganson, George E, Botto, Lorenzo D, Filloux, Francis M, Aledo-Serrano, Ángel, Gil-Nagel, Antonio, Tatton-Brown, Katrina, Verbeek, Nienke E, van Hirtum-Das, Michele, Breckpot, Jeroen, Hammer, Trine Bjørg, Møller, Rikke S, Whitney, Andrea, Douglas, Andrew G L, Kharbanda, Mira, Brunetti-Pierri, Nicola, Morleo, Manuela, Nigro, Vincenzo, May, Halie J, Tao, James X, Argili, Emanuela, Sherr, Elliot H, Dobyns, William B, Consortium, Genomics England Research, Baines, Richard A, Warwicker, Jim, Parker, J Alex, Banka, Siddharth, Campeau, Philippe M, and Escayg, Andrew

Subjects
neurodevelopmental disorders, ATP6V0C, VMA3, epilepsy genetic, V-ATPase
Abstract

The vacuolar H+-ATPase (V-ATPase) is an enzymatic complex that functions in an ATP-dependent manner to pump protons across membranes and acidify organelles, thereby creating the proton/pH gradient required for membrane trafficking by several different types of transporters. We describe heterozygous point variants in ATP6V0C, encoding the c-subunit in the membrane bound integral domain of the V-ATPase, in 27 patients with neurodevelopmental abnormalities with or without epilepsy. Corpus callosum hypoplasia and cardiac abnormalities were also present in some patients. In silico modeling suggested that the patient variants interfere with the interactions between the ATP6V0C and ATP6V0A subunits during ATP hydrolysis. Consistent with decreased V-ATPase activity, functional analyses conducted in Saccharomyces cerevisiae revealed reduced LysoSensor fluorescence and reduced growth in media containing varying concentrations of CaCl2. Knockdown of ATP6V0C in Drosophila resulted in increased duration of seizure-like behavior, and the expression of selected patient variants in Caenorhabditis elegans led to reduced growth, motor dysfunction, and reduced lifespan. In summary, this study establishes ATP6V0C as an important disease gene, describes the clinical features of the associated neurodevelopmental disorder, and provides insight into disease mechanisms.

Published
2022

10. Leukoencephalopathy with Calcifications and Cysts: A Purely Neurological Disorder Distinct from Coats Plus

Author

Livingston, John H., Mayer, Josephine, Jenkinson, Emma, Kasher, Paul, Stivaros, Stavros, Berger, Andrea, Cordelli, Duccio M., Ferreira, Patrick, Jefferson, Rosalind, Kutschke, Georg, Lundberg, Staffan, Ounap, Katrin, Prabhakar, Prab, Soh, Calvin, Stewart, Helen, Stone, Jon, van der Knaap, Marjo S., van Esch, Hilda, van Mol, Christine, Wakeling, Emma, Whitney, Andrea, Rice, Gillian I., and Crow, Yanick J.

Published
2014
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11. Intrathecal baclofen pumps in the management of hypertonia in childhood: a UK and Ireland wide survey

Author

Lodh, Rajib, primary, Amin, Sam, additional, Ammar, Amr, additional, Bellis, Lucy, additional, Brink, Phillip, additional, Calisto, Amedeo, additional, Crimmins, Darach, additional, Eunson, Paul, additional, Forsyth, Rob J, additional, Goodden, John, additional, Kaminska, Margaret, additional, Kehoe, Joanne, additional, Kirkpatrick, Martin, additional, Kumar, Ram, additional, Leonard, Jane, additional, Lording, Alice, additional, Martin, Katherine, additional, Miller, Russell, additional, Mordekar, Santosh R, additional, Pettorini, Benedetta, additional, Smith, Martin, additional, Smith, Rachel, additional, Sneade, Christine, additional, Whitney, Andrea, additional, Vloeberghs, Michael, additional, Zaki, Hesham, additional, and Lumsden, Daniel E, additional

Published
2021
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12. An investigation into the relationship between vigabatrin, movement disorders, and brain magnetic resonance imaging abnormalities in children with infantile spasms

Author

Fong, Choong YI, Osborne, John P, Edwards, Stuart W, Hemingway, Cheryl, Hancock, Eleanor, Johnson, Anthony L, Kennedy, Colin R, Kneen, Rachel, Likeman, Marcus, Lux, Andrew L, Mordekar, Santosh R, Murugan, Velayutham, Newton, Richard W, Pike, Michael, Quinn, Michael, Spinty, Stefan, Vassallo, Grace, Verity, Christopher M, Whitney, Andrea, and OʼCallaghan, Finbar J K

Published
2013
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15. Leukoencephalopathy with calcifications and cysts: Genetic and phenotypic spectrum

Author

Crow, Yanick J, primary, Marshall, Heather, additional, Rice, Gillian I, additional, Seabra, Luis, additional, Jenkinson, Emma M, additional, Baranano, Kristin, additional, Battini, Roberta, additional, Berger, Andrea, additional, Blair, Edward, additional, Blauwblomme, Thomas, additional, Bolduc, Francois, additional, Boddaert, Natalie, additional, Buckard, Johannes, additional, Burnett, Heather, additional, Calvert, Sophie, additional, Caumes, Roseline, additional, Ng, Andy Cheuk‐Him, additional, Chiang, Diana, additional, Clifford, David B, additional, Cordelli, Duccio M, additional, Burca, Anna, additional, Demic, Natasha, additional, Desguerre, Isabelle, additional, De Waele, Liesbeth, additional, Di Fonzo, Alessio, additional, Dunham, S. Richard, additional, Dyack, Sarah, additional, Elmslie, Frances, additional, Ferrand, Mickaël, additional, Fisher, Gemma, additional, Karimiani, Ehsan Ghayoor, additional, Ghoumid, Jamal, additional, Gibbon, Frances, additional, Goel, Himanshu, additional, Hilmarsen, Hilde T, additional, Hughes, Imelda, additional, Jacob, Anu, additional, Jones, Elizabeth A, additional, Kumar, Ram, additional, Leventer, Richard J, additional, MacDonald, Shelley, additional, Maroofian, Reza, additional, Mehta, Sarju G, additional, Metz, Imke, additional, Monfrini, Edoardo, additional, Neumann, Daniela, additional, Noetzel, Michael, additional, O'Driscoll, Mary, additional, Õunap, Katrin, additional, Panzer, Axel, additional, Parikh, Sumit, additional, Prabhakar, Prab, additional, Ramond, Francis, additional, Sandford, Richard, additional, Saneto, Russell, additional, Soh, Calvin, additional, Stutterd, Chloe A, additional, Subramanian, Gopinath M, additional, Talbot, Kevin, additional, Thomas, Rhys H, additional, Toro, Camilo, additional, Touraine, Renaud, additional, Wakeling, Emma, additional, Wassmer, Evangeline, additional, Whitney, Andrea, additional, Livingston, John H, additional, O'Keefe, Raymond T, additional, and Badrock, Andrew P, additional

Published
2020
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20. Vigabatrin with hormonal treatment versus hormonal treatment alone (ICISS) for infantile spasms: 18-month outcomes of an open-label, randomised controlled trial

Author

O'Callaghan, Finbar J K, primary, Edwards, Stuart W, additional, Alber, Fabienne Dietrich, additional, Cortina Borja, Mario, additional, Hancock, Eleanor, additional, Johnson, Anthony L, additional, Kennedy, Colin R, additional, Likeman, Marcus, additional, Lux, Andrew L, additional, Mackay, Mark T, additional, Mallick, Andrew A, additional, Newton, Richard W, additional, Nolan, Melinda, additional, Pressler, Ronit, additional, Rating, Dietz, additional, Schmitt, Bernhard, additional, Verity, Christopher M, additional, Osborne, John P, additional, Abdel Aziz, Maysara, additional, Acharya, Triloknath, additional, Adcock, Carolyn, additional, Jones, Robert, additional, Howells, Rachel, additional, Marsh, Ben, additional, Adejare, Kemi, additional, Adiga, Rashmi, additional, Wheater, Mary, additional, Ahmed, Mansoor, additional, Sawal, Mohammad, additional, Goel, Chhavi, additional, Ahmed, MAS, additional, Alber, Michael, additional, Wolff, Markus, additional, Ruf, Susanne, additional, Al-Kharusi, Asya, additional, Al-Moasseb, Hassan, additional, Arora, Ruchi, additional, Beach, Richard, additional, Atkinson, Patricia, additional, Ayonrinde, Kunle, additional, Bala, Pronab, additional, Bamford, Nicola, additional, Barakat, Nagi, additional, Basheer, Nigel, additional, Baxter, Peter, additional, Mordekar, Santosh, additional, Rittey, Chris, additional, Borggraefe, Ingo, additional, Borusiak, Peter, additional, Cagnoli, Sabine, additional, Brown, Richard, additional, Calvert, Sophie, additional, Cameron, Duncan, additional, Chaniyil, Ramesh, additional, Chinthapalli, Ravi, additional, Chow, Gabriel, additional, Whitehouse, William, additional, Clarke, Vinodhini, additional, Cooper, Chris, additional, Datta, Alexane, additional, D'Costa, Selwyn, additional, de Goede, Christian, additional, Basu, Helen, additional, Deekollu, David, additional, Della Marina, Adela, additional, Dison, Penelope, additional, Dunkley, Colin, additional, Eaton, Megan, additional, Ellison, Julie, additional, Pugh, Robert, additional, Fallon, Penny, additional, Faza, Hani, additional, Choonara, Imti, additional, Morton, Richard, additional, Ratnayaka, Mal, additional, Ferrie, Colin, additional, Freeman, Amanda, additional, Warriner, Stephen, additional, Garcia, Maria, additional, Ghazavi, Malihe, additional, Gibbon, Frances, additional, Gibbs, John, additional, Ginbey, Des, additional, Guarino, Iolanda, additional, Gupta, Rajesh, additional, Hanlon, Mary, additional, Harris, Siân, additional, Munyard, Paul, additional, Hemingway, Cheryl, additional, Eltze, Christin, additional, Kaliakatsos, Marios, additional, Murugan, Velayutham, additional, Robinson, Robert, additional, Tan, Jeen, additional, Hindley, Daniel, additional, Hughes, Adrian, additional, Hussain, Akmal, additional, Boden, Greg, additional, Hussain, Munir, additional, Hussain, Nahin, additional, Dabydeen, Lyvia, additional, Irwin, Kate, additional, Jacobs, Julia, additional, Jauhari, Praveen, additional, Minchom, Philip, additional, Jones, Simon, additional, Karenfort, Michael, additional, Keimer, Reinhard, additional, Kennedy, Colin, additional, Kirkham, Fenella, additional, Whitney, Andrea, additional, Kirkpatrick, Martin, additional, Jollands, Alice, additional, Kneen, Rachel, additional, Iyer, Anand, additional, McTague, Amy, additional, Spinty, Stefan, additional, Kumar, Ramesh, additional, Kurlemann, Gerhard, additional, Lee, Matthew, additional, Jurges, Eman, additional, Levy, Robert, additional, Lewis, Helen, additional, Lewis, Hilary, additional, Lloyd Evans, Andrew, additional, Loh, Ne-Ron, additional, Osborne, John, additional, O'Callaghan, Finbar, additional, Maddicks, Hilary, additional, Luecke, Thomas, additional, Lux, Andrew, additional, Majumdar, Anirban, additional, Vijayakumar, Kayal, additional, MacKay, Mark, additional, Freeman, Jeremy, additional, Hayman, Michael, additional, Kornberg, Andrew, additional, Leventer, Rick, additional, Ryan, Monique, additional, Ware, Tyson, additional, Mancais, Penny, additional, Marinaki, Katina, additional, Massarano, Albert, additional, Mathew, Satheesh, additional, McLellan, Ailsa, additional, Melville, Colin, additional, Mewasingh, Leena, additional, Muhle, Hiltrud, additional, Nagmeldin, Eisawi, additional, Natarajan, Jeyashree, additional, Nelapatla, Suresh, additional, Gondwe, Jailosi, additional, Newton, Richard, additional, Hughes, Imelda, additional, Martland, Tim, additional, McCullagh, Gary, additional, Vassallo, Grace, additional, Nirmal, Stephen, additional, Davis, Suzanne, additional, Patel, Rakesh, additional, Sharpe, Cynthia, additional, Olabi, Anas, additional, O'Neill, Kevin, additional, Gould, Jim, additional, Panzer, Axel, additional, Theophil, Manuela, additional, Parepalli, Srinivas, additional, Hinde, Frank, additional, Smith, Martin, additional, Parker, Alasdair, additional, Chitre, Manali, additional, Philip, Sunny, additional, Gupta, Rajat, additional, Wassmer, Evangeline, additional, Pike, Mike, additional, McShane, Tony, additional, Prakash, Nandhini, additional, Padmakumar, Beena, additional, Pridmore, Clair, additional, Prietsch, Viola, additional, Krieg, Peter, additional, Quinlivan, Ros, additional, Quinn, Michael, additional, Collinson, Andrew, additional, Rajalingam, Usha, additional, Rakshi, Karl, additional, Rao, Tekki, additional, Ravi, Asha, additional, Rifkin, Rob, additional, Roper, Helen, additional, Rowlandson, Piers, additional, Sadleir, Lynette, additional, Sahi, Sanjay, additional, Saraswatula, Arun, additional, O'Sullivan, Siobhan, additional, Saravanan, Kethar, additional, Scammell, Alastair, additional, Rao, Sudhakar, additional, Schubert-Bast, Susanne, additional, Scott, David J, additional, Scott, Fraser, additional, Pye, Matthew, additional, Shah, Ayaz, additional, Stephen, Elma, additional, Shah, Shambhu, additional, Butterfill, Andrew, additional, Shute, Pauline, additional, Singh, Rajeeva, additional, Allogoa, Brigid, additional, Singh, Ravinder, additional, Sinha, Gyanranjan, additional, Sivakumar, Puthuval, additional, Smith, Robert, additional, Sriskandan, Sivaranjini, additional, Steinert, Martin, additional, Strassburg, Michael, additional, Strozzi, Susi, additional, Subramanian, Geeta, additional, and Tandy, Andrew, additional

Published
2018
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21. Erratum: Corrigendum: Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts

Author

Jenkinson, Emma M, primary, Rodero, Mathieu P, additional, Kasher, Paul R, additional, Uggenti, Carolina, additional, Oojageer, Anthony, additional, Goosey, Laurence C, additional, Rose, Yoann, additional, Kershaw, Christopher J, additional, Urquhart, Jill E, additional, Williams, Simon G, additional, Bhaskar, Sanjeev S, additional, O'Sullivan, James, additional, Baerlocher, Gabriela M, additional, Haubitz, Monika, additional, Aubert, Geraldine, additional, Barañano, Kristin W, additional, Barnicoat, Angela J, additional, Battini, Roberta, additional, Berger, Andrea, additional, Blair, Edward M, additional, Brunstrom-Hernandez, Janice E, additional, Buckard, Johannes A, additional, Cassiman, David M, additional, Caumes, Rosaline, additional, Cordelli, Duccio M, additional, De Waele, Liesbeth M, additional, Fay, Alexander J, additional, Ferreira, Patrick, additional, Fletcher, Nicholas A, additional, Fryer, Alan E, additional, Goel, Himanshu, additional, Hemingway, Cheryl A, additional, Henneke, Marco, additional, Hughes, Imelda, additional, Jefferson, Rosalind J, additional, Kumar, Ram, additional, Lagae, Lieven, additional, Landrieu, Pierre G, additional, Lourenço, Charles M, additional, Malpas, Timothy J, additional, Mehta, Sarju G, additional, Metz, Imke, additional, Naidu, Sakkubai, additional, Õunap, Katrin, additional, Panzer, Axel, additional, Prabhakar, Prab, additional, Quaghebeur, Gerardine, additional, Schiffmann, Raphael, additional, Sherr, Elliott H, additional, Sinnathuray, Kanaga R, additional, Soh, Calvin, additional, Stewart, Helen S, additional, Stone, John, additional, Van Esch, Hilde, additional, Van Mol, Christine E G, additional, Vanderver, Adeline, additional, Wakeling, Emma L, additional, Whitney, Andrea, additional, Pavitt, Graham D, additional, Griffiths-Jones, Sam, additional, Rice, Gillian I, additional, Revy, Patrick, additional, van der Knaap, Marjo S, additional, Livingston, John H, additional, O'Keefe, Raymond T, additional, and Crow, Yanick J, additional

Published
2017
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22. Actually Appetizing

Author

Whitney, Andrea

Subjects
Wellness programs -- Evaluation, Occupational health and safety -- Evaluation, Business, Human resources and labor relations
Abstract

Byline: Andrea Whitney I can vividly recall sitting in the kitchen, listening to the garbling fuzz-buzz-beep-beep of my dial-up connection while saying, 'It works just fine. I don't need to [...]

Published
2012

23. Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts

Author

Jenkinson, Emma M, primary, Rodero, Mathieu P, additional, Kasher, Paul R, additional, Uggenti, Carolina, additional, Oojageer, Anthony, additional, Goosey, Laurence C, additional, Rose, Yoann, additional, Kershaw, Christopher J, additional, Urquhart, Jill E, additional, Williams, Simon G, additional, Bhaskar, Sanjeev S, additional, O'Sullivan, James, additional, Baerlocher, Gabriela M, additional, Haubitz, Monika, additional, Aubert, Geraldine, additional, Barañano, Kristin W, additional, Barnicoat, Angela J, additional, Battini, Roberta, additional, Berger, Andrea, additional, Blair, Edward M, additional, Brunstrom-Hernandez, Janice E, additional, Buckard, Johannes A, additional, Cassiman, David M, additional, Caumes, Rosaline, additional, Cordelli, Duccio M, additional, De Waele, Liesbeth M, additional, Fay, Alexander J, additional, Ferreira, Patrick, additional, Fletcher, Nicholas A, additional, Fryer, Alan E, additional, Goel, Himanshu, additional, Hemingway, Cheryl A, additional, Henneke, Marco, additional, Hughes, Imelda, additional, Jefferson, Rosalind J, additional, Kumar, Ram, additional, Lagae, Lieven, additional, Landrieu, Pierre G, additional, Lourenço, Charles M, additional, Malpas, Timothy J, additional, Mehta, Sarju G, additional, Metz, Imke, additional, Naidu, Sakkubai, additional, Õunap, Katrin, additional, Panzer, Axel, additional, Prabhakar, Prab, additional, Quaghebeur, Gerardine, additional, Schiffmann, Raphael, additional, Sherr, Elliott H, additional, Sinnathuray, Kanaga R, additional, Soh, Calvin, additional, Stewart, Helen S, additional, Stone, John, additional, Van Esch, Hilde, additional, Van Mol, Christine E G, additional, Vanderver, Adeline, additional, Wakeling, Emma L, additional, Whitney, Andrea, additional, Pavitt, Graham D, additional, Griffiths-Jones, Sam, additional, Rice, Gillian I, additional, Revy, Patrick, additional, van der Knaap, Marjo S, additional, Livingston, John H, additional, O'Keefe, Raymond T, additional, and Crow, Yanick J, additional

Published
2016
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24. Revenue Assurance: Another CLEC Challenge

Author

Geppert, Carl and Whitney, Andrea

Subjects
Company business planning, Local telephone service, Telecommunications services industry, Market trend/market analysis, Telephone services -- Forecasts and trends -- Planning, Telecommunications services industry -- Planning -- Forecasts and trends, Local telephone services -- Forecasts and trends -- Planning, Communications industry -- Planning -- Forecasts and trends
Abstract

In the CLEC market, a comprehensive revenue assurance process is a strategic weapon. Revenue assurance is the program of activities that an organization undertakes to ensure that its processes, practices […]

Published
1999

25. Leukoencephalopathy with Calcifications and Cysts : A Purely Neurological Disorder Distinct from Coats Plus

Author

Livingston, John H, Mayer, Josephine, Jenkinson, Emma, Kasher, Paul, Stivaros, Stavros, Berger, Andrea, Cordelli, Duccio M, Ferreira, Patrick, Jefferson, Rosalind, Kutschke, Georg, Lundberg, Staffan, Ounap, Katrin, Prabhakar, Prab, Soh, Calvin, Stewart, Helen, Stone, Jon, van der Knaap, Marjo S, van Esch, Hilda, van Mol, Christine, Wakeling, Emma, Whitney, Andrea, Rice, Gillian I, Crow, Yanick J, Livingston, John H, Mayer, Josephine, Jenkinson, Emma, Kasher, Paul, Stivaros, Stavros, Berger, Andrea, Cordelli, Duccio M, Ferreira, Patrick, Jefferson, Rosalind, Kutschke, Georg, Lundberg, Staffan, Ounap, Katrin, Prabhakar, Prab, Soh, Calvin, Stewart, Helen, Stone, Jon, van der Knaap, Marjo S, van Esch, Hilda, van Mol, Christine, Wakeling, Emma, Whitney, Andrea, Rice, Gillian I, and Crow, Yanick J

Abstract

Objective With the identification of mutations in the conserved telomere maintenance component 1 (CTC1) gene as the cause of Coats plus (CP) disease, it has become evident that leukoencephalopathy with calcifications and cysts (LCC) is a distinct genetic entity. Patients and Methods A total of 15 patients with LCC were identified from our database of patients with intracranial calcification. The clinical and radiological features are described. Results The median age (range) at presentation was 10 months (range, 2 days-54 years). Of the 15 patients, 9 presented with epileptic seizures, 5 with motor abnormalities, and 1 with developmental delay. Motor abnormalities developed in 14 patients and cognitive problems in 13 patients. Dense calcification occurred in the basal ganglia, thalami, dentate nucleus, brain stem, deep gyri, deep white matter, and in a pericystic distribution. Diffuse leukoencephalopathy was present in all patients, and it was usually symmetrical involving periventricular, deep, and sometimes subcortical, regions. Cysts developed in the basal ganglia, thalamus, deep white matter, cerebellum, or brain stem. In unaffected areas, normal myelination was present. No patient demonstrated cerebral atrophy. Conclusion LCC shares the neuroradiological features of CP. However, LCC is a purely neurological disorder distinguished genetically by the absence of mutations in CTC1. The molecular cause(s) of LCC has (have) not yet been determined.

Published
2014
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27. Leukoencephalopathy with Calcifications and Cysts: A Purely Neurological Disorder Distinct from Coats Plus

Author

Mayer, Josephine, primary, Jenkinson, Emma, primary, Kasher, Paul, primary, Stivaros, Stavros, primary, Berger, Andrea, primary, Cordelli, Duccio, primary, Ferreira, Patrick, primary, Jefferson, Rosalind, primary, Kutschke, Georg, primary, Lundberg, Staffan, primary, Ounap, Katrin, primary, Prabhakar, Prab, primary, Soh, Calvin, primary, Stewart, Helen, primary, Stone, Jon, primary, van der Knaap, Marjo, primary, van Esch, Hilda, primary, van Mol, Christine, primary, Wakeling, Emma, primary, Whitney, Andrea, primary, Rice, Gillian, primary, Crow, Yanick, primary, and Livingston, John, additional

Published
2014
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28. Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus

Author

Anderson, Beverley H., Kasher, Paul R., Mayer, Josephine, Szynkiewicz, Marcin, Jenkinson, Emma M., Bhaskar, Sanjeev S., Urquhart, Jill E., Daly, Sarah B., Dickerson, Jonathan E., O'Sullivan, James, Leibundgut, Elisabeth Oppliger, Muter, Joanne, Abdel-Salem, Ghada M. H., Babul-Hirji, Riyana, Baxter, Peter, Berger, Andrea, Bonafe, Luisa, Brunstom-Hernandez, Janice E., Buckard, Johannes A., Chitayat, David, Chong, Wui K., Cordelli, Duccio M., Ferreira, Patrick, Fluss, Joel, Forrest, Ewan H., Franzoni, Emilio, Garone, Caterina, Hammans, Simon R., Houge, Gunnar, Hughes, Imelda, Jacquemont, Sebastien, Jeannet, Pierre-Yves, Jefferson, Rosalind J., Kumar, Ram, Kutschke, Georg, Lundberg, Staffan, Lourenco, Charles M., Mehta, Ramesh, Naidu, Sakkubai, Nischal, Ken K., Nunes, Luis, Ounap, Katrin, Philippart, Michel, Prabhakar, Prab, Risen, Sarah R., Schiffmann, Raphael, Soh, Calvin, Stephenson, John B. P., Stewart, Helen, Stone, Jon, Tolmie, John L., van der Knaap, Marjo S., Vieira, Jose P., Vilain, Catheline N., Wakeling, Emma L., Wermenbol, Vanessa, Whitney, Andrea, Lovell, Simon C., Meyer, Stefan, Livingston, John H., Baerlocher, Gabriela M., Black, Graeme C. M., Rice, Gillian I., Crow, Yanick J., Anderson, Beverley H., Kasher, Paul R., Mayer, Josephine, Szynkiewicz, Marcin, Jenkinson, Emma M., Bhaskar, Sanjeev S., Urquhart, Jill E., Daly, Sarah B., Dickerson, Jonathan E., O'Sullivan, James, Leibundgut, Elisabeth Oppliger, Muter, Joanne, Abdel-Salem, Ghada M. H., Babul-Hirji, Riyana, Baxter, Peter, Berger, Andrea, Bonafe, Luisa, Brunstom-Hernandez, Janice E., Buckard, Johannes A., Chitayat, David, Chong, Wui K., Cordelli, Duccio M., Ferreira, Patrick, Fluss, Joel, Forrest, Ewan H., Franzoni, Emilio, Garone, Caterina, Hammans, Simon R., Houge, Gunnar, Hughes, Imelda, Jacquemont, Sebastien, Jeannet, Pierre-Yves, Jefferson, Rosalind J., Kumar, Ram, Kutschke, Georg, Lundberg, Staffan, Lourenco, Charles M., Mehta, Ramesh, Naidu, Sakkubai, Nischal, Ken K., Nunes, Luis, Ounap, Katrin, Philippart, Michel, Prabhakar, Prab, Risen, Sarah R., Schiffmann, Raphael, Soh, Calvin, Stephenson, John B. P., Stewart, Helen, Stone, Jon, Tolmie, John L., van der Knaap, Marjo S., Vieira, Jose P., Vilain, Catheline N., Wakeling, Emma L., Wermenbol, Vanessa, Whitney, Andrea, Lovell, Simon C., Meyer, Stefan, Livingston, John H., Baerlocher, Gabriela M., Black, Graeme C. M., Rice, Gillian I., and Crow, Yanick J.

Abstract

Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous gamma H2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the alpha-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-alpha primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.

Published
2012
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31. Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus

Author

Anderson, Beverley H, primary, Kasher, Paul R, additional, Mayer, Josephine, additional, Szynkiewicz, Marcin, additional, Jenkinson, Emma M, additional, Bhaskar, Sanjeev S, additional, Urquhart, Jill E, additional, Daly, Sarah B, additional, Dickerson, Jonathan E, additional, O'Sullivan, James, additional, Leibundgut, Elisabeth Oppliger, additional, Muter, Joanne, additional, Abdel-Salem, Ghada M H, additional, Babul-Hirji, Riyana, additional, Baxter, Peter, additional, Berger, Andrea, additional, Bonafé, Luisa, additional, Brunstom-Hernandez, Janice E, additional, Buckard, Johannes A, additional, Chitayat, David, additional, Chong, Wui K, additional, Cordelli, Duccio M, additional, Ferreira, Patrick, additional, Fluss, Joel, additional, Forrest, Ewan H, additional, Franzoni, Emilio, additional, Garone, Caterina, additional, Hammans, Simon R, additional, Houge, Gunnar, additional, Hughes, Imelda, additional, Jacquemont, Sebastien, additional, Jeannet, Pierre-Yves, additional, Jefferson, Rosalind J, additional, Kumar, Ram, additional, Kutschke, Georg, additional, Lundberg, Staffan, additional, Lourenço, Charles M, additional, Mehta, Ramesh, additional, Naidu, Sakkubai, additional, Nischal, Ken K, additional, Nunes, Luís, additional, Õunap, Katrin, additional, Philippart, Michel, additional, Prabhakar, Prab, additional, Risen, Sarah R, additional, Schiffmann, Raphael, additional, Soh, Calvin, additional, Stephenson, John B P, additional, Stewart, Helen, additional, Stone, Jon, additional, Tolmie, John L, additional, van der Knaap, Marjo S, additional, Vieira, Jose P, additional, Vilain, Catheline N, additional, Wakeling, Emma L, additional, Wermenbol, Vanessa, additional, Whitney, Andrea, additional, Lovell, Simon C, additional, Meyer, Stefan, additional, Livingston, John H, additional, Baerlocher, Gabriela M, additional, Black, Graeme C M, additional, Rice, Gillian I, additional, and Crow, Yanick J, additional

Published
2012
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34. Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts (vol 48, pg 1185, 2016)

Author

Jenkinson, Emma M., Rodero, Mathieu P., Kasher, Paul R., Uggenti, Carolina, Oojageer, Anthony, Goosey, Laurence C., Rose, Yoann, Kershaw, Christopher J., Urquhart, Jill E., Williams, Simon G., Bhaskar, Sanjeev S., O Sullivan, James, Baerlocher, Gabriela M., Haubitz, Monika, Aubert, Geraldine, Baranano, Kristin W., Barnicoat, Angela J., Battini, Roberta, Berger, Andrea, Blair, Edward M., Brunstrom-Hernandez, Janice E., Buckard, Johannes A., Cassiman, David M., Caumes, Rosaline, Cordelli, Duccio M., Waele, Liesbeth M., Fay, Alexander J., Ferreira, Patrick, Fletcher, Nicholas A., Fryer, Alan E., Goel, Himanshu, Hemingway, Cheryl A., Henneke, Marco, Hughes, Imelda, Jefferson, Rosalind J., Kumar, Ram, Lagae, Lieven, Landrieu, Pierre G., Lourenco, Charles M., Malpas, Timothy J., Mehta, Sarju G., Metz, Imke, Naidu, Sakkubai, Ounap, Katrin, Panzer, Axel, Prabhakar, Prab, Quaghebeur, Gerardine, Schiffmann, Raphael, Sherr, Elliott H., Sinnathuray, Kanaga R., Soh, Calvin, Stewart, Helen S., Stone, John, Esch, Hilde, Mol, Christine E. G., Vanderver, Adeline, Wakeling, Emma L., Whitney, Andrea, Graham Pavitt, Griffiths-Jones, Sam, Rice, Gillian I., Revy, Patrick, Knaap, Marjo S., Livingston, John H., O Keefe, Raymond T., Crow, Yanick J., Other departments, and Paediatric Neurology

35. Corrigendum: Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts

Author

Jenkinson, Emma M, Rodero, Mathieu P, Kasher, Paul R, Uggenti, Carolina, Oojageer, Anthony, Goosey, Laurence C, Rose, Yoann, Kershaw, Christopher J, Urquhart, Jill E, Williams, Simon G, Bhaskar, Sanjeev S, O'Sullivan, James, Baerlocher, Gabriela M, Haubitz, Monika, Aubert, Geraldine, Barañano, Kristin W, Barnicoat, Angela J, Battini, Roberta, Berger, Andrea, Blair, Edward M, Brunstrom-Hernandez, Janice E, Buckard, Johannes A, Cassiman, David M, Caumes, Rosaline, Cordelli, Duccio M, De Waele, Liesbeth M, Fay, Alexander J, Ferreira, Patrick, Fletcher, Nicholas A, Fryer, Alan E, Goel, Himanshu, Hemingway, Cheryl A, Henneke, Marco, Hughes, Imelda, Jefferson, Rosalind J, Kumar, Ram, Lagae, Lieven, Landrieu, Pierre G, Lourenço, Charles M, Malpas, Timothy J, Mehta, Sarju G, Metz, Imke, Naidu, Sakkubai, Õunap, Katrin, Panzer, Axel, Prabhakar, Prab, Quaghebeur, Gerardine, Schiffmann, Raphael, Sherr, Elliott H, Sinnathuray, Kanaga R, Soh, Calvin, Stewart, Helen S, Stone, John, Van Esch, Hilde, Van Mol, Christine E G, Vanderver, Adeline, Wakeling, Emma L, Whitney, Andrea, Pavitt, Graham D, Griffiths-Jones, Sam, Rice, Gillian I, Revy, Patrick, van der Knaap, Marjo S, Livingston, John H, O'Keefe, Raymond T, and Crow, Yanick J

Published
2017
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36. Surgery for childhood epilepsy.

Author

Whitney, Andrea and Cross, Helen

Abstract

The article focuses on the neurosurgical techniques which could be employed to manage epilepsy in children in Great Britain. Surgery is thought to improve developmental potential, so that even children with profound learning disability may experience significant improvements in quality of life. Two types of procedure are offered in epilepsy surgery, one is resective procedure and the other is functional procedures.

Published
2007

37. Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts

Author

Elliott H. Sherr, Edward Blair, Charles Marques Lourenço, James O'Sullivan, Imke Metz, Paul R. Kasher, Gabriela M. Baerlocher, Adeline Vanderver, David Cassiman, Himanshu Goel, Nicholas A. Fletcher, Patrick Ferreira, Patrick Revy, Emma Wakeling, Ram L. Kumar, Lieven Lagae, Christopher J. Kershaw, Pierre Landrieu, Andrea Whitney, Calvin Soh, Christine E. G. van Mol, Sakkubai Naidu, John H. Livingston, Geraldine Aubert, H. Stewart, Laurence C. Goosey, Liesbeth De Waele, Kristin W. Barañano, Rosalind J. Jefferson, Axel Panzer, Gerardine Quaghebeur, Raphael Schiffmann, Yanick J. Crow, Hilde Van Esch, Raymond T. O'Keefe, Jill E. Urquhart, Alan Fryer, Mathieu P Rodero, Alex J. Fay, Monika Haubitz, Andrea Berger, Johannes A. Buckard, Cheryl Hemingway, Angela Barnicoat, Sam Griffiths-Jones, Duccio Maria Cordelli, Imelda Hughes, Katrin Õunap, Graham D. Pavitt, Roberta Battini, Yoann Rose, Marjo S. van der Knaap, Sanjeev S. Bhaskar, John Stone, Gillian I. Rice, Marco Henneke, Kanaga R. Sinnathuray, Emma M. Jenkinson, Timothy J. Malpas, Simon G. Williams, Anthony Oojageer, Carolina Uggenti, Rosaline Caumes, Prab Prabhakar, Sarju G. Mehta, Janice E. Brunstrom-Hernandez, Manchester Centre for Genomic Medicine (MCGM), Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester]-University of Manchester [Manchester]-Faculty of Biology, Medicine and Health [Manchester, UK], University of Manchester [Manchester]-Manchester University NHS Foundation Trust (MFT)-St Mary's Hospital Manchester, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Manchester [Manchester], Department of Medical Genetics, HMNC Brain Health, Other departments, Jenkinson, Emma M., Rodero, Mathieu P., Kasher, Paul R., Uggenti, Carolina, Oojageer, Anthony, Goosey, Laurence C., Rose, Yoann, Kershaw, Christopher J., Urquhart, Jill E., Williams, Simon G., Bhaskar, Sanjeev S., O'Sullivan, Jame, Baerlocher, Gabriela M., Haubitz, Monika, Aubert, Geraldine, Barañano, Kristin W., Barnicoat, Angela J., Battini, Roberta, Berger, Andrea, Blair, Edward M., Brunstrom-Hernandez, Janice E., Buckard, Johannes A., Cassiman, David M., Caumes, Rosaline, Cordelli, Duccio M., De Waele, Liesbeth M., Fay, Alexander J., Ferreira, Patrick, Fletcher, Nicholas A., Fryer, Alan E., Goel, Himanshu, Hemingway, Cheryl A., Henneke, Marco, Hughes, Imelda, Jefferson, Rosalind J., Kumar, Ram, Lagae, Lieven, Landrieu, Pierre G., Lourenço, Charles M., Malpas, Timothy J., Mehta, Sarju G., Metz, Imke, Naidu, Sakkubai, Õunap, Katrin, Panzer, Axel, Prabhakar, Prab, Quaghebeur, Gerardine, Schiffmann, Raphael, Sherr, Elliott H., Sinnathuray, Kanaga R., Soh, Calvin, Stewart, Helen S., Stone, John, Van Esch, Hilde, Van Mol, Christine E. G., Vanderver, Adeline, Wakeling, Emma L., Whitney, Andrea, Pavitt, Graham D., Griffiths-Jones, Sam, Rice, Gillian I., Revy, Patrick, Van Der Knaap, Marjo S., Livingston, John H., O'Keefe, Raymond T., Crow, Yanick J., Pediatric surgery, and Amsterdam Neuroscience - Cellular & Molecular Mechanisms

Subjects
0301 basic medicine, Male, Genetic Linkage, [SDV]Life Sciences [q-bio], Ribosome biogenesis, medicine.disease_cause, Leukoencephalopathy, Leukoencephalopathie, Cohort Studies, 0302 clinical medicine, Leukoencephalopathies, Exome, Small nucleolar RNA, 610 Medicine & health, Child, ComputingMilieux_MISCELLANEOUS, Genetics, Mutation, Genome, Cysts, Calcinosis, Middle Aged, Phenotype, Child, Preschool, Calcinosi, Female, Sequence Analysis, Human, Adult, Adolescent, Biology, Chromosomes, Cell Line, 03 medical and health sciences, Young Adult, medicine, RNA, Small Nucleolar, Humans, Preschool, Gene, Small Nucleolar, Genome, Human, Pair 17, RNA, Infant, Sequence Analysis, DNA, DNA, Cerebral Small Vessel Diseases, Chromosomes, Human, Pair 17, medicine.disease, Cerebral Small Vessel Disease, 030104 developmental biology, Cyst, Cohort Studie, 030217 neurology & neurosurgery
Abstract

Although ribosomes are ubiquitous and essential for life, recent data indicate that monogenic causes of ribosomal dysfunction can confer a remarkable degree of specificity in terms of human disease phenotype. Box C/D small nucleolar RNAs (snoRNAs) are evolutionarily conserved non-protein-coding RNAs involved in ribosome biogenesis. Here we show that biallelic mutations in the gene SNORD118, encoding the box C/D snoRNA U8, cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts (LCC), presenting at any age from early childhood to late adulthood. These mutations affect U8 expression, processing and protein binding and thus implicate U8 as essential in cerebral vascular homeostasis.

Published
2016

38. Leukoencephalopathy with Calcifications and Cysts: A Purely Neurological Disorder Distinct from Coats Plus

Author

Andrea Berger, Katrin Õunap, Paul R. Kasher, Yanick J. Crow, Emma M. Jenkinson, Duccio Maria Cordelli, Emma Wakeling, Helen Stewart, Andrea Whitney, John H. Livingston, Calvin Soh, Patrick Ferreira, Christine E. G. van Mol, Staffan Lundberg, Stavros Stivaros, Josephine Mayer, Rosalind J. Jefferson, Prab Prabhakar, Jon Stone, Georg Kutschke, Gillian I. Rice, Marjo S. van der Knaap, Hilda van Esch, Other departments, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Pediatric surgery, NCA - Brain mechanisms in health and disease, Livingston, John H., Mayer, Josephine, Jenkinson, Emma, Kasher, Paul, Stivaros, Stavro, Berger, Andrea, Cordelli, Duccio M., Ferreira, Patrick, Jefferson, Rosalind, Kutschke, Georg, Lundberg, Staffan, Ounap, Katrin, Prabhakar, Prab, Soh, Calvin, Stewart, Helen, Stone, Jon, Van Der Knaap, Marjo S., Van Esch, Hilda, Van Mol, Christine, Wakeling, Emma, Whitney, Andrea, Rice, Gillian I., and Crow, Yanick J.

Subjects
Adult, leukoencephalopathy, Cerebellum, Pathology, medicine.medical_specialty, Tomography Scanners, X-Ray Computed, Adolescent, coats plu, Neurological disorder, intracranial calcification, Leukoencephalopathie, Leukoencephalopathy, White matter, Young Adult, Leukoencephalopathies, Basal ganglia, Humans, Medicine, Child, Nervous System Disease, Cerebral atrophy, Brain Diseases, Cysts, business.industry, Brain Disease, Infant, Newborn, Calcinosis, Infant, General Medicine, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Cyst, medicine.anatomical_structure, Dentate nucleus, Child, Preschool, Pediatrics, Perinatology and Child Health, Calcinosi, Neurology (clinical), Nervous System Diseases, business, Human, Calcification
Abstract

Objective With the identification of mutations in the conserved telomere maintenance component 1 (CTC1) gene as the cause of Coats plus (CP) disease, it has become evident that leukoencephalopathy with calcifications and cysts (LCC) is a distinct genetic entity. Patients and Methods A total of 15 patients with LCC were identified from our database of patients with intracranial calcification. The clinical and radiological features are described. Results The median age (range) at presentation was 10 months (range, 2 days-54 years). Of the 15 patients, 9 presented with epileptic seizures, 5 with motor abnormalities, and 1 with developmental delay. Motor abnormalities developed in 14 patients and cognitive problems in 13 patients. Dense calcification occurred in the basal ganglia, thalami, dentate nucleus, brain stem, deep gyri, deep white matter, and in a pericystic distribution. Diffuse leukoencephalopathy was present in all patients, and it was usually symmetrical involving periventricular, deep, and sometimes subcortical, regions. Cysts developed in the basal ganglia, thalamus, deep white matter, cerebellum, or brain stem. In unaffected areas, normal myelination was present. No patient demonstrated cerebral atrophy. Conclusion LCC shares the neuroradiological features of CP. However, LCC is a purely neurological disorder distinguished genetically by the absence of mutations in CTC1. The molecular cause(s) of LCC has (have) not yet been determined. ispartof: Neuropediatrics vol:45 issue:3 pages:175-82 ispartof: location:Germany status: published

Published
2014

39. From observations to trials: the ketogenic diet and epilepsy

Author

Wiznitzer, Max, Neal, Elizabeth G, Chaffe, Hannah, Schwartz, Ruby H, Lawson, Margaret S, Edwards, Nicole, Fitzsimmons, Geogianna, Whitney, Andrea, and Cross, J Helen

Subjects
*EPILEPSY prevention, *AGE distribution, *BRAIN, *COMPARATIVE studies, *ELEMENTAL diet, *EPILEPSY, *GENETIC disorders, *KETOGENIC diet, *KETONES, *LIPID metabolism disorders, *RESEARCH methodology, *MEDICAL cooperation, *PATIENT compliance, *RESEARCH, *STATISTICS, *DATA analysis, *EVALUATION research, *RANDOMIZED controlled trials, *TREATMENT effectiveness, *CHILDREN, BRAIN metabolism
Abstract

Background: The ketogenic diet has been widely and successfully used to treat children with drug-resistant epilepsy since the 1920s. The aim of this study was to test the efficacy of the ketogenic diet in a randomised controlled trial.Methods: 145 children aged between 2 and 16 years who had at least daily seizures (or more than seven seizures per week), had failed to respond to at least two antiepileptic drugs, and had not been treated previously with the ketogenic diet participated in a randomised controlled trial of its efficacy to control seizures. Enrolment for the trial ran between December, 2001, and July, 2006. Children were seen at one of two hospital centres or a residential centre for young people with epilepsy. Children were randomly assigned to receive a ketogenic diet, either immediately or after a 3-month delay, with no other changes to treatment (control group). Neither the family nor investigators were blinded to the group assignment. Early withdrawals were recorded, and seizure frequency on the diet was assessed after 3 months and compared with that of the controls. The primary endpoint was a reduction in seizures; analysis was intention to treat. Tolerability of the diet was assessed by questionnaire at 3 months. The trial is registered with ClinicalTrials.gov, number NCT00564915.Findings: 73 children were assigned to the ketogenic diet and 72 children to the control group. Data from 103 children were available for analysis: 54 on the ketogenic diet and 49 controls. Of those who did not complete the trial, 16 children did not receive their intervention, 16 did not provide adequate data, and ten withdrew from the treatment before the 3-month review, six because of intolerance. After 3 months, the mean percentage of baseline seizures was significantly lower in the diet group than in the controls (62.0%vs 136.9%, 75% decrease, 95% CI 42.4-107.4%; p<0.0001). 28 children (38%) in the diet group had greater than 50% seizure reduction compared with four (6%) controls (p<0.0001), and five children (7%) in the diet group had greater than 90% seizure reduction compared with no controls (p=0.0582). There was no significant difference in the efficacy of the treatment between symptomatic generalised or symptomatic focal syndromes. The most frequent side-effects reported at 3-month review were constipation, vomiting, lack of energy, and hunger.Interpretation: The results from this trial of the ketogenic diet support its use in children with treatment-intractable epilepsy.Funding: HSA Charitable Trust; Smiths Charity; Scientific Hospital Supplies; Milk Development Council. [ABSTRACT FROM AUTHOR]

Published
2008
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40. ATP6V0C variants impair V-ATPase function causing a neurodevelopmental disorder often associated with epilepsy.

Author

Mattison KA, Tossing G, Mulroe F, Simmons C, Butler KM, Schreiber A, Alsadah A, Neilson DE, Naess K, Wedell A, Wredenberg A, Sorlin A, McCann E, Burghel GJ, Menendez B, Hoganson GE, Botto LD, Filloux FM, Aledo-Serrano Á, Gil-Nagel A, Tatton-Brown K, Verbeek NE, van der Zwaag B, Aleck KA, Fazenbaker AC, Balciuniene J, Dubbs HA, Marsh ED, Garber K, Ek J, Duno M, Hoei-Hansen CE, Deardorff MA, Raca G, Quindipan C, van Hirtum-Das M, Breckpot J, Hammer TB, Møller RS, Whitney A, Douglas AGL, Kharbanda M, Brunetti-Pierri N, Morleo M, Nigro V, May HJ, Tao JX, Argilli E, Sherr EH, Dobyns WB, Baines RA, Warwicker J, Parker JA, Banka S, Campeau PM, and Escayg A

Subjects
Humans, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism, Adenosine Triphosphate, Vacuolar Proton-Translocating ATPases genetics, Vacuolar Proton-Translocating ATPases metabolism, Epilepsy genetics
Abstract

The vacuolar H+-ATPase is an enzymatic complex that functions in an ATP-dependent manner to pump protons across membranes and acidify organelles, thereby creating the proton/pH gradient required for membrane trafficking by several different types of transporters. We describe heterozygous point variants in ATP6V0C, encoding the c-subunit in the membrane bound integral domain of the vacuolar H+-ATPase, in 27 patients with neurodevelopmental abnormalities with or without epilepsy. Corpus callosum hypoplasia and cardiac abnormalities were also present in some patients. In silico modelling suggested that the patient variants interfere with the interactions between the ATP6V0C and ATP6V0A subunits during ATP hydrolysis. Consistent with decreased vacuolar H+-ATPase activity, functional analyses conducted in Saccharomyces cerevisiae revealed reduced LysoSensor fluorescence and reduced growth in media containing varying concentrations of CaCl2. Knockdown of ATP6V0C in Drosophila resulted in increased duration of seizure-like behaviour, and the expression of selected patient variants in Caenorhabditis elegans led to reduced growth, motor dysfunction and reduced lifespan. In summary, this study establishes ATP6V0C as an important disease gene, describes the clinical features of the associated neurodevelopmental disorder and provides insight into disease mechanisms., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2023
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41. Leukoencephalopathy with calcifications and cysts: Genetic and phenotypic spectrum.

Author

Crow YJ, Marshall H, Rice GI, Seabra L, Jenkinson EM, Baranano K, Battini R, Berger A, Blair E, Blauwblomme T, Bolduc F, Boddaert N, Buckard J, Burnett H, Calvert S, Caumes R, Ng AC, Chiang D, Clifford DB, Cordelli DM, de Burca A, Demic N, Desguerre I, De Waele L, Di Fonzo A, Dunham SR, Dyack S, Elmslie F, Ferrand M, Fisher G, Karimiani EG, Ghoumid J, Gibbon F, Goel H, Hilmarsen HT, Hughes I, Jacob A, Jones EA, Kumar R, Leventer RJ, MacDonald S, Maroofian R, Mehta SG, Metz I, Monfrini E, Neumann D, Noetzel M, O'Driscoll M, Õunap K, Panzer A, Parikh S, Prabhakar P, Ramond F, Sandford R, Saneto R, Soh C, Stutterd CA, Subramanian GM, Talbot K, Thomas RH, Toro C, Touraine R, Wakeling E, Wassmer E, Whitney A, Livingston JH, O'Keefe RT, and Badrock AP

Subjects
Adolescent, Adult, Aged, Animals, Calcinosis complications, Calcinosis pathology, Child, Child, Preschool, Consanguinity, Disease Models, Animal, Female, Heterozygote, Humans, Infant, Infant, Newborn, Leukoencephalopathies complications, Leukoencephalopathies pathology, Male, Middle Aged, Pathology, Molecular, Young Adult, Zebrafish genetics, Calcinosis genetics, Genetic Association Studies, Leukoencephalopathies genetics, RNA, Small Nucleolar genetics
Abstract

Biallelic mutations in SNORD118, encoding the small nucleolar RNA U8, cause leukoencephalopathy with calcifications and cysts (LCC). Given the difficulty in interpreting the functional consequences of variants in nonprotein encoding genes, and the high allelic polymorphism across SNORD118 in controls, we set out to provide a description of the molecular pathology and clinical spectrum observed in a cohort of patients with LCC. We identified 64 affected individuals from 56 families. Age at presentation varied from 3 weeks to 67 years, with disease onset after age 40 years in eight patients. Ten patients had died. We recorded 44 distinct, likely pathogenic, variants in SNORD118. Fifty two of 56 probands were compound heterozygotes, with parental consanguinity reported in only three families. Forty nine of 56 probands were either heterozygous (46) or homozygous (three) for a mutation involving one of seven nucleotides that facilitate a novel intramolecular interaction between the 5' end and 3' extension of precursor-U8. There was no obvious genotype-phenotype correlation to explain the marked variability in age at onset. Complementing recently published functional analyses in a zebrafish model, these data suggest that LCC most often occurs due to combinatorial severe and milder mutations, with the latter mostly affecting 3' end processing of precursor-U8., (© 2020 Wiley Periodicals LLC.)

Published
2021
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