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51. Erratum to: Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data (Scientific Reports, (2018), 8, 1, (1300), 10.1038/s41598-017-14403-y)

Author

Farmery, James H. R., Smith, Mike L., Huissoon, Aarnoud, Furnell, Abigail, Mead, Adam, Levine, Adam P., Manzur, Adnan, Thrasher, Adrian, Greenhalgh, Alan, Parker, Alasdair, Sanchis-Juan, Alba, Richter, Alex, Gardham, Alice, Lawrie, Allan, Sohal, Aman, Creaser-Myers, Amanda, Frary, Amy, Greinacher, Andreas, Themistocleous, Andreas, Peacock, Andrew J., Marshall, Andrew, Mumford, Andrew, Rice, Andrew, Webster, Andrew, Brady, Angie, Koziell, Ania, Manson, Ania, Chandra, Anita, Hensiek, Anke, Veld, Anna Huis in’t, Maw, Anna, Kelly, Anne M., Moore, Anthony, Vonk Noordegraaf, Anton, Attwood, Antony, Herwadkar, Archana, Ghofrani, Ardi, Houweling, Arjan C., Girerd, Barbara, Furie, Bruce, Treacy, Carmen M., Millar, Carolyn M., Sewell, Carrock, Roughley, Catherine, Titterton, Catherine, Williamson, Catherine, Hadinnapola, Charaka, Deshpande, Charu, Toh, Cheng-Hock, Bacchelli, Chiara, Patch, Chris, Geet, Chris Van, Babbs, Christian, Bryson, Christine, Penkett, Christopher J., Rhodes, Christopher J., Watt, Christopher, Bethune, Claire, Booth, Claire, Lentaigne, Claire, Mcjannet, Coleen, Church, Colin, French, Courtney, Samarghitean, Crina, Halmagyi, Csaba, Gale, Daniel, Greene, Daniel, Hart, Daniel, Allsup, David, Bennett, David, Edgar, David, Kiely, David G., Gosal, David, Perry, David J., Keeling, David, Montani, David, Shipley, Debbie, Whitehorn, Deborah, Fletcher, Debra, Krishnakumar, Deepa, Grozeva, Detelina, Kumararatne, Dinakantha, Thompson, Dorothy, Josifova, Dragana, Maher, Eamonn, Wong, Edwin K. S., Murphy, Elaine, Dewhurst, Eleanor, Louka, Eleni, Rosser, Elisabeth, Chalmers, Elizabeth, Colby, Elizabeth, Drewe, Elizabeth, Mcdermott, Elizabeth, Thomas, Ellen, Staples, Emily, Clement, Emma, Matthews, Emma, Wakeling, Emma, Oksenhendler, Eric, Turro, Ernest, Reid, Evan, Wassmer, Evangeline, Raymond, F. Lucy, Fengyuan, Hu, Kennedy, Fiona, Soubrier, Florent, Flinter, Frances, Kovacs, Gabor, Polwarth, Gary, Ambegaonkar, Gautum, Arno, Gavin, Hudson, Gavin, Woods, Geoff, Coghlan, Gerry, Hayman, Grant, Arumugakani, Gururaj, Schotte, Gwen, Cook, H. Terry, Alachkar, Hana, Lango Allen, Hana, Lango-Allen, Hana, Stark, Hannah, Stauss, Hans, Schulze, Harald, Boggard, Harm J., Baxendale, Helen, Dolling, Helen, Firth, Helen, Gall, Henning, Watson, Henry, Longhurst, Hilary, Markus, Hugh S., Watkins, Hugh, Simeoni, Ilenia, Emmerson, Ingrid, Roberts, Irene, Quinti, Isabella, Wanjiku, Ivy, Gibbs, J. Simon R., Thaventhiran, James, Whitworth, James, Hurst, Jane, Collins, Janine, Suntharalingam, Jay, Payne, Jeanette, Thachil, Jecko, Martin, Jennifer M., Martin, Jennifer, Carmichael, Jenny, Maimaris, Jesmeen, Paterson, Joan, Pepke-Zaba, Joanna, Heemskerk, Johan W. M., Gebhart, Johanna, Davis, John, Pasi, John, Bradley, John R., Wharton, John, Stephens, Jonathan, Rankin, Julia, Anderson, Julie, Vogt, Julie, von Ziegenweldt, Julie, Rehnstrom, Karola, Megy, Karyn, Talks, Kate, Peerlinck, Kathelijne, Yates, Katherine, Freson, Kathleen, Stirrups, Kathleen, Gomez, Keith, Smith, Kenneth G. C., Carss, Keren, Rue-Albrecht, Kevin, Gilmour, Kimberley, Masati, Larahmie, Scelsi, Laura, Southgate, Laura, Ranganathan, Lavanya, Ginsberg, Lionel, Devlin, Lisa, Willcocks, Lisa, Ormondroyd, Liz, Lorenzo, Lorena, Harper, Lorraine, Allen, Louise, Daugherty, Louise, Chitre, Manali, Kurian, Manju, Humbert, Marc, Tischkowitz, Marc, Bitner-Glindzicz, Maria, Erwood, Marie, Scully, Marie, Veltman, Marijke, Caulfield, Mark, Layton, Mark, Mccarthy, Mark, Ponsford, Mark, Toshner, Mark, Bleda, Marta, Wilkins, Martin, Mathias, Mary, Reilly, Mary, Afzal, Maryam, Brown, Matthew, Rondina, Matthew, Stubbs, Matthew, Haimel, Matthias, Lees, Melissa, Laffan, Michael A., Browning, Michael, Gattens, Michael, Richards, Michael, Michaelides, Michel, Lambert, Michele P., Makris, Mike, De Vries, Minka, Mahdi-Rogers, Mohamed, Saleem, Moin, Thomas, Moira, Holder, Muriel, Eyries, Mélanie, Clements-Brod, Naomi, Canham, Natalie, Dormand, Natalie, Zuydam, Natalie Van, Kingston, Nathalie, Ghali, Neeti, Cooper, Nichola, Morrell, Nicholas W., Yeatman, Nigel, Roy, Noémi, Shamardina, Olga, Alavijeh, Omid S., Gresele, Paolo, Nurden, Paquita, Chinnery, Patrick, Deegan, Patrick, Yong, Patrick, Yu-Wai-Man, Patrick, Corris, Paul A., Calleja, Paul, Gissen, Paul, Bolton-Maggs, Paula, Rayner-Matthews, Paula, Ghataorhe, Pavandeep K., Gordins, Pavel, Stein, Penelope, Collins, Peter, Dixon, Peter, Kelleher, Peter, Ancliff, Phil, Ping, Yu, Tait, R. Campbell, Linger, Rachel, Doffinger, Rainer, Machado, Rajiv, Kazmi, Rashid, Sargur, Ravishankar, Favier, Remi, Tan, Rhea, Liesner, Ri, Antrobus, Richard, Sandford, Richard, Scott, Richard, Trembath, Richard, Horvath, Rita, Hadden, Rob, Mackenzieross, Rob V., Henderson, Robert, Maclaren, Robert, James, Roger, Ghurye, Rohit, Dacosta, Rosa, Hague, Rosie, Mapeta, Rutendo, Armstrong, Ruth, Noorani, Sadia, Murng, Sai, Santra, Saikat, Tuna, Salih, Johnson, Sally, Chong, Sam, Lear, Sara, Walker, Sara, Goddard, Sarah, Mangles, Sarah, Westbury, Sarah, Mehta, Sarju, Hackett, Scott, Nejentsev, Sergey, Moledina, Shahin, Bibi, Shahnaz, Meehan, Sharon, Othman, Shokri, Revel-Vilk, Shoshana, Holden, Simon, Mcgowan, Simon, Staines, Simon, Savic, Sinisa, Burns, Siobhan, Grigoriadou, Sofia, Papadia, Sofia, Ashford, Sofie, Schulman, Sol, Ali, Sonia, Park, Soo-Mi, Davies, Sophie, Stock, Sophie, Ali, Souad, Deevi, Sri V. V., Gräf, Stefan, Ghio, Stefano, Wort, Stephen J., Jolles, Stephen, Austin, Steve, Welch, Steve, Meacham, Stuart, Rankin, Stuart, Walker, Suellen, Seneviratne, Suranjith, Holder, Susan, Sivapalaratnam, Suthesh, Richardson, Sylvia, Kuijpers, Taco, Kuijpers, Taco W., Bariana, Tadbir K., Bakchoul, Tamam, Everington, Tamara, Renton, Tara, Young, Tim, Aitman, Timothy, Warner, Timothy Q., Vale, Tom, Hammerton, Tracey, Pollock, Val, Matser, Vera, Cookson, Victoria, Clowes, Virginia, Qasim, Waseem, Wei, Wei, Erber, Wendy N., Ouwehand, Willem H., Astle, William, Egner, William, Turek, Wojciech, Henskens, Yvonne, Tan, Yvonne, and Lynch, Andy G.

Subjects
Multidisciplinary
Published
2018

52. Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data

Author

Farmery, James H. R., Smith, Mike L., Huissoon, Aarnoud, Furnell, Abigail, Mead, Adam, Levine, Adam P., Manzur, Adnan, Thrasher, Adrian, Greenhalgh, Alan, Parker, Alasdair, Sanchis-Juan, Alba, Richter, Alex, Gardham, Alice, Lawrie, Allan, Sohal, Aman, Creaser-Myers, Amanda, Frary, Amy, Greinacher, Andreas, Themistocleous, Andreas, Peacock, Andrew J., Marshall, Andrew, Mumford, Andrew, Rice, Andrew, Webster, Andrew, Brady, Angie, Koziell, Ania, Manson, Ania, Chandra, Anita, Hensiek, Anke, Veld, Anna Huis In'T., Maw, Anna, Kelly, Anne M., Moore, Anthony, Vonk Noordegraaf, Anton, Attwood, Antony, Herwadkar, Archana, Ghofrani, Ardi, Houweling, Arjan C., Girerd, Barbara, Furie, Bruce, Treacy, Carmen M., Millar, Carolyn M., Sewell, Carrock, Roughley, Catherine, Titterton, Catherine, Williamson, Catherine, Hadinnapola, Charaka, Deshpande, Charu, Toh, Cheng-Hock, Bacchelli, Chiara, Patch, Chris, Geet, Chris Van, Babbs, Christian, Bryson, Christine, Penkett, Christopher J., Rhodes, Christopher J., Watt, Christopher, Bethune, Claire, Booth, Claire, Lentaigne, Claire, McJannet, Coleen, Church, Colin, French, Courtney, Samarghitean, Crina, Halmagyi, Csaba, Gale, Daniel, Greene, Daniel, Hart, Daniel, Allsup, David, Bennett, David, Edgar, David, Kiely, David G., Gosal, David, Perry, David J., Keeling, David, Montani, David, Shipley, Debbie, Whitehorn, Deborah, Fletcher, Debra, Krishnakumar, Deepa, Grozeva, Detelina, Kumararatne, Dinakantha, Thompson, Dorothy, Josifova, Dragana, Maher, Eamonn, Wong, Edwin K. S., Murphy, Elaine, Dewhurst, Eleanor, Louka, Eleni, Rosser, Elisabeth, Chalmers, Elizabeth, Colby, Elizabeth, Drewe, Elizabeth, McDermott, Elizabeth, Thomas, Ellen, Staples, Emily, Clement, Emma, Matthews, Emma, Wakeling, Emma, Oksenhendler, Eric, Turro, Ernest, Reid, Evan, Wassmer, Evangeline, Raymond, F. Lucy, Hu, Fengyuan, Kennedy, Fiona, Soubrier, Florent, Flinter, Frances, Kovacs, Gabor, Polwarth, Gary, Ambegaonkar, Gautum, Arno, Gavin, Hudson, Gavin, Woods, Geoff, Coghlan, Gerry, Hayman, Grant, Arumugakani, Gururaj, Schotte, Gwen, Cook, H. Terry, Alachkar, Hana, Lango Allen, Hana, Lango-Allen, Hana, Stark, Hannah, Stauss, Hans, Schulze, Harald, Boggard, Harm J., Baxendale, Helen, Dolling, Helen, Firth, Helen, Gall, Henning, Watson, Henry, Longhurst, Hilary, Markus, Hugh S., Watkins, Hugh, Simeoni, Ilenia, Emmerson, Ingrid, Roberts, Irene, Quinti, Isabella, Wanjiku, Ivy, Gibbs, J. Simon R., Thaventhiran, James, Whitworth, James, Hurst, Jane, Collins, Janine, Suntharalingam, Jay, Payne, Jeanette, Thachil, Jecko, Martin, Jennifer M., Carmichael, Jenny, Maimaris, Jesmeen, Paterson, Joan, Pepke-Zaba, Joanna, Heemskerk, Johan W. M., Gebhart, Johanna, Davis, John, Pasi, John, Bradley, John R., Wharton, John, Stephens, Jonathan, Rankin, Julia, Anderson, Julie, Vogt, Julie, von Ziegenweldt, Julie, Rehnstrom, Karola, Megy, Karyn, Talks, Kate, Peerlinck, Kathelijne, Yates, Katherine, Freson, Kathleen, Stirrups, Kathleen, Gomez, Keith, Smith, Kenneth G. C., Rue-Albrecht, Kevin, Gilmour, Kimberley, Masati, Larahmie, Scelsi, Laura, Southgate, Laura, Ranganathan, Lavanya, Ginsberg, Lionel, Devlin, Lisa, Willcocks, Lisa, Ormondroyd, Liz, Lorenzo, Lorena, Harper, Lorraine, Allen, Louise, Daugherty, Louise, Chitre, Manali, Kurian, Manju, Humbert, Marc, Tischkowitz, Marc, Bitner-Glindzicz, Maria, Erwood, Marie, Scully, Marie, Veltman, Marijke, Caulfield, Mark, Layton, Mark, McCarthy, Mark, Ponsford, Mark, Toshner, Mark, Bleda, Marta, Wilkins, Martin, Mathias, Mary, Reilly, Mary, Afzal, Maryam, Brown, Matthew, Rondina, Matthew, Stubbs, Matthew, Haimel, Matthias, Lees, Melissa, Laffan, Michael A., Browning, Michael, Gattens, Michael, Richards, Michael, Michaelides, Michel, Lambert, Michele P., Makris, Mike, de Vries, Minka, Mahdi-Rogers, Mohamed, Saleem, Moin, Thomas, Moira, Holder, Muriel, Eyries, M. lanie, Clements-Brod, Naomi, Canham, Natalie, Dormand, Natalie, Zuydam, Natalie Van, Kingston, Nathalie, Ghali, Neeti, Cooper, Nichola, Morrell, Nicholas W., Yeatman, Nigel, Roy, Noémi, Shamardina, Olga, Alavijeh, Omid S., Gresele, Paolo, Nurden, Paquita, Chinnery, Patrick, Deegan, Patrick, Yong, Patrick, Man, Patrick Yu Wai, Corris, Paul A., Calleja, Paul, Gissen, Paul, Bolton-Maggs, Paula, Rayner-Matthews, Paula, Ghataorhe, Pavandeep K., Gordins, Pavel, Stein, Penelope, Collins, Peter, Dixon, Peter, Kelleher, Peter, Ancliff, Phil, Yu, Ping, Tait, R. Campbell, Linger, Rachel, Doffinger, Rainer, Machado, Rajiv, Kazmi, Rashid, Sargur, Ravishankar, Favier, Remi, Tan, Rhea, Liesner, Ri, Antrobus, Richard, Sandford, Richard, Scott, Richard, Trembath, Richard, Horvath, Rita, Hadden, Rob, Mackenzieross, Rob V., Henderson, Robert, MacLaren, Robert, James, Roger, Ghurye, Rohit, Dacosta, Rosa, Hague, Rosie, Mapeta, Rutendo, Armstrong, Ruth, Noorani, Sadia, Murng, Sai, Santra, Saikat, Tuna, Salih, Johnson, Sally, Chong, Sam, Lear, Sara, Walker, Sara, Goddard, Sarah, Mangles, Sarah, Westbury, Sarah, Mehta, Sarju, Hackett, Scott, Nejentsev, Sergey, Moledina, Shahin, Bibi, Shahnaz, Meehan, Sharon, Othman, Shokri, Revel-Vilk, Shoshana, Holden, Simon, McGowan, Simon, Staines, Simon, Savic, Sinisa, Burns, Siobhan, Grigoriadou, Sofia, Papadia, Sofia, Ashford, Sofie, Schulman, Sol, Ali, Sonia, Park, Soo-Mi, Davies, Sophie, Stock, Sophie, Ali, Souad, Deevi, Sri V. V., Gräf, Stefan, Ghio, Stefano, Wort, Stephen J., Jolles, Stephen, Austin, Steve, Welch, Steve, Meacham, Stuart, Rankin, Stuart, Walker, Suellen, Seneviratne, Suranjith, Holder, Susan, Sivapalaratnam, Suthesh, Richardson, Sylvia, Kuijpers, Taco, Kuijpers, Taco W., Bariana, Tadbir K., Bakchoul, Tamam, Everington, Tamara, Renton, Tara, Young, Tim, Aitman, Timothy, Warner, Timothy Q., Vale, Tom, Hammerton, Tracey, Pollock, Val, Matser, Vera, Cookson, Victoria, Clowes, Virginia, Qasim, Waseem, Wei, Wei, Erber, Wendy N., Ouwehand, Willem H., Astle, William, Egner, William, Turek, Wojciech, Henskens, Yvonne, Tan, Yvonne, Lynch, Andy G., Other departments, ARD - Amsterdam Reproduction and Development, Paediatric Infectious Diseases / Rheumatology / Immunology, Peerlinck, Kathelijne, Freson, Kathleen, University of St Andrews. Statistics, University of St Andrews. School of Medicine, University of St Andrews. Population and Behavioural Science Division, University of St Andrews. Cellular Medicine Division, Rue-Albrecht, K, VU University medical center, ACS - Pulmonary hypertension & thrombosis, Pulmonary medicine, APH - Quality of Care, Amsterdam Reproduction & Development (AR&D), Human genetics, ACS - Atherosclerosis & ischemic syndromes, Molecular cell biology and Immunology, Pediatric surgery, APH - Aging & Later Life, Lynch, Andy G [0000-0002-7876-7338], and Apollo - University of Cambridge Repository

Subjects
Telomerase, Carcinoma, Hepatocellular, Genotype, Science, QH301 Biology, Induced Pluripotent Stem Cells, Primary Cell Culture, Sequencing data, Gene Expression, Computational biology, Biology, Article, RC0254, 03 medical and health sciences, QH301, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Humans, 030304 developmental biology, Whole genome sequencing, 0303 health sciences, Ploidies, Multidisciplinary, Whole Genome Sequencing, Telomere biology, RC0254 Neoplasms. Tumors. Oncology (including Cancer), Liver Neoplasms, Telomere Homeostasis, Mesenchymal Stem Cells, DAS, Telomere, Publisher Correction, T Technology, Cancer data, 030220 oncology & carcinogenesis, Medicine, Ploidy, Algorithms
Abstract

Funding: Cancer Research UK Programme Grant to Simon Tavaré (C14303/A17197) (JHRF, AGL, MLS); European Commission through the Horizon 2020 project SOUND (Grant Agreement no. 633974) (AGL). Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype. Publisher PDF

Published
2018
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53. Sphingolipid dysregulation due to lack of functional KDSR impairs proplatelet formation causing thrombocytopenia

Author

Bariana, Tadbir K., primary, Labarque, Veerle, additional, Heremans, Jessica, additional, Thys, Chantal, additional, De Reys, Mara, additional, Greene, Daniel, additional, Jenkins, Benjamin, additional, Grassi, Luigi, additional, Seyres, Denis, additional, Burden, Frances, additional, Whitehorn, Deborah, additional, Shamardina, Olga, additional, Papadia, Sofia, additional, Gomez, Keith, additional, BioResource, NIHR, additional, Van Geet, Chris, additional, Koulman, Albert, additional, Ouwehand, Willem H., additional, Ghevaert, Cedric, additional, Frontini, Mattia, additional, Turro, Ernest, additional, and Freson, Kathleen, additional

Published
2018
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54. Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans

Author

Tuijnenburg, Paul, primary, Lango Allen, Hana, additional, Burns, Siobhan O., additional, Greene, Daniel, additional, Jansen, Machiel H., additional, Staples, Emily, additional, Stephens, Jonathan, additional, Carss, Keren J., additional, Biasci, Daniele, additional, Baxendale, Helen, additional, Thomas, Moira, additional, Chandra, Anita, additional, Kiani-Alikhan, Sorena, additional, Longhurst, Hilary J., additional, Seneviratne, Suranjith L., additional, Oksenhendler, Eric, additional, Simeoni, Ilenia, additional, de Bree, Godelieve J., additional, Tool, Anton T.J., additional, van Leeuwen, Ester M.M., additional, Ebberink, Eduard H.T.M., additional, Meijer, Alexander B., additional, Tuna, Salih, additional, Whitehorn, Deborah, additional, Brown, Matthew, additional, Turro, Ernest, additional, Thrasher, Adrian J., additional, Smith, Kenneth G.C., additional, Thaventhiran, James E., additional, Kuijpers, Taco W., additional, Adhya, Zoe, additional, Alachkar, Hana, additional, Anantharachagan, Ariharan, additional, Antrobus, Richard, additional, Arumugakani, Gururaj, additional, Bacchelli, Chiara, additional, Bethune, Claire, additional, Bibi, Shahnaz, additional, Boardman, Barbara, additional, Booth, Claire, additional, Browning, Michael, additional, Brownlie, Mary, additional, Burns, Siobhan, additional, Clifford, Hayley, additional, Cooper, Nichola, additional, Davies, Sophie, additional, Dempster, John, additional, Devlin, Lisa, additional, Doffinger, Rainer, additional, Drewe, Elizabeth, additional, Edgar, David, additional, Egner, William, additional, El-Shanawany, Tariq, additional, Gaspar, Bobby, additional, Ghurye, Rohit, additional, Gilmour, Kimberley, additional, Goddard, Sarah, additional, Gordins, Pavel, additional, Grigoriadou, Sofia, additional, Hackett, Scott, additional, Hague, Rosie, additional, Harper, Lorraine, additional, Hayman, Grant, additional, Herwadkar, Archana, additional, Hughes, Stephen, additional, Huissoon, Aarnoud, additional, Jolles, Stephen, additional, Jones, Julie, additional, Kelleher, Peter, additional, Klein, Nigel, additional, Kuijpers, Taco, additional, Kumararatne, Dinakantha, additional, Laffan, James, additional, Lear, Sara, additional, Longhurst, Hilary, additional, Lorenzo, Lorena, additional, Maimaris, Jesmeen, additional, Manson, Ania, additional, McDermott, Elizabeth, additional, Millar, Hazel, additional, Mistry, Anoop, additional, Morrisson, Valerie, additional, Murng, Sai, additional, Nasir, Iman, additional, Nejentsev, Sergey, additional, Noorani, Sadia, additional, Ponsford, Mark, additional, Qasim, Waseem, additional, Quinn, Ellen, additional, Quinti, Isabella, additional, Richter, Alex, additional, Samarghitean, Crina, additional, Sargur, Ravishankar, additional, Savic, Sinisa, additional, Seneviratne, Suranjith, additional, Sewall, Carrock, additional, Shackley, Fiona, additional, Stauss, Hans, additional, Steele, Cathal, additional, Thaventhiran, James, additional, Thrasher, Adrian, additional, Welch, Steve, additional, Willcocks, Lisa, additional, Workman, Sarita, additional, Worth, Austen, additional, Yeatman, Nigel, additional, Yong, Patrick, additional, Ashford, Sofie, additional, Bradley, John, additional, Fletcher, Debra, additional, Hammerton, Tracey, additional, James, Roger, additional, Kingston, Nathalie, additional, Ouwehand, Willem, additional, Penkett, Christopher, additional, Raymond, F Lucy, additional, Stirrups, Kathleen, additional, Veltman, Marijke, additional, Young, Tim, additional, Clements-Brod, Naomi, additional, Davis, John, additional, Dewhurst, Eleanor, additional, Erwood, Marie, additional, Frary, Amy, additional, Linger, Rachel, additional, Martin, Jennifer, additional, Papadia, Sofia, additional, Rehnstrom, Karola, additional, Astle, William, additional, Attwood, Antony, additional, Bleda, Marta, additional, Carss, Keren, additional, Daugherty, Louise, additional, Deevi, Sri, additional, Graf, Stefan, additional, Halmagyi, Csaba, additional, Haimel, Matthias, additional, Hu, Fengyuan, additional, Matser, Vera, additional, Meacham, Stuart, additional, Megy, Karyn, additional, Shamardina, Olga, additional, Titterton, Catherine, additional, Yu, Ping, additional, von Ziegenweldt, Julie, additional, Furnell, Abigail, additional, Mapeta, Rutendo, additional, Staines, Simon, additional, Rayner-Matthews, Paula, additional, and Watt, Christopher, additional

Published
2018
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55. De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures

Author

Ito, Yoko, primary, Carss, Keren J., additional, Duarte, Sofia T., additional, Hartley, Taila, additional, Keren, Boris, additional, Kurian, Manju A., additional, Marey, Isabelle, additional, Charles, Perinne, additional, Mendonça, Carla, additional, Nava, Caroline, additional, Pfundt, Rolph, additional, Sanchis-Juan, Alba, additional, van Bokhoven, Hans, additional, van Essen, Anthony, additional, van Ravenswaaij-Arts, Conny, additional, Boycott, Kym M., additional, Kernohan, Kristin D., additional, Dyack, Sarah, additional, Raymond, F. Lucy, additional, Aitman, Timothy, additional, Bennett, David, additional, Caulfield, Mark, additional, Chinnery, Patrick, additional, Gale, Daniel, additional, Koziell, Ania, additional, Kuijpers, Taco W., additional, Laffan, Michael A., additional, Maher, Eamonn, additional, Markus, Hugh S., additional, Morrell, Nicholas W., additional, Ouwehand, Willem H., additional, Perry, David J., additional, Roberts, Irene, additional, Smith, Kenneth G.C., additional, Thrasher, Adrian, additional, Watkins, Hugh, additional, Williamson, Catherine, additional, Woods, Geoffrey, additional, Ashford, Sofie, additional, Bradley, John R., additional, Fletcher, Debra, additional, Hammerton, Tracey, additional, James, Roger, additional, Kingston, Nathalie, additional, Penkett, Christopher J., additional, Stirrups, Kathleen, additional, Veltman, Marijke, additional, Young, Tim, additional, Brown, Matthew, additional, Clements-Brod, Naomi, additional, Davis, John, additional, Dewhurst, Eleanor, additional, Dolling, Helen, additional, Erwood, Marie, additional, Frary, Amy, additional, Linger, Rachel, additional, Martin, Jennifer M., additional, Papadia, Sofia, additional, Rehnstrom, Karola, additional, Stark, Hannah, additional, Allsup, David, additional, Austin, Steve, additional, Bakchoul, Tamam, additional, Bariana, Tadbir K., additional, Bolton-Maggs, Paula, additional, Chalmers, Elizabeth, additional, Collins, Janine, additional, Collins, Peter, additional, Erber, Wendy N., additional, Everington, Tamara, additional, Favier, Remi, additional, Freson, Kathleen, additional, Furie, Bruce, additional, Gattens, Michael, additional, Gebhart, Johanna, additional, Gomez, Keith, additional, Greene, Daniel, additional, Greinacher, Andreas, additional, Gresele, Paolo, additional, Hart, Daniel, additional, Heemskerk, Johan W.M., additional, Henskens, Yvonne, additional, Kazmi, Rashid, additional, Keeling, David, additional, Kelly, Anne M., additional, Lambert, Michele P., additional, Lentaigne, Claire, additional, Liesner, Ri, additional, Makris, Mike, additional, Mangles, Sarah, additional, Mathias, Mary, additional, Millar, Carolyn M., additional, Mumford, Andrew, additional, Nurden, Paquita, additional, Payne, Jeanette, additional, Pasi, John, additional, Peerlinck, Kathelijne, additional, Revel-Vilk, Shoshana, additional, Richards, Michael, additional, Rondina, Matthew, additional, Roughley, Catherine, additional, Schulman, Sol, additional, Schulze, Harald, additional, Scully, Marie, additional, Sivapalaratnam, Suthesh, additional, Stubbs, Matthew, additional, Tait, R. Campbell, additional, Talks, Kate, additional, Thachil, Jecko, additional, Toh, Cheng-Hock, additional, Turro, Ernest, additional, Van Geet, Chris, additional, De Vries, Minka, additional, Warner, Timothy Q., additional, Watson, Henry, additional, Westbury, Sarah, additional, Furnell, Abigail, additional, Mapeta, Rutendo, additional, Rayner-Matthews, Paula, additional, Simeoni, Ilenia, additional, Staines, Simon, additional, Stephens, Jonathan, additional, Watt, Christopher, additional, Whitehorn, Deborah, additional, Attwood, Antony, additional, Daugherty, Louise, additional, Deevi, Sri V.V., additional, Halmagyi, Csaba, additional, Hu, Fengyuan, additional, Matser, Vera, additional, Meacham, Stuart, additional, Megy, Karyn, additional, Shamardina, Olga, additional, Titterton, Catherine, additional, Tuna, Salih, additional, Yu, Ping, additional, von Ziegenweldt, Julie, additional, Astle, William, additional, Bleda, Marta, additional, Gräf, Stefan, additional, Haimel, Matthias, additional, Lango-Allen, Hana, additional, Richardson, Sylvia, additional, Calleja, Paul, additional, Rankin, Stuart, additional, Turek, Wojciech, additional, Anderson, Julie, additional, Bryson, Christine, additional, Carmichael, Jenny, additional, McJannet, Coleen, additional, Stock, Sophie, additional, Allen, Louise, additional, Ambegaonkar, Gautum, additional, Armstrong, Ruth, additional, Arno, Gavin, additional, Bitner-Glindzicz, Maria, additional, Brady, Angie, additional, Canham, Natalie, additional, Chitre, Manali, additional, Clement, Emma, additional, Clowes, Virginia, additional, Deegan, Patrick, additional, Deshpande, Charu, additional, Doffinger, Rainer, additional, Firth, Helen, additional, Flinter, Frances, additional, French, Courtney, additional, Gardham, Alice, additional, Ghali, Neeti, additional, Gissen, Paul, additional, Grozeva, Detelina, additional, Henderson, Robert, additional, Hensiek, Anke, additional, Holden, Simon, additional, Holder, Muriel, additional, Holder, Susan, additional, Hurst, Jane, additional, Josifova, Dragana, additional, Krishnakumar, Deepa, additional, Lees, Melissa, additional, MacLaren, Robert, additional, Maw, Anna, additional, Mehta, Sarju, additional, Michaelides, Michel, additional, Moore, Anthony, additional, Murphy, Elaine, additional, Park, Soo-Mi, additional, Parker, Alasdair, additional, Patch, Chris, additional, Paterson, Joan, additional, Rankin, Julia, additional, Reid, Evan, additional, Rosser, Elisabeth, additional, Sandford, Richard, additional, Santra, Saikat, additional, Scott, Richard, additional, Sohal, Aman, additional, Stein, Penelope, additional, Thomas, Ellen, additional, Thompson, Dorothy, additional, Tischkowitz, Marc, additional, Vogt, Julie, additional, Wakeling, Emma, additional, Wassmer, Evangeline, additional, Webster, Andrew, additional, Ali, Sonia, additional, Ali, Souad, additional, Boggard, Harm J., additional, Church, Colin, additional, Coghlan, Gerry, additional, Cookson, Victoria, additional, Corris, Paul A., additional, Creaser-Myers, Amanda, additional, DaCosta, Rosa, additional, Dormand, Natalie, additional, Eyries, Mélanie, additional, Gall, Henning, additional, Ghataorhe, Pavandeep K., additional, Ghio, Stefano, additional, Ghofrani, Ardi, additional, Gibbs, J. Simon R., additional, Girerd, Barbara, additional, Greenhalgh, Alan, additional, Hadinnapola, Charaka, additional, Houweling, Arjan C., additional, Humbert, Marc, additional, in’t Veld, Anna Huis, additional, Kennedy, Fiona, additional, Kiely, David G., additional, Kovacs, Gabor, additional, Lawrie, Allan, additional, Ross, Rob V. Mackenzie, additional, Machado, Rajiv, additional, Masati, Larahmie, additional, Meehan, Sharon, additional, Moledina, Shahin, additional, Montani, David, additional, Othman, Shokri, additional, Peacock, Andrew J., additional, Pepke-Zaba, Joanna, additional, Pollock, Val, additional, Polwarth, Gary, additional, Ranganathan, Lavanya, additional, Rhodes, Christopher J., additional, Rue-Albrecht, Kevin, additional, Schotte, Gwen, additional, Shipley, Debbie, additional, Soubrier, Florent, additional, Southgate, Laura, additional, Scelsi, Laura, additional, Suntharalingam, Jay, additional, Tan, Yvonne, additional, Toshner, Mark, additional, Treacy, Carmen M., additional, Trembath, Richard, additional, Vonk Noordegraaf, Anton, additional, Walker, Sara, additional, Wanjiku, Ivy, additional, Wharton, John, additional, Wilkins, Martin, additional, Wort, Stephen J., additional, Yates, Katherine, additional, Alachkar, Hana, additional, Antrobus, Richard, additional, Arumugakani, Gururaj, additional, Bacchelli, Chiara, additional, Baxendale, Helen, additional, Bethune, Claire, additional, Bibi, Shahnaz, additional, Booth, Claire, additional, Browning, Michael, additional, Burns, Siobhan, additional, Chandra, Anita, additional, Cooper, Nichola, additional, Davies, Sophie, additional, Devlin, Lisa, additional, Drewe, Elizabeth, additional, Edgar, David, additional, Egner, William, additional, Ghurye, Rohit, additional, Gilmour, Kimberley, additional, Goddard, Sarah, additional, Gordins, Pavel, additional, Grigoriadou, Sofia, additional, Hackett, Scott, additional, Hague, Rosie, additional, Harper, Lorraine, additional, Hayman, Grant, additional, Herwadkar, Archana, additional, Huissoon, Aarnoud, additional, Jolles, Stephen, additional, Kelleher, Peter, additional, Kumararatne, Dinakantha, additional, Lear, Sara, additional, Longhurst, Hilary, additional, Lorenzo, Lorena, additional, Maimaris, Jesmeen, additional, Manson, Ania, additional, McDermott, Elizabeth, additional, Murng, Sai, additional, Nejentsev, Sergey, additional, Noorani, Sadia, additional, Oksenhendler, Eric, additional, Ponsford, Mark, additional, Qasim, Waseem, additional, Quinti, Isabella, additional, Richter, Alex, additional, Samarghitean, Crina, additional, Sargur, Ravishankar, additional, Savic, Sinisa, additional, Seneviratne, Suranjith, additional, Sewell, Carrock, additional, Staples, Emily, additional, Stauss, Hans, additional, Thaventhiran, James, additional, Thomas, Moira, additional, Welch, Steve, additional, Willcocks, Lisa, additional, Yeatman, Nigel, additional, Yong, Patrick, additional, Ancliff, Phil, additional, Babbs, Christian, additional, Layton, Mark, additional, Louka, Eleni, additional, McGowan, Simon, additional, Mead, Adam, additional, Roy, Noémi, additional, Chambers, Jenny, additional, Dixon, Peter, additional, Estiu, Cecelia, additional, Hague, Bill, additional, Marschall, Hanns-Ulrich, additional, Simpson, Michael, additional, Chong, Sam, additional, Emmerson, Ingrid, additional, Ginsberg, Lionel, additional, Gosal, David, additional, Hadden, Rob, additional, Horvath, Rita, additional, Mahdi-Rogers, Mohamed, additional, Manzur, Adnan, additional, Marshall, Andrew, additional, Matthews, Emma, additional, McCarthy, Mark, additional, Reilly, Mary, additional, Renton, Tara, additional, Rice, Andrew, additional, Themistocleous, Andreas, additional, Vale, Tom, additional, Van Zuydam, Natalie, additional, Walker, Suellen, additional, Ormondroyd, Liz, additional, Hudson, Gavin, additional, Wei, Wei, additional, Yu Wai Man, Patrick, additional, Whitworth, James, additional, Afzal, Maryam, additional, Colby, Elizabeth, additional, Saleem, Moin, additional, Alavijeh, Omid S., additional, Cook, H. Terry, additional, Johnson, Sally, additional, Levine, Adam P., additional, Wong, Edwin K.S., additional, Tan, Rhea, additional, MacKenzie, Alex, additional, Majewski, Jacek, additional, Brudno, Michael, additional, Bulman, Dennis, additional, and Dyment, David, additional

Published
2018
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56. Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes

Author

Whitworth, James, primary, Smith, Philip S., additional, Martin, Jose-Ezequiel, additional, West, Hannah, additional, Luchetti, Andrea, additional, Rodger, Faye, additional, Clark, Graeme, additional, Carss, Keren, additional, Stephens, Jonathan, additional, Stirrups, Kathleen, additional, Penkett, Chris, additional, Mapeta, Rutendo, additional, Ashford, Sofie, additional, Megy, Karyn, additional, Shakeel, Hassan, additional, Ahmed, Munaza, additional, Adlard, Julian, additional, Barwell, Julian, additional, Brewer, Carole, additional, Casey, Ruth T., additional, Armstrong, Ruth, additional, Cole, Trevor, additional, Evans, Dafydd Gareth, additional, Fostira, Florentia, additional, Greenhalgh, Lynn, additional, Hanson, Helen, additional, Henderson, Alex, additional, Hoffman, Jonathan, additional, Izatt, Louise, additional, Kumar, Ajith, additional, Kwong, Ava, additional, Lalloo, Fiona, additional, Ong, Kai Ren, additional, Paterson, Joan, additional, Park, Soo-Mi, additional, Chen-Shtoyerman, Rakefet, additional, Searle, Claire, additional, Side, Lucy, additional, Skytte, Anne-Bine, additional, Snape, Katie, additional, Woodward, Emma R., additional, Tischkowitz, Marc D., additional, Maher, Eamonn R., additional, Aitman, Timothy, additional, Alachkar, Hana, additional, Ali, Sonia, additional, Allen, Louise, additional, Allsup, David, additional, Ambegaonkar, Gautum, additional, Anderson, Julie, additional, Antrobus, Richard, additional, Arno, Gavin, additional, Arumugakani, Gururaj, additional, Astle, William, additional, Attwood, Antony, additional, Austin, Steve, additional, Bacchelli, Chiara, additional, Bakchoul, Tamam, additional, Bariana, Tadbir K., additional, Baxendale, Helen, additional, Bennett, David, additional, Bethune, Claire, additional, Bibi, Shahnaz, additional, Bitner-Glindzicz, Maria, additional, Bleda, Marta, additional, Boggard, Harm, additional, Bolton-Maggs, Paula, additional, Booth, Claire, additional, Bradley, John R., additional, Brady, Angie, additional, Brown, Matthew, additional, Browning, Michael, additional, Bryson, Christine, additional, Burns, Siobhan, additional, Calleja, Paul, additional, Canham, Natalie, additional, Carmichael, Jenny, additional, Caulfield, Mark, additional, Chalmers, Elizabeth, additional, Chandra, Anita, additional, Chinnery, Patrick, additional, Chitre, Manali, additional, Church, Colin, additional, Clement, Emma, additional, Clements-Brod, Naomi, additional, Clowes, Virginia, additional, Coghlan, Gerry, additional, Collins, Peter, additional, Cookson, Victoria, additional, Cooper, Nichola, additional, Corris, Paul, additional, Creaser-Myers, Amanda, additional, DaCosta, Rosa, additional, Daugherty, Louise, additional, Davies, Sophie, additional, Davis, John, additional, De Vries, Minka, additional, Deegan, Patrick, additional, Deevi, Sri V.V., additional, Deshpande, Charu, additional, Devlin, Lisa, additional, Dewhurst, Eleanor, additional, Dixon, Peter, additional, Doffinger, Rainer, additional, Dormand, Natalie, additional, Drewe, Elizabeth, additional, Edgar, David, additional, Egner, William, additional, Erber, Wendy N., additional, Erwood, Marie, additional, Everington, Tamara, additional, Favier, Remi, additional, Firth, Helen, additional, Fletcher, Debra, additional, Flinter, Frances, additional, Frary, Amy, additional, Freson, Kathleen, additional, Furie, Bruce, additional, Furnell, Abigail, additional, Gale, Daniel, additional, Gardham, Alice, additional, Gattens, Michael, additional, Ghali, Neeti, additional, Ghataorhe, Pavandeep K., additional, Ghurye, Rohit, additional, Gibbs, Simon, additional, Gilmour, Kimberley, additional, Gissen, Paul, additional, Goddard, Sarah, additional, Gomez, Keith, additional, Gordins, Pavel, additional, Graf, Stefan, additional, Gräf, Stefan, additional, Greene, Daniel, additional, Greenhalgh, Alan, additional, Greinacher, Andreas, additional, Grigoriadou, Sofia, additional, Grozeva, Detelina, additional, Hackett, Scott, additional, Hadinnapola, Charaka, additional, Hague, Rosie, additional, Haimel, Matthias, additional, Halmagyi, Csaba, additional, Hammerton, Tracey, additional, Hart, Daniel, additional, Hayman, Grant, additional, Heemskerk, Johan W.M., additional, Henderson, Robert, additional, Hensiek, Anke, additional, Henskens, Yvonne, additional, Herwadkar, Archana, additional, Holden, Simon, additional, Holder, Muriel, additional, Holder, Susan, additional, Hu, Fengyuan, additional, Huis in’t Veld, Anna, additional, Huissoon, Aarnoud, additional, Humbert, Marc, additional, Hurst, Jane, additional, James, Roger, additional, Jolles, Stephen, additional, Josifova, Dragana, additional, Kazmi, Rashid, additional, Keeling, David, additional, Kelleher, Peter, additional, Kelly, Anne M., additional, Kennedy, Fiona, additional, Kiely, David, additional, Kingston, Nathalie, additional, Koziell, Ania, additional, Krishnakumar, Deepa, additional, Kuijpers, Taco W., additional, Kuijpers, Taco, additional, Kumararatne, Dinakantha, additional, Kurian, Manju, additional, Laffan, Michael A., additional, Lambert, Michele P., additional, Allen, Hana Lango, additional, Lango-Allen, Hana, additional, Lawrie, Allan, additional, Lear, Sara, additional, Lees, Melissa, additional, Lentaigne, Claire, additional, Liesner, Ri, additional, Linger, Rachel, additional, Longhurst, Hilary, additional, Lorenzo, Lorena, additional, Louka, Eleni, additional, Machado, Rajiv, additional, Ross, Rob Mackenzie, additional, MacLaren, Robert, additional, Maher, Eamonn, additional, Maimaris, Jesmeen, additional, Mangles, Sarah, additional, Manson, Ania, additional, Markus, Hugh S., additional, Martin, Jennifer, additional, Masati, Larahmie, additional, Mathias, Mary, additional, Matser, Vera, additional, Maw, Anna, additional, McDermott, Elizabeth, additional, McJannet, Coleen, additional, Meacham, Stuart, additional, Meehan, Sharon, additional, Mehta, Sarju, additional, Michaelides, Michel, additional, Millar, Carolyn M., additional, Moledina, Shahin, additional, Moore, Anthony, additional, Morrell, Nicholas, additional, Mumford, Andrew, additional, Murng, Sai, additional, Murphy, Elaine, additional, Nejentsev, Sergey, additional, Noorani, Sadia, additional, Nurden, Paquita, additional, Oksenhendler, Eric, additional, Othman, Shokri, additional, Ouwehand, Willem H., additional, Papadia, Sofia, additional, Parker, Alasdair, additional, Pasi, John, additional, Patch, Chris, additional, Payne, Jeanette, additional, Peacock, Andrew, additional, Peerlinck, Kathelijne, additional, Penkett, Christopher J., additional, Pepke-Zaba, Joanna, additional, Perry, David, additional, Perry, David J., additional, Pollock, Val, additional, Polwarth, Gary, additional, Ponsford, Mark, additional, Qasim, Waseem, additional, Quinti, Isabella, additional, Rankin, Stuart, additional, Rankin, Julia, additional, Raymond, F. Lucy, additional, Rayner-Matthews, Paula, additional, Rehnstrom, Karola, additional, Reid, Evan, additional, Rhodes, Christopher J., additional, Richards, Michael, additional, Richardson, Sylvia, additional, Richter, Alex, additional, Roberts, Irene, additional, Rondina, Matthew, additional, Rosser, Elisabeth, additional, Roughley, Catherine, additional, Roy, Noémi, additional, Rue-Albrecht, Kevin, additional, Samarghitean, Crina, additional, Sanchis-Juan, Alba, additional, Sandford, Richard, additional, Santra, Saikat, additional, Sargur, Ravishankar, additional, Savic, Sinisa, additional, Schotte, Gwen, additional, Schulman, Sol, additional, Schulze, Harald, additional, Scott, Richard, additional, Scully, Marie, additional, Seneviratne, Suranjith, additional, Sewell, Carrock, additional, Shamardina, Olga, additional, Shipley, Debbie, additional, Simeoni, Ilenia, additional, Sivapalaratnam, Suthesh, additional, Smith, Kenneth G.C., additional, Sohal, Aman, additional, Southgate, Laura, additional, Staines, Simon, additional, Staples, Emily, additional, Stark, Hannah, additional, Stauss, Hans, additional, Stein, Penelope, additional, Stock, Sophie, additional, Suntharalingam, Jay, additional, Talks, Kate, additional, Tan, Yvonne, additional, Thachil, Jecko, additional, Thaventhiran, James, additional, Thomas, Ellen, additional, Thomas, Moira, additional, Thompson, Dorothy, additional, Thrasher, Adrian, additional, Tischkowitz, Marc, additional, Titterton, Catherine, additional, Toh, Cheng-Hock, additional, Toshner, Mark, additional, Treacy, Carmen, additional, Trembath, Richard, additional, Tuna, Salih, additional, Turek, Wojciech, additional, Turro, Ernest, additional, Van Geet, Chris, additional, Veltman, Marijke, additional, Vogt, Julie, additional, von Ziegenweldt, Julie, additional, Vonk Noordegraaf, Anton, additional, Wakeling, Emma, additional, Wanjiku, Ivy, additional, Warner, Timothy Q., additional, Wassmer, Evangeline, additional, Watkins, Hugh, additional, Watt, Christopher, additional, Webster, ndrew, additional, Welch, Steve, additional, Westbury, Sarah, additional, Wharton, John, additional, Whitehorn, Deborah, additional, Wilkins, Martin, additional, Willcocks, Lisa, additional, Williamson, Catherine, additional, Woods, Geoffrey, additional, Woods, Geoff, additional, Wort, John, additional, Yeatman, Nigel, additional, Yong, Patrick, additional, Young, Tim, additional, and Yu, Ping, additional

Published
2018
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57. Rare variants in GP1BB are responsible for autosomal dominant macrothrombocytopenia

Author

Sub Crystal and Structural Chemistry, Crystal and Structural Chemistry, Sivapalaratnam, Suthesh, Westbury, Sarah K., Stephens, Jonathan C., Greene, Daniel, Downes, Kate, Kelly, Anne M., Lentaigne, Claire, Astle, William J., Huizinga, Eric G., Nurden, Paquita, Papadia, Sofia, Peerlinck, Kathelijne, Penkett, Christopher J., Perry, David J., Roughley, Catherine, Simeoni, Ilenia, Stirrups, Kathleen E, Hart, Daniel P., Tait, R. Campbell, Mumford, Andrew D., Laffan, Michael A., Freson, Kathleen, Ouwehand, Willem H., Kunishima, Shinji, Turro, Ernest, Sub Crystal and Structural Chemistry, Crystal and Structural Chemistry, Sivapalaratnam, Suthesh, Westbury, Sarah K., Stephens, Jonathan C., Greene, Daniel, Downes, Kate, Kelly, Anne M., Lentaigne, Claire, Astle, William J., Huizinga, Eric G., Nurden, Paquita, Papadia, Sofia, Peerlinck, Kathelijne, Penkett, Christopher J., Perry, David J., Roughley, Catherine, Simeoni, Ilenia, Stirrups, Kathleen E, Hart, Daniel P., Tait, R. Campbell, Mumford, Andrew D., Laffan, Michael A., Freson, Kathleen, Ouwehand, Willem H., Kunishima, Shinji, and Turro, Ernest

Published
2017

58. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

Author

UMC Utrecht, Cardiovasculaire Epidemiologie, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Hendricks, Audrey E., Bochukova, Elena G., Marenne, Gaëlle, Keogh, Julia M., Atanassova, Neli, Bounds, Rebecca, Wheeler, Eleanor, Mistry, Vanisha, Henning, Elana, Körner, Antje, Muddyman, Dawn, McCarthy, Shane, Hinney, Anke, Hebebrand, Johannes, Scott, Robert A., Langenberg, Claudia, Wareham, Nick J., Surendran, Praveen, Howson, Joanna M M, Butterworth, Adam S., Danesh, John, Nordestgaard, Børge G., Nielsen, Sune F., Afzal, Shoaib, Papadia, Sofia, Ashford, Sofie, Garg, Sumedha, Millhauser, Glenn L., Palomino, Rafael I., Kwasniewska, Alexandra, Tachmazidou, Ioanna, O'Rahilly, Stephen, Zeggini, Eleftheria, Barroso, Inês, Farooqi, I. Sadaf, Benzeval, Michaela, Burton, Jonathan, Buck, Nicholas, Jäckle, Annette, Kumari, Meena, Laurie, Heather, Lynn, Peter, Pudney, Stephen, Rabe, Birgitta, Wolke, Dieter, Overvad, Kim, Tjønneland, Anne, Clavel-Chapelon, Francoise, Kaaks, Rudolf, Boeing, Heiner, Trichopoulou, Antonia, Ferrari, Pietro, Palli, Domenico, Krogha, Vittorio, Panico, Salvatore, Tuminoa, Rosario, Matullo, Giuseppe, Boer, Jolanda Ma, Van Der Schouw, Yvonne, Weiderpass, Elisabete, Quiros, J. Ramon, Sánchez, María José, Navarro, Carmen, Moreno-Iribas, Conchi, Arriola, Larraitz, Melander, Olle, Wennberg, Patrik, Key, Timothy J., Riboli, Elio, Al-Turki, Saeed, Anderson, Carl A, Anney, Richard, Antony, Dinu, Soler Artigas, María, Ayub, Muhammad, Bala, Senduran, Barrett, Jeffrey C, Beales, Phil, Bentham, Jamie, Bhattacharyaa, Shoumo, Birney, Ewan, Blackwooda, Douglas, Bobrow, Martin, Bolton, Patrick F., Boustred, Chris, Breen, Gerome, Calissanoa, Mattia, Carss, Keren, Charlton, Ruth, Chatterjee, Krishna, Chen, Lu, Ciampia, Antonio, Cirak, Sebahattin, Clapham, Peter, Clement, Gail, Coates, Guy, Coccaa, Massimiliano, Collier, David A, Cosgrove, Catherine, Coxa, Tony, Craddock, Nick, Crooks, Lucy, Curran, Sarah, Curtis, David, Daly, Allan, Danecek, Petr, Day, Ian N M, Day-Williams, Aaron G, Dominiczak, Anna, Down, Thomas, Du, Yuanping, Dunham, Ian, Durbin, Richard, Edkins, Sarah, Ekong, Rosemary, Ellis, Peter, Evansa, David M., FitzPatrick, David R., Flicek, Paul, Floyd, James S., Foley, A. Reghan, Franklin, Christopher S., Futema, Marta, Gallagher, Louise, Gaunt, Tom R., Geihs, Matthias, Geschwind, Daniel H., Greenwood, Celia M.T., Griffin, Heather, Grozeva, Detelina, Guo, Xiaosen, Guo, Xueqin, Gurling, Hugh, Hart, Deborah J., Holmans, Peter A, Howie, Bryan, Huang, Jie, Huang, Liren, Hubbard, Tim, Humphries, Steve E., Hurles, Matthew E., Hysi, Pirro G., Iotchkova, Valentina, Jackson, David K., Jamshidi, Yalda, Joyce, Chris, Karczewski, Konrad J., Kaye, Jane, Keane, Thomas, Kemp, John P., Kennedy, Karen, Kent, Alastair, Khawaja, Farrah, Van Kogelenberg, Margriet, Kolb-Kokocinski, Anja, Lachance, Genevieve, Langford, Cordelia, Lawson, Daniel, Lee, Irene, Lek, Monkol, Li, Rui, Li, Yingrui, Liang, Jieqin, Lin, Hong, Liu, Ryan, Lönnqvist, Jouko, Lopes, Luis R., Lopes, Margarida, MacArthur, Daniel G., Mangino, Massimo, Marchini, Jonathan, Maslen, John, Mathieson, Iain, McGuffin, Peter, McIntosh, Andrew M., McKechanie, Andrew G., McQuillin, Andrew, Memari, Yasin, Metrustry, Sarah, Migone, Nicola, Min, Josine L., Mitchison, Hannah M, Moayyeri, Alireza, Morris, Andrew D., Morris, James, Muntoni, Francesco, Northstone, Kate, O'Donovan, Michael C., Onoufriadis, Alexandros, Oualkacha, Karim, Owen, Michael J, Palotie, Aarno, Panoutsopoulou, Kalliope, Parker, Victoria, Parr, Jeremy R., Paternoster, Lavinia, Paunio, Tiina, Payne, Felicity, Payne, Stewart J., Perry, John R. B., Pietilainen, Olli, Plagnol, Vincent, Pollitt, Rebecca C., Porteous, David J., Povey, Sue, Quail, Michael A., Quaye, Lydia, Raymond, F. Lucy, Rehnström, Karola, Richards, J Brent, Ridout, Cheryl K., Ring, Susan M., Ritchie, Graham R.S., Roberts, Nicola, Robinson, Rachel L., Savage, David B., Scambler, Peter, Schiffels, Stephan, Schmidts, Miriam, Schoenmakers, Nadia, Scott, Richard H., Semple, Robert K., Serra, Eva, Sharp, Sally I., Shaw, Adam, Shihab, Hashem A., Shin, So Youn, Skuse, David, Small, Kerrin S, Smee, Carol, Smith, Blair H., Davey Smith, George, Soranzo, Nicole, Southam, Lorraine, Spasic-Boskovic, Olivera, Spector, Timothy D, St Clair, David, St Pourcain, Beate, Stalker, Jim, Stevens, Elizabeth, Sun, Jianping, Surdulescu, Gabriela L, Suvisaari, Jaana, Syrris, Petros, Taylor, Rohan, Tian, Jing, Timpson, Nicholas J., Tobin, Martin D, Valdes, Ana M., Vandersteen, Anthony M., Vijayarangakannan, Parthiban, Visscher, Peter M., Wain, Louise V., Walter, Klaudia, Walters, James T.R., Wang, Guangbiao, Wang, Jun, Wang, Nai-Yu, Ward, Kirsten, Whyte, Tamieka, Williams, Hywel J., Williamson, Kathleen A., Wilson, Crispian, Wilson, Scott G., Wong, Kim, Xu, Changjiang, Yang, Jian, Zhang, Feng, Zhang, Pingbo, Zheng, Hou Feng, UMC Utrecht, Cardiovasculaire Epidemiologie, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Hendricks, Audrey E., Bochukova, Elena G., Marenne, Gaëlle, Keogh, Julia M., Atanassova, Neli, Bounds, Rebecca, Wheeler, Eleanor, Mistry, Vanisha, Henning, Elana, Körner, Antje, Muddyman, Dawn, McCarthy, Shane, Hinney, Anke, Hebebrand, Johannes, Scott, Robert A., Langenberg, Claudia, Wareham, Nick J., Surendran, Praveen, Howson, Joanna M M, Butterworth, Adam S., Danesh, John, Nordestgaard, Børge G., Nielsen, Sune F., Afzal, Shoaib, Papadia, Sofia, Ashford, Sofie, Garg, Sumedha, Millhauser, Glenn L., Palomino, Rafael I., Kwasniewska, Alexandra, Tachmazidou, Ioanna, O'Rahilly, Stephen, Zeggini, Eleftheria, Barroso, Inês, Farooqi, I. Sadaf, Benzeval, Michaela, Burton, Jonathan, Buck, Nicholas, Jäckle, Annette, Kumari, Meena, Laurie, Heather, Lynn, Peter, Pudney, Stephen, Rabe, Birgitta, Wolke, Dieter, Overvad, Kim, Tjønneland, Anne, Clavel-Chapelon, Francoise, Kaaks, Rudolf, Boeing, Heiner, Trichopoulou, Antonia, Ferrari, Pietro, Palli, Domenico, Krogha, Vittorio, Panico, Salvatore, Tuminoa, Rosario, Matullo, Giuseppe, Boer, Jolanda Ma, Van Der Schouw, Yvonne, Weiderpass, Elisabete, Quiros, J. Ramon, Sánchez, María José, Navarro, Carmen, Moreno-Iribas, Conchi, Arriola, Larraitz, Melander, Olle, Wennberg, Patrik, Key, Timothy J., Riboli, Elio, Al-Turki, Saeed, Anderson, Carl A, Anney, Richard, Antony, Dinu, Soler Artigas, María, Ayub, Muhammad, Bala, Senduran, Barrett, Jeffrey C, Beales, Phil, Bentham, Jamie, Bhattacharyaa, Shoumo, Birney, Ewan, Blackwooda, Douglas, Bobrow, Martin, Bolton, Patrick F., Boustred, Chris, Breen, Gerome, Calissanoa, Mattia, Carss, Keren, Charlton, Ruth, Chatterjee, Krishna, Chen, Lu, Ciampia, Antonio, Cirak, Sebahattin, Clapham, Peter, Clement, Gail, Coates, Guy, Coccaa, Massimiliano, Collier, David A, Cosgrove, Catherine, Coxa, Tony, Craddock, Nick, Crooks, Lucy, Curran, Sarah, Curtis, David, Daly, Allan, Danecek, Petr, Day, Ian N M, Day-Williams, Aaron G, Dominiczak, Anna, Down, Thomas, Du, Yuanping, Dunham, Ian, Durbin, Richard, Edkins, Sarah, Ekong, Rosemary, Ellis, Peter, Evansa, David M., FitzPatrick, David R., Flicek, Paul, Floyd, James S., Foley, A. Reghan, Franklin, Christopher S., Futema, Marta, Gallagher, Louise, Gaunt, Tom R., Geihs, Matthias, Geschwind, Daniel H., Greenwood, Celia M.T., Griffin, Heather, Grozeva, Detelina, Guo, Xiaosen, Guo, Xueqin, Gurling, Hugh, Hart, Deborah J., Holmans, Peter A, Howie, Bryan, Huang, Jie, Huang, Liren, Hubbard, Tim, Humphries, Steve E., Hurles, Matthew E., Hysi, Pirro G., Iotchkova, Valentina, Jackson, David K., Jamshidi, Yalda, Joyce, Chris, Karczewski, Konrad J., Kaye, Jane, Keane, Thomas, Kemp, John P., Kennedy, Karen, Kent, Alastair, Khawaja, Farrah, Van Kogelenberg, Margriet, Kolb-Kokocinski, Anja, Lachance, Genevieve, Langford, Cordelia, Lawson, Daniel, Lee, Irene, Lek, Monkol, Li, Rui, Li, Yingrui, Liang, Jieqin, Lin, Hong, Liu, Ryan, Lönnqvist, Jouko, Lopes, Luis R., Lopes, Margarida, MacArthur, Daniel G., Mangino, Massimo, Marchini, Jonathan, Maslen, John, Mathieson, Iain, McGuffin, Peter, McIntosh, Andrew M., McKechanie, Andrew G., McQuillin, Andrew, Memari, Yasin, Metrustry, Sarah, Migone, Nicola, Min, Josine L., Mitchison, Hannah M, Moayyeri, Alireza, Morris, Andrew D., Morris, James, Muntoni, Francesco, Northstone, Kate, O'Donovan, Michael C., Onoufriadis, Alexandros, Oualkacha, Karim, Owen, Michael J, Palotie, Aarno, Panoutsopoulou, Kalliope, Parker, Victoria, Parr, Jeremy R., Paternoster, Lavinia, Paunio, Tiina, Payne, Felicity, Payne, Stewart J., Perry, John R. B., Pietilainen, Olli, Plagnol, Vincent, Pollitt, Rebecca C., Porteous, David J., Povey, Sue, Quail, Michael A., Quaye, Lydia, Raymond, F. Lucy, Rehnström, Karola, Richards, J Brent, Ridout, Cheryl K., Ring, Susan M., Ritchie, Graham R.S., Roberts, Nicola, Robinson, Rachel L., Savage, David B., Scambler, Peter, Schiffels, Stephan, Schmidts, Miriam, Schoenmakers, Nadia, Scott, Richard H., Semple, Robert K., Serra, Eva, Sharp, Sally I., Shaw, Adam, Shihab, Hashem A., Shin, So Youn, Skuse, David, Small, Kerrin S, Smee, Carol, Smith, Blair H., Davey Smith, George, Soranzo, Nicole, Southam, Lorraine, Spasic-Boskovic, Olivera, Spector, Timothy D, St Clair, David, St Pourcain, Beate, Stalker, Jim, Stevens, Elizabeth, Sun, Jianping, Surdulescu, Gabriela L, Suvisaari, Jaana, Syrris, Petros, Taylor, Rohan, Tian, Jing, Timpson, Nicholas J., Tobin, Martin D, Valdes, Ana M., Vandersteen, Anthony M., Vijayarangakannan, Parthiban, Visscher, Peter M., Wain, Louise V., Walter, Klaudia, Walters, James T.R., Wang, Guangbiao, Wang, Jun, Wang, Nai-Yu, Ward, Kirsten, Whyte, Tamieka, Williams, Hywel J., Williamson, Kathleen A., Wilson, Crispian, Wilson, Scott G., Wong, Kim, Xu, Changjiang, Yang, Jian, Zhang, Feng, Zhang, Pingbo, and Zheng, Hou Feng

Published
2017

59. Biallelic Mutation of ARHGEF18, Involved in the Determination of Epithelial Apicobasal Polarity, Causes Adult-Onset Retinal Degeneration

Author

Arno, Gavin, primary, Carss, Keren J., additional, Hull, Sarah, additional, Zihni, Ceniz, additional, Robson, Anthony G., additional, Fiorentino, Alessia, additional, Hardcastle, Alison J., additional, Holder, Graham E., additional, Cheetham, Michael E., additional, Plagnol, Vincent, additional, Moore, Anthony T., additional, Raymond, F. Lucy, additional, Matter, Karl, additional, Balda, Maria S., additional, Webster, Andrew R., additional, Black, Graeme, additional, Hall, Georgina, additional, Ingram, Stuart, additional, Gillespie, Rachel, additional, Manson, Forbes, additional, Sergouniotis, Panagiotis, additional, Inglehearn, Chris, additional, Toomes, Carmel, additional, Ali, Manir, additional, McKibbin, Martin, additional, Poulter, James, additional, Khan, Kamron, additional, Lord, Emma, additional, Nemeth, Andrea, additional, Downes, Susan, additional, Halford, Stephanie, additional, Yu, Jing, additional, Lise, Stefano, additional, Arno, Gavin, additional, Ponitkos, Nikos, additional, Michaelides, Michel, additional, van Heyningen, Veronica, additional, Aitman, Timothy, additional, Alachkar, Hana, additional, Ali, Sonia, additional, Allen, Louise, additional, Allsup, David, additional, Ambegaonkar, Gautum, additional, Anderson, Julie, additional, Antrobus, Richard, additional, Armstrong, Ruth, additional, Arumugakani, Gururaj, additional, Ashford, Sofie, additional, Astle, William, additional, Attwood, Antony, additional, Austin, Steve, additional, Bacchelli, Chiara, additional, Bakchoul, Tamam, additional, Bariana, Tadbir K., additional, Baxendale, Helen, additional, Bennett, David, additional, Bethune, Claire, additional, Bibi, Shahnaz, additional, Bitner-Glindzicz, Maria, additional, Bleda, Marta, additional, Boggard, Harm, additional, Bolton-Maggs, Paula, additional, Booth, Claire, additional, Bradley, John R., additional, Brady, Angie, additional, Brown, Matthew, additional, Browning, Michael, additional, Bryson, Christine, additional, Burns, Siobhan, additional, Calleja, Paul, additional, Canham, Natalie, additional, Carmichael, Jenny, additional, Carss, Keren, additional, Caulfield, Mark, additional, Chalmers, Elizabeth, additional, Chandra, Anita, additional, Chinnery, Patrick, additional, Chitre, Manali, additional, Church, Colin, additional, Clement, Emma, additional, Clements-Brod, Naomi, additional, Clowes, Virginia, additional, Coghlan, Gerry, additional, Collins, Peter, additional, Cooper, Nichola, additional, Creaser-Myers, Amanda, additional, DaCosta, Rosa, additional, Daugherty, Louise, additional, Davies, Sophie, additional, Davis, John, additional, De Vries, Minka, additional, Deegan, Patrick, additional, Deevi, Sri V.V., additional, Deshpande, Charu, additional, Devlin, Lisa, additional, Dewhurst, Eleanor, additional, Doffinger, Rainer, additional, Dormand, Natalie, additional, Drewe, Elizabeth, additional, Edgar, David, additional, Egner, William, additional, Erber, Wendy N., additional, Erwood, Marie, additional, Everington, Tamara, additional, Favier, Remi, additional, Firth, Helen, additional, Fletcher, Debra, additional, Flinter, Frances, additional, Fox, James C., additional, Frary, Amy, additional, Freson, Kathleen, additional, Furie, Bruce, additional, Furnell, Abigail, additional, Gale, Daniel, additional, Gardham, Alice, additional, Gattens, Michael, additional, Ghali, Neeti, additional, Ghataorhe, Pavandeep K., additional, Ghurye, Rohit, additional, Gibbs, Simon, additional, Gilmour, Kimberley, additional, Gissen, Paul, additional, Goddard, Sarah, additional, Gomez, Keith, additional, Gordins, Pavel, additional, Gräf, Stefan, additional, Greene, Daniel, additional, Greenhalgh, Alan, additional, Greinacher, Andreas, additional, Grigoriadou, Sofia, additional, Grozeva, Detelina, additional, Hackett, Scott, additional, Hadinnapola, Charaka, additional, Hague, Rosie, additional, Haimel, Matthias, additional, Halmagyi, Csaba, additional, Hammerton, Tracey, additional, Hart, Daniel, additional, Hayman, Grant, additional, Heemskerk, Johan W.M., additional, Henderson, Robert, additional, Hensiek, Anke, additional, Henskens, Yvonne, additional, Herwadkar, Archana, additional, Holden, Simon, additional, Holder, Muriel, additional, Holder, Susan, additional, Hu, Fengyuan, additional, Huissoon, Aarnoud, additional, Humbert, Marc, additional, Hurst, Jane, additional, James, Roger, additional, Jolles, Stephen, additional, Josifova, Dragana, additional, Kazmi, Rashid, additional, Keeling, David, additional, Kelleher, Peter, additional, Kelly, Anne M., additional, Kennedy, Fiona, additional, Kiely, David, additional, Kingston, Nathalie, additional, Koziell, Ania, additional, Krishnakumar, Deepa, additional, Kuijpers, Taco W., additional, Kumararatne, Dinakantha, additional, Kurian, Manju, additional, Laffan, Michael A., additional, Lambert, Michele P., additional, Allen, Hana Lango, additional, Lawrie, Allan, additional, Lear, Sara, additional, Lees, Melissa, additional, Lentaigne, Claire, additional, Liesner, Ri, additional, Linger, Rachel, additional, Longhurst, Hilary, additional, Lorenzo, Lorena, additional, Machado, Rajiv, additional, Mackenzie, Rob, additional, MacLaren, Robert, additional, Maher, Eamonn, additional, Maimaris, Jesmeen, additional, Mangles, Sarah, additional, Manson, Ania, additional, Mapeta, Rutendo, additional, Markus, Hugh S., additional, Martin, Jennifer, additional, Masati, Larahmie, additional, Mathias, Mary, additional, Matser, Vera, additional, Maw, Anna, additional, McDermott, Elizabeth, additional, McJannet, Coleen, additional, Meacham, Stuart, additional, Meehan, Sharon, additional, Megy, Karyn, additional, Mehta, Sarju, additional, Millar, Carolyn M., additional, Moledina, Shahin, additional, Moore, Anthony, additional, Morrell, Nicholas, additional, Mumford, Andrew, additional, Murng, Sai, additional, Murphy, Elaine, additional, Nejentsev, Sergey, additional, Noorani, Sadia, additional, Nurden, Paquita, additional, Oksenhendler, Eric, additional, Ouwehand, Willem H., additional, Papadia, Sofia, additional, Park, Soo-Mi, additional, Parker, Alasdair, additional, Pasi, John, additional, Patch, Chris, additional, Paterson, Joan, additional, Payne, Jeanette, additional, Peacock, Andrew, additional, Peerlinck, Kathelijne, additional, Penkett, Christopher J., additional, Pepke-Zaba, Joanna, additional, Perry, David J., additional, Pollock, Val, additional, Polwarth, Gary, additional, Ponsford, Mark, additional, Qasim, Waseem, additional, Quinti, Isabella, additional, Rankin, Stuart, additional, Rankin, Julia, additional, Rehnstrom, Karola, additional, Reid, Evan, additional, Rhodes, Christopher J., additional, Richards, Michael, additional, Richardson, Sylvia, additional, Richter, Alex, additional, Roberts, Irene, additional, Rondina, Matthew, additional, Rosser, Elisabeth, additional, Roughley, Catherine, additional, Rue-Albrecht, Kevin, additional, Samarghitean, Crina, additional, Sanchis-Juan, Alba, additional, Sandford, Richard, additional, Santra, Saikat, additional, Sargur, Ravishankar, additional, Savic, Sinisa, additional, Schulman, Sol, additional, Schulze, Harald, additional, Scott, Richard, additional, Scully, Marie, additional, Seneviratne, Suranjith, additional, Sewell, Carrock, additional, Shamardina, Olga, additional, Shipley, Debbie, additional, Simeoni, Ilenia, additional, Sivapalaratnam, Suthesh, additional, Smith, Kenneth, additional, Sohal, Aman, additional, Southgate, Laura, additional, Staines, Simon, additional, Staples, Emily, additional, Stauss, Hans, additional, Stein, Penelope, additional, Stephens, Jonathan, additional, Stirrups, Kathleen, additional, Stock, Sophie, additional, Suntharalingam, Jay, additional, Tait, R. Campbell, additional, Talks, Kate, additional, Tan, Yvonne, additional, Thachil, Jecko, additional, Thaventhiran, James, additional, Thomas, Ellen, additional, Thomas, Moira, additional, Thompson, Dorothy, additional, Thrasher, Adrian, additional, Tischkowitz, Marc, additional, Titterton, Catherine, additional, Toh, Cheng-Hock, additional, Toshner, Mark, additional, Treacy, Carmen, additional, Trembath, Richard, additional, Tuna, Salih, additional, Turek, Wojciech, additional, Turro, Ernest, additional, Van Geet, Chris, additional, Veltman, Marijke, additional, Vogt, Julie, additional, von Ziegenweldt, Julie, additional, Vonk Noordegraaf, Anton, additional, Wakeling, Emma, additional, Wanjiku, Ivy, additional, Warner, Timothy Q., additional, Wassmer, Evangeline, additional, Watkins, Hugh, additional, Webster, Andrew, additional, Welch, Steve, additional, Westbury, Sarah, additional, Wharton, John, additional, Whitehorn, Deborah, additional, Wilkins, Martin, additional, Willcocks, Lisa, additional, Williamson, Catherine, additional, Woods, Geoffrey, additional, Wort, John, additional, Yeatman, Nigel, additional, Yong, Patrick, additional, Young, Tim, additional, and Yu, Ping, additional

Published
2017
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60. Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Author

Carss, Keren J., primary, Arno, Gavin, additional, Erwood, Marie, additional, Stephens, Jonathan, additional, Sanchis-Juan, Alba, additional, Hull, Sarah, additional, Megy, Karyn, additional, Grozeva, Detelina, additional, Dewhurst, Eleanor, additional, Malka, Samantha, additional, Plagnol, Vincent, additional, Penkett, Christopher, additional, Stirrups, Kathleen, additional, Rizzo, Roberta, additional, Wright, Genevieve, additional, Josifova, Dragana, additional, Bitner-Glindzicz, Maria, additional, Scott, Richard H., additional, Clement, Emma, additional, Allen, Louise, additional, Armstrong, Ruth, additional, Brady, Angela F., additional, Carmichael, Jenny, additional, Chitre, Manali, additional, Henderson, Robert H.H., additional, Hurst, Jane, additional, MacLaren, Robert E., additional, Murphy, Elaine, additional, Paterson, Joan, additional, Rosser, Elisabeth, additional, Thompson, Dorothy A., additional, Wakeling, Emma, additional, Ouwehand, Willem H., additional, Michaelides, Michel, additional, Moore, Anthony T., additional, Webster, Andrew R., additional, Raymond, F. Lucy, additional, Aitman, Timothy, additional, Alachkar, Hana, additional, Ali, Sonia, additional, Allsup, David, additional, Ambegaonkar, Gautum, additional, Anderson, Julie, additional, Antrobus, Richard, additional, Arumugakani, Gururaj, additional, Ashford, Sofie, additional, Astle, William, additional, Attwood, Antony, additional, Austin, Steve, additional, Bacchelli, Chiara, additional, Bakchoul, Tamam, additional, Bariana, Tadbir K., additional, Baxendale, Helen, additional, Bennett, David, additional, Bethune, Claire, additional, Bibi, Shahnaz, additional, Bleda, Marta, additional, Boggard, Harm, additional, Bolton-Maggs, Paula, additional, Booth, Claire, additional, Bradley, John R., additional, Brady, Angie, additional, Brown, Matthew, additional, Browning, Michael, additional, Bryson, Christine, additional, Burns, Siobhan, additional, Calleja, Paul, additional, Canham, Natalie, additional, Carss, Keren, additional, Caulfield, Mark, additional, Chalmers, Elizabeth, additional, Chandra, Anita, additional, Chinnery, Patrick, additional, Church, Colin, additional, Clements-Brod, Naomi, additional, Clowes, Virginia, additional, Coghlan, Gerry, additional, Collins, Peter, additional, Cooper, Nichola, additional, Creaser-Myers, Amanda, additional, DaCosta, Rosa, additional, Daugherty, Louise, additional, Davies, Sophie, additional, Davis, John, additional, De Vries, Minka, additional, Deegan, Patrick, additional, Deevi, Sri V.V., additional, Deshpande, Charu, additional, Devlin, Lisa, additional, Doffinger, Rainer, additional, Dormand, Natalie, additional, Drewe, Elizabeth, additional, Edgar, David, additional, Egner, William, additional, Erber, Wendy N., additional, Everington, Tamara, additional, Favier, Remi, additional, Firth, Helen, additional, Fletcher, Debra, additional, Flinter, Frances, additional, Fox, James C., additional, Frary, Amy, additional, Freson, Kathleen, additional, Furie, Bruce, additional, Furnell, Abigail, additional, Gale, Daniel, additional, Gardham, Alice, additional, Gattens, Michael, additional, Ghali, Neeti, additional, Ghataorhe, Pavandeep K., additional, Ghurye, Rohit, additional, Gibbs, Simon, additional, Gilmour, Kimberley, additional, Gissen, Paul, additional, Goddard, Sarah, additional, Gomez, Keith, additional, Gordins, Pavel, additional, Gräf, Stefan, additional, Greene, Daniel, additional, Greenhalgh, Alan, additional, Greinacher, Andreas, additional, Grigoriadou, Sofia, additional, Hackett, Scott, additional, Hadinnapola, Charaka, additional, Hague, Rosie, additional, Haimel, Matthias, additional, Halmagyi, Csaba, additional, Hammerton, Tracey, additional, Hart, Daniel, additional, Hayman, Grant, additional, Heemskerk, Johan W.M., additional, Henderson, Robert, additional, Hensiek, Anke, additional, Henskens, Yvonne, additional, Herwadkar, Archana, additional, Holden, Simon, additional, Holder, Muriel, additional, Holder, Susan, additional, Hu, Fengyuan, additional, Huissoon, Aarnoud, additional, Humbert, Marc, additional, James, Roger, additional, Jolles, Stephen, additional, Kazmi, Rashid, additional, Keeling, David, additional, Kelleher, Peter, additional, Kelly, Anne M., additional, Kennedy, Fiona, additional, Kiely, David, additional, Kingston, Nathalie, additional, Koziell, Ania, additional, Krishnakumar, Deepa, additional, Kuijpers, Taco W., additional, Kumararatne, Dinakantha, additional, Kurian, Manju, additional, Laffan, Michael A., additional, Lambert, Michele P., additional, Allen, Hana Lango, additional, Lawrie, Allan, additional, Lear, Sara, additional, Lees, Melissa, additional, Lentaigne, Claire, additional, Liesner, Ri, additional, Linger, Rachel, additional, Longhurst, Hilary, additional, Lorenzo, Lorena, additional, Machado, Rajiv, additional, Mackenzie, Rob, additional, MacLaren, Robert, additional, Maher, Eamonn, additional, Maimaris, Jesmeen, additional, Mangles, Sarah, additional, Manson, Ania, additional, Mapeta, Rutendo, additional, Markus, Hugh S., additional, Martin, Jennifer, additional, Masati, Larahmie, additional, Mathias, Mary, additional, Matser, Vera, additional, Maw, Anna, additional, McDermott, Elizabeth, additional, McJannet, Coleen, additional, Meacham, Stuart, additional, Meehan, Sharon, additional, Mehta, Sarju, additional, Millar, Carolyn M., additional, Moledina, Shahin, additional, Moore, Anthony, additional, Morrell, Nicholas, additional, Mumford, Andrew, additional, Murng, Sai, additional, Nejentsev, Sergey, additional, Noorani, Sadia, additional, Nurden, Paquita, additional, Oksenhendler, Eric, additional, Papadia, Sofia, additional, Park, Soo-Mi, additional, Parker, Alasdair, additional, Pasi, John, additional, Patch, Chris, additional, Payne, Jeanette, additional, Peacock, Andrew, additional, Peerlinck, Kathelijne, additional, Penkett, Christopher J., additional, Pepke-Zaba, Joanna, additional, Perry, David J., additional, Pollock, Val, additional, Polwarth, Gary, additional, Ponsford, Mark, additional, Qasim, Waseem, additional, Quinti, Isabella, additional, Rankin, Stuart, additional, Rankin, Julia, additional, Raymond, F. Lucy, additional, Rehnstrom, Karola, additional, Reid, Evan, additional, Rhodes, Christopher J., additional, Richards, Michael, additional, Richardson, Sylvia, additional, Richter, Alex, additional, Roberts, Irene, additional, Rondina, Matthew, additional, Roughley, Catherine, additional, Rue-Albrecht, Kevin, additional, Samarghitean, Crina, additional, Sandford, Richard, additional, Santra, Saikat, additional, Sargur, Ravishankar, additional, Savic, Sinisa, additional, Schulman, Sol, additional, Schulze, Harald, additional, Scott, Richard, additional, Scully, Marie, additional, Seneviratne, Suranjith, additional, Sewell, Carrock, additional, Shamardina, Olga, additional, Shipley, Debbie, additional, Simeoni, Ilenia, additional, Sivapalaratnam, Suthesh, additional, Smith, Kenneth, additional, Sohal, Aman, additional, Southgate, Laura, additional, Staines, Simon, additional, Staples, Emily, additional, Stauss, Hans, additional, Stein, Penelope, additional, Stock, Sophie, additional, Suntharalingam, Jay, additional, Tait, R. Campbell, additional, Talks, Kate, additional, Tan, Yvonne, additional, Thachil, Jecko, additional, Thaventhiran, James, additional, Thomas, Ellen, additional, Thomas, Moira, additional, Thompson, Dorothy, additional, Thrasher, Adrian, additional, Tischkowitz, Marc, additional, Titterton, Catherine, additional, Toh, Cheng-Hock, additional, Toshner, Mark, additional, Treacy, Carmen, additional, Trembath, Richard, additional, Tuna, Salih, additional, Turek, Wojciech, additional, Turro, Ernest, additional, Van Geet, Chris, additional, Veltman, Marijke, additional, Vogt, Julie, additional, von Ziegenweldt, Julie, additional, Vonk Noordegraaf, Anton, additional, Wanjiku, Ivy, additional, Warner, Timothy Q., additional, Wassmer, Evangeline, additional, Watkins, Hugh, additional, Webster, Andrew, additional, Welch, Steve, additional, Westbury, Sarah, additional, Wharton, John, additional, Whitehorn, Deborah, additional, Wilkins, Martin, additional, Willcocks, Lisa, additional, Williamson, Catherine, additional, Woods, Geoffrey, additional, Wort, John, additional, Yeatman, Nigel, additional, Yong, Patrick, additional, Young, Tim, additional, and Yu, Ping, additional

Published
2017
Full Text
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61. Phenotypic Characterization of EIF2AK4Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension

Author

Hadinnapola, Charaka, Bleda, Marta, Haimel, Matthias, Screaton, Nicholas, Swift, Andrew, Dorfmüller, Peter, Preston, Stephen D., Southwood, Mark, Hernandez-Sanchez, Jules, Martin, Jennifer, Treacy, Carmen, Yates, Katherine, Bogaard, Harm, Church, Colin, Coghlan, Gerry, Condliffe, Robin, Corris, Paul A., Gibbs, Simon, Girerd, Barbara, Holden, Simon, Humbert, Marc, Kiely, David G., Lawrie, Allan, Machado, Rajiv, MacKenzie Ross, Robert, Moledina, Shahin, Montani, David, Newnham, Michael, Peacock, Andrew, Pepke-Zaba, Joanna, Rayner-Matthews, Paula, Shamardina, Olga, Soubrier, Florent, Southgate, Laura, Suntharalingam, Jay, Toshner, Mark, Trembath, Richard, Noordegraaf, Anton Vonk, Wilkins, Martin R., Wort, Stephen J., Wharton, John, Gräf, Stefan, Morrell, Nicholas W., Aitman, Timothy, Bennett, David, Caulfield, Mark, Chinnery, Patrick, Gale, Daniel, Koziell, Ania, Kuijpers, Taco W, Laffan, Michael A, Maher, Eamonn, Markus, Hugh S, Ouwehand, Willem H, Perry, David, Raymond, F Lucy, Roberts, Irene, Smith, Kenneth, Thrasher, Adrian, Watkins, Hugh, Williamson, Catherine, Woods, Geoffrey, Ashford, Sofie, Bradley, John R, Fletcher, Debra, Hammerton, Tracey, James, Roger, Kingston, Nathalie, Ouwehand, Willem H, Penkett, Christopher J, Raymond, F Lucy, Stirrups, Kathleen, Veltman, Marijke, Young, Tim, Ashford, Sofie, Brown, Matthew, Clements-Brod, Naomi, Davis, John, Dewhurst, Eleanor, Erwood, Marie, Frary, Amy, Linger, Rachel, Papadia, Sofia, Rehnstrom, Karola, Stark, Hannah, Allsup, David, Austin, Steve, Bakchoul, Tamam, Bariana, Tadbir K, Bolton-Maggs, Paula, Chalmers, Elizabeth, Collins, Peter, Erber, Wendy N, Everington, Tamara, Favier, Remi, Freson, Kathleen, Furie, Bruce, Gattens, Michael, Gomez, Keith, Greene, Daniel, Greinacher, Andreas, Hart, Daniel, Heemskerk, Johan WM, Henskens, Yvonne, Kazmi, Rashid, Keeling, David, Kelly, Anne M, Laffan, Michael A, Lambert, Michele P, Lentaigne, Claire, Liesner, Ri, Mangles, Sarah, Mathias, Mary, Millar, Carolyn M, Mumford, Andrew, Nurden, Paquita, Ouwehand, Willem H, Papadia, Sofia, Payne, Jeanette, Pasi, John, Perry, David J, Peerlinck, Kathelijne, Richards, Michael, Rondina, Matthew, Roughley, Catherine, Schulman, Sol, Schulze, Harald, Scully, Marie, Sivapalaratnam, Suthesh, Tait, R Campbell, Talks, Kate, Thachil, Jecko, Turro, Ernest, Toh, Cheng-Hock, Van Geet, Chris, De Vries, Minka, Warner, Timothy Q, Westbury, Sarah, Furnell, Abigail, Mapeta, Rutendo, Simeoni, Ilenia, Staines, Simon, Stephens, Jonathan, Stirrups, Kathleen, Whitehorn, Deborah, Watt, Christopher, Attwood, Antony, Daugherty, Louise, Deevi, Sri VV, Halmagyi, Csaba, Hu, Fengyuan, James, Roger, Matser, Vera, Meacham, Stuart, Megy, Karyn, Penkett, Christopher J, Stirrups, Kathleen, Titterton, Catherine, Tuna, Salih, Yu, Ping, von Ziegenweldt, Julie, Astle, William, Carss, Keren, Greene, Daniel, Lango-Allen, Hana, Turro, Ernest, Astle, William, Greene, Daniel, Richardson, Sylvia, Turro, Ernest, Calleja, Paul, Rankin, Stuart, Turek, Wojciech, Bryson, Christine, Anderson, Julie, Fletcher, Debra, McJannet, Coleen, Stock, Sophie, Young, Tim, Wassmer, Evangeline, Sohal, Aman, Santra, Saikat, Vogt, Julie, Chitre, Manali, Krishnakumar, Deepa, Ambegaonkar, Gautum, Maw, Anna, Armstrong, Ruth, Park, Soo-Mi, Mehta, Sarju, Paterson, Joan, Carmichael, Jenny, Allen, Louise, Hensiek, Anke, Firth, Helen, Stein, Penelope, Deegan, Patrick, Doffinger, Rainer, Parker, Alasdair, Bitner-Glindzicz, Maria, Scott, Richard, Hurst, Jane, Rosser, Elisabeth, Lees, Melissa, Clement, Emma, Henderson, Robert, Thompson, Dorothy, Gardham, Alice, Gissen, Paul, Josifova, Dragana, Thomas, Ellen, Patch, Chris, Deshpande, Charu, Flinter, Frances, Holder, Muriel, Canham, Natalie, Wakeling, Emma, Holder, Susan, Ghali, Neeti, Brady, Angie, Clowes, Virginia, MacLaren, Robert, Webster, Andrew, Moore, Anthony, Arno, Gavin, Michaelides, Michel, Rankin, Julia, Kurian, Manju, Murphy, Elaine, Carss, Keren, Sanchis-Juan, Alba, Erwood, Marie, Dewhurst, Eleanor, Grozeva, Detelina, Raymond, F Lucy, Reid, Evan, Woods, Geoff, Tischkowitz, Marc, Sandford, Richard, Ali, Sonia, Creaser-Myers, Amanda, Cookson, Victoria, DaCosta, Rosa, Dormand, Natalie, Ghataorhe, Pavandeep K, Greenhalgh, Alan, Huis in’t Veld, Anna, Kennedy, Fiona, Mackenzie Ross, Rob, Masati, Larahmie, Meehan, Sharon, Othman, Shokri, Pollock, Val, Polwarth, Gary, Rhodes, Christopher J, Rue-Albrecht, Kevin, Schotte, Gwen, Shipley, Debbie, Tan, Yvonne, Wanjiku, Ivy, Wort, John, Smith, Kenneth, Kuijpers, Taco, Thrasher, Adrian, Thaventhiran, James, Brown, Matthew, Lango Allen, Hana, Simeoni, Ilenia, Staples, Emily, Samarghitean, Crina, Alachkar, Hana, Antrobus, Richard, Arumugakani, Gururaj, Bacchelli, Chiara, Baxendale, Helen, Bethune, Claire, Bibi, Shahnaz, Booth, Claire, Browning, Michael, Burns, Siobhan, Chandra, Anita, Cooper, Nichola, Davies, Sophie, Devlin, Lisa, Doffinger, Rainer, Drewe, Elizabeth, Edgar, David, Egner, William, Ghurye, Rohit, Gilmour, Kimberley, Goddard, Sarah, Gordins, Pavel, Grigoriadou, Sofia, Hackett, Scott, Hague, Rosie, Hayman, Grant, Herwadkar, Archana, Huissoon, Aarnoud, Jolles, Stephen, Kelleher, Peter, Kumararatne, Dinakantha, Lear, Sara, Longhurst, Hilary, Lorenzo, Lorena, Maimaris, Jesmeen, Manson, Ania, McDermott, Elizabeth, Murng, Sai, Nejentsev, Sergey, Noorani, Sadia, Oksenhendler, Eric, Ponsford, Mark, Qasim, Waseem, Quinti, Isabella, Richter, Alex, Sargur, Ravishankar, Savic, Sinisa, Seneviratne, Suranjith, Sewell, Carrock, Stauss, Hans, Thomas, Moira, Welch, Steve, Willcocks, Lisa, Yeatman, Nigel, and Yong, Patrick

Abstract

Supplemental Digital Content is available in the text.

Published
2017
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63. Neuronal activity controls the antagonistic between PGC-1α and SMRT in regulating antioxidant defences

Author

Soriano Zaragoza, Francesc X. (Francesc Xavier), Léveillé, Frédéric, Papadia, Sofia, Bell, Karen F. S., Puddifoot, Clare, Hardingham, Giles E., and Universitat de Barcelona

Subjects
Neurons, Genetic regulation, Corea de Huntington, Malalties neurodegeneratives, Regulació genètica, Neurones, Neurodegenerative Diseases, Huntington's chorea
Abstract

Transcriptional coactivators and corepressors often have multiple targets and can have opposing actions on transcription and downstream physiological events. The coactivator peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α is under-expressed in Huntington's disease and is a regulator of antioxidant defenses and mitochondrial biogenesis. We show that in primary cortical neurons, expression of PGC-1α strongly promotes resistance to excitotoxic and oxidative stress in a cell autonomous manner, whereas knockdown increases sensitivity. In contrast, the transcriptional corepressor silencing mediator of retinoic acid and thyroid hormone receptors (SMRT) specifically antagonizes PGC-1α-mediated antioxidant effects. The antagonistic balance between PGC-1α and SMRT is upset in favor of PGC-1α by synaptic activity. Synaptic activity triggers nuclear export of SMRT reliant on multiple regions of the protein. Concommitantly, synaptic activity post-translationally enhances the transactivating potential of PGC-1α in a p38-dependent manner, as well as upregulating cyclic-AMP response element binding protein-dependent PGC-1α transcription. Activity-dependent targeting of PGC-1α results in enhanced gene expression mediated by the thyroid hormone receptor, a prototypical transcription factor coactivated by PGC-1α and repressed by SMRT. As a consequence of these events, SMRT is unable to antagonize PGC-1α-mediated resistance to oxidative stress in synaptically active neurons. Thus, PGC-1α and SMRT are antagonistic regulators of neuronal vulnerability to oxidative stress. Further, this coactivatorcorepressor antagonism is regulated by the activity status of the cell, with implications for neuronal viability.

Published
2010

65. A dominant gain-of-function mutation in universal tyrosine kinase SRC causes thrombocytopenia, myelofibrosis, bleeding, and bone pathologies.

Author

Turro, Ernest, Greene, Daniel, Wijgaerts, Anouck, Thys, Chantal, Lentaigne, Claire, Bariana, Tadbir K., Westbury, Sarah K., Kelly, Anne M., Selleslag, Dominik, Stephens, Jonathan C., Papadia, Sofia, Simeoni, Ilenia, Penkett, Christopher J., Ashford, Sofie, Attwood, Antony, Austin, Steve, Bakchoul, Tamam, Collins, Peter, Deevi, Sri V. V., and Favier, Rémi

Subjects
GENETIC mutation, PROTEIN-tyrosine kinases, MYELOFIBROSIS, THROMBOCYTOPENIA, HEMORRHAGE, ONTOLOGY
Abstract

The article discusses the study on a gain-of-function-mutation in universal tyrosine kinase SRC which causes bone pathologies, bleeding, myelofibrosis, and thrombocytopenia. The study reportedly involved genome sequencing and human phenotype ontology patient coding to identify the mutation. Also explored are the characteristics of the genetic defect.

Published
2016
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66. Expanded repertoire of RASGRP2variants responsible for platelet dysfunction and severe bleeding

Author

Westbury, Sarah K., Canault, Matthias, Greene, Daniel, Bermejo, Emilse, Hanlon, Katharine, Lambert, Michele P., Millar, Carolyn M., Nurden, Paquita, Obaji, Samya G., Revel-Vilk, Shoshana, Van Geet, Chris, Downes, Kate, Papadia, Sofia, Tuna, Salih, Watt, Christopher, Freson, Kathleen, Laffan, Michael A., Ouwehand, Willem H., Alessi, Marie-Christine, Turro, Ernest, and Mumford, Andrew D.

Abstract

Heritable platelet function disorders (PFDs) are genetically heterogeneous and poorly characterized. Pathogenic variants in RASGRP2, which encodes calcium and diacylglycerol-regulated guanine exchange factor I (CalDAG-GEFI), have been reported previously in 3 pedigrees with bleeding and reduced platelet aggregation responses. To better define the phenotype associated with pathogenic RASGRP2variants, we compared high-throughput sequencing and phenotype data from 2042 cases in pedigrees with unexplained bleeding or platelet disorders to data from 5422 controls. Eleven cases harbored 11 different, previously unreported RASGRP2variants that were biallelic and likely pathogenic. The variants included 5 high-impact variants predicted to prevent CalDAG-GEFI expression and 6 missense variants affecting the CalDAG-GEFI CDC25 domain, which mediates Rap1 activation during platelet inside-out αIIbβ3 signaling. Cases with biallelic RASGRP2variants had abnormal mucocutaneous, surgical, and dental bleeding from childhood, requiring ≥1 blood or platelet transfusion in 78% of cases. Platelets displayed reduced aggregation in response to adenosine 5′-diphosphate and epinephrine, but variable aggregation defects with other agonists. There were no other consistent clinical or laboratory features. These data enable definition of human CalDAG-GEFI deficiency as a nonsyndromic, recessive PFD associated with a moderate or severe bleeding phenotype and complex defects in platelet aggregation.

Published
2017
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70. Specific Targeting of Pro-Death NMDA Receptor Signals with Differing Reliance on the NR2B PDZ Ligand

Author

Soriano, Francesc X., primary, Martel, Marc-Andre, additional, Papadia, Sofia, additional, Vaslin, Anne, additional, Baxter, Paul, additional, Rickman, Colin, additional, Forder, Joan, additional, Tymianski, Michael, additional, Duncan, Rory, additional, Aarts, Michelle, additional, Clarke, Peter G. H., additional, Wyllie, David J. A., additional, and Hardingham, Giles E., additional

Published
2008
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71. Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses

Author

Papadia, Sofia, primary, Soriano, Francesc X, additional, Léveillé, Frédéric, additional, Martel, Marc-Andre, additional, Dakin, Kelly A, additional, Hansen, Henrik H, additional, Kaindl, Angela, additional, Sifringer, Marco, additional, Fowler, Jill, additional, Stefovska, Vanya, additional, Mckenzie, Grahame, additional, Craigon, Marie, additional, Corriveau, Roderick, additional, Ghazal, Peter, additional, Horsburgh, Karen, additional, Yankner, Bruce A, additional, Wyllie, David J A, additional, Ikonomidou, Chrysanthy, additional, and Hardingham, Giles E, additional

Published
2008
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73. Rare variants in GP1BBare responsible for autosomal dominant macrothrombocytopenia

Author

Sivapalaratnam, Suthesh, Westbury, Sarah K., Stephens, Jonathan C., Greene, Daniel, Downes, Kate, Kelly, Anne M., Lentaigne, Claire, Astle, William J., Huizinga, Eric G., Nurden, Paquita, Papadia, Sofia, Peerlinck, Kathelijne, Penkett, Christopher J., Perry, David J., Roughley, Catherine, Simeoni, Ilenia, Stirrups, Kathleen, Hart, Daniel P., Tait, R.Campbell, Mumford, Andrew D., Laffan, Michael A., Freson, Kathleen, Ouwehand, Willem H., Kunishima, Shinji, and Turro, Ernest

Abstract

The von Willebrand receptor complex, which is composed of the glycoproteins Ibα, Ibβ, GPV, and GPIX, plays an essential role in the earliest steps in hemostasis. During the last 4 decades, it has become apparent that loss of function of any 1 of 3 of the genes encoding these glycoproteins (namely, GP1BA, GP1BB, and GP9) leads to autosomal recessive macrothrombocytopenia complicated by bleeding. A small number of variants in GP1BAhave been reported to cause a milder and dominant form of macrothrombocytopenia, but only 2 tentative reports exist of such a variant in GP1BB. By analyzing data from a collection of more than 1000 genome-sequenced patients with a rare bleeding and/or platelet disorder, we have identified a significant association between rare monoallelic variants in GP1BBand macrothrombocytopenia. To strengthen our findings, we sought further cases in 2 additional collections in the United Kingdom and Japan. Across 18 families exhibiting phenotypes consistent with autosomal dominant inheritance of macrothrombocytopenia, we report on 27 affected cases carrying 1 of 9 rare variants in GP1BB.

Published
2017
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74. A gain-of-function variant in DIAPH1causes dominant macrothrombocytopenia and hearing loss

Author

Stritt, Simon, Nurden, Paquita, Turro, Ernest, Greene, Daniel, Jansen, Sjoert B., Westbury, Sarah K., Petersen, Romina, Astle, William J., Marlin, Sandrine, Bariana, Tadbir K., Kostadima, Myrto, Lentaigne, Claire, Maiwald, Stephanie, Papadia, Sofia, Kelly, Anne M., Stephens, Jonathan C., Penkett, Christopher J., Ashford, Sofie, Tuna, Salih, Austin, Steve, Bakchoul, Tamam, Collins, Peter, Favier, Rémi, Lambert, Michele P., Mathias, Mary, Millar, Carolyn M., Mapeta, Rutendo, Perry, David J., Schulman, Sol, Simeoni, Ilenia, Thys, Chantal, Gomez, Keith, Erber, Wendy N., Stirrups, Kathleen, Rendon, Augusto, Bradley, John R., van Geet, Chris, Raymond, F.Lucy, Laffan, Michael A., Nurden, Alan T., Nieswandt, Bernhard, Richardson, Sylvia, Freson, Kathleen, Ouwehand, Willem H., and Mumford, Andrew D.

Abstract

Macrothrombocytopenia (MTP) is a heterogeneous group of disorders characterized by enlarged and reduced numbers of circulating platelets, sometimes resulting in abnormal bleeding. In most MTP, this phenotype arises because of altered regulation of platelet formation from megakaryocytes (MKs). We report the identification of DIAPH1, which encodes the Rho-effector diaphanous-related formin 1 (DIAPH1), as a candidate gene for MTP using exome sequencing, ontological phenotyping, and similarity regression. We describe 2 unrelated pedigrees with MTP and sensorineural hearing loss that segregate with a DIAPH1R1213* variant predicting partial truncation of the DIAPH1 diaphanous autoregulatory domain. The R1213* variant was linked to reduced proplatelet formation from cultured MKs, cell clustering, and abnormal cortical filamentous actin. Similarly, in platelets, there was increased filamentous actin and stable microtubules, indicating constitutive activation of DIAPH1. Overexpression of DIAPH1 R1213* in cells reproduced the cytoskeletal alterations found in platelets. Our description of a novel disorder of platelet formation and hearing loss extends the repertoire of DIAPH1-related disease and provides new insight into the autoregulation of DIAPH1 activity.

Published
2016
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75. Suppression of the Intrinsic Apoptosis Pathway by Synaptic Activity.

Author

Léveillé, Frédéric, Papadia, Sofia, Fricker, Michael, Bell, Karen F. S., Soriano, Francesc X., Martel, Marc-André, Puddifoot, Clare, Habel, Marlen, Wyllie, David J., Ikonomidou, Chrysanthy, Tolkovsky, Aviva M., and Hardingham, Giles E.

Subjects
*CELL death, *GENE expression, *GENETIC regulation, *NEURONS, *CYTOCHROMES
Abstract

Synaptic activity promotes resistance to diverse apoptotic insults, the mechanism behind which is incompletely understood. We show here that a coordinated downregulation of core components of the intrinsic apoptosis pathway by neuronal activity forms a key part of the underlying mechanism. Activity-dependent protection against apoptotic insults is associated with inhibition of cytochrome c release in most but not all neurons, indicative of anti-apoptotic signaling both upstream and downstream of this step.Wefind that enhanced firing activity suppresses expression of the proapoptotic BH3-only member gene Puma in a NMDA receptor-dependent, p53-independent manner. Puma expression is sufficient to induce cytochrome c loss and neuronal apoptosis. Puma deficiency protects neurons against apoptosis and also occludes the protective effect of synaptic activity, while blockade of physiological NMDA receptor activity in the developing mouse brain induces neuronal apoptosis that is preceded by upregulation of Puma. However, enhanced activity can also confer resistance to Puma-induced apoptosis, acting downstream of cytochrome c release. This mechanism is mediated by transcriptional suppression of apoptosome components Apaf-1 and procaspase-9, and limiting caspase-9 activity, since overexpression of procaspase-9 accelerates the rate of apoptosis in active neurons back to control levels. Synaptic activity does not exert further significant anti-apoptotic effects downstream of caspase-9 activation, since an inducible form of caspase-9 overrides the protective effect of synaptic activity, despite activity-induced transcriptional suppression of caspase-3. Thus, suppression of apoptotic gene expression may synergize with other activity-dependent events such as enhancement of antioxidant defenses to promote neuronal survival. [ABSTRACT FROM AUTHOR]

Published
2010
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76. Preconditioning Doses of NMDA Promote Neuroprotection by Enhancing Neuronal Excitability.

Author

Soriano, Francesc X., Papadia, Sofia, Hofmann, Frank, Hardingham, Neil R., Bading, Hilmar, and Hardingham, Giles E.

Subjects
*NEURAL receptors, *METHYL aspartate, *APOPTOSIS, *CELL death, *GLYCOGEN
Abstract

Neuroprotection can be induced by low doses of NMDA, which activate both synaptic and extrasynaptic NMDA receptors. This is in apparent contradiction with our recent findings that extrasynaptic NMDA receptor signaling exerts a dominant inhibitory effect on prosurvival signaling from synaptic NMDA receptors. Here we report that exposure to low preconditioning doses of NMDA results in preferential activation of synaptic NMDA receptors because of a dramatic increase in action potential firing. Both acute and long-lasting phases of neuroprotection in the face of apoptotic or excitotoxic insults are dependent on this firing enhancement. Key mediators of synaptic NMDA receptor-dependent neuroprotection, phosphatidylinositol 3 kinase-Akt (PI3 kinase-Akt) signaling to Forkhead box subgroup O (FOXO) export and glycogen synthase kinase 3β (GSK3β) inhibition and cAMP response element-binding protein-dependent (CREB-dependent) activation of brain-derived neurotrophic factor (BDNF), can be induced only by low doses of NMDA via this action potential-dependent route. In contrast, NMDA doses on the other side of the toxicity threshold do not favor synaptic NMDA receptor activation because they strongly suppress firing rates below baseline. The classic bell-shaped curve depicting neuronal fate in response to NMDA dose can be viewed as the net effect of two antagonizing (synaptic vs extrasynaptic) curves: via increased firing the synaptic signaling dominates at low doses, whereas firing becomes suppressed and extrasynaptic signaling dominates as the toxicity threshold is crossed. [ABSTRACT FROM AUTHOR]

Published
2006
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77. Nuclear Ca2+ and the cAMP Response Element-Binding Protein Family Mediate a Late Phase of Activity-Dependent Neuroprotection.

Author

Papadia, Sofia, Stevenson, Patrick, Hardingham, Neil R., Bading, Hilmar, and Hardingham, Giles E.

Subjects
*CALCIUM, *NERVE tissue proteins, *APOPTOSIS, *METHYL aspartate, *GENE expression, *TRANSCRIPTION factors
Abstract

The mechanism by which physiological synaptic NMDA receptor activity promotes neuronal survival is not well understood. Here, we show that that an episode of synaptic activity can promote neuroprotection for a long time after that activity has ceased. This long-lasting or "late phase" of neuroprotection is dependent on nuclear calcium signaling and cAMP response element (CRE)-mediated gene expression. In contrast, neuroprotection evoked acutely by ongoing synaptic activity relies solely on the activation of the phosphatidylinositol 3-kinase/Akt pathway. This "acute phase" does not require nuclear calcium signaling and is independent of activation of the CRE-binding protein (CREB) family of transcription factors. Thus, activity-dependent neuroprotection comprises two mechanistically distinct phases that differ in their spatial requirements for calcium and in their reliance on the CREB family. [ABSTRACT FROM AUTHOR]

Published
2005
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78. Nuclear Ca2+ and CaM kinase IV specify hormonal- and Notch-responsiveness.

Author

Mckenzie, Grahame J., Stevenson, Patrick, Ward, George, Papadia, Sofia, Bading, Hilmar, Chawla, Sangeeta, Privalsky, Martin, and Hardingham, Giles E.

Subjects
PROTEIN kinases, NEURONS, CALCIUM, MITOGENS, TRANSCRIPTION factors, HISTONE deacetylase, NEUROCHEMISTRY
Abstract

Many neuronal processes require gene activation by synaptically evoked Ca2+ transients. Ca2+-dependent signal pathways activate some transcription factors outright, but here we report that such signals also potentiate the activation of nuclear receptors by their cognate hormone, and of CBF1 by Notch, transcription factors hitherto not thought to be Ca2+-responsive. This potentiation is occluded by histone deacetylase inhibition, indicating a mechanism involving inactivation of co-repressors associated with these transcription factors. Synaptic activity, acting via the nuclear Ca2+-dependent activation of CaM kinase IV, triggers the disruption of subnuclear domains containing class II histone deacetylases (HDACs) and silencing mediator of retinoic acid and thyroid hormone receptors (SMRT), a broad-specificity co-repressor which represses nuclear hormone receptors and CBF1. The sequential loss of class II HDACs and SMRT from the subnuclear domains, followed by nuclear export, is associated with disruption of SMRT interaction with its target transcription factors and sensitization of these factors to their activating signal. Counterbalancing these changes, protein phosphatase 1 promotes nuclear localization of SMRT and inactivation of nuclear receptors and CBF1. Thus, the synaptically controlled kinase-phosphatase balance of the neuron determines the efficacy of SMRT-mediated repression and the signal-responsiveness of a variety of transcription factors. [ABSTRACT FROM AUTHOR]

Published
2005
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79. Expanded repertoire of RASGRP2 variants responsible for platelet dysfunction and severe bleeding

Author

Westbury, Sarah K, Canault, Matthias, Greene, Daniel, Bermejo, Emilse, Hanlon, Katharine, Lambert, Michele P, Millar, Carolyn M, Nurden, Paquita, Obaji, Samya G, Revel-Vilk, Shoshana, Van Geet, Chris, Downes, Kate, Papadia, Sofia, Tuna, Salih, Watt, Christopher, NIHR BioResource–Rare Diseases Consortium, Freson, Kathleen, Laffan, Michael A, Ouwehand, Willem H, Alessi, Marie-Christine, Turro, Ernest, and Mumford, Andrew D

Subjects
Blood Platelets, Male, Base Sequence, Mutation, Guanine Nucleotide Exchange Factors, Humans, Female, Hemorrhage, Alleles, 3. Good health, Pedigree
Abstract

Heritable platelet function disorders (PFDs) are genetically heterogeneous and poorly characterized. Pathogenic variants in RASGRP2, which encodes calcium and diacylglycerol-regulated guanine exchange factor I (CalDAG-GEFI), have been reported previously in 3 pedigrees with bleeding and reduced platelet aggregation responses. To better define the phenotype associated with pathogenic RASGRP2 variants, we compared high-throughput sequencing and phenotype data from 2042 cases in pedigrees with unexplained bleeding or platelet disorders to data from 5422 controls. Eleven cases harbored 11 different, previously unreported RASGRP2 variants that were biallelic and likely pathogenic. The variants included 5 high-impact variants predicted to prevent CalDAG-GEFI expression and 6 missense variants affecting the CalDAG-GEFI CDC25 domain, which mediates Rap1 activation during platelet inside-out αIIbβ3 signaling. Cases with biallelic RASGRP2 variants had abnormal mucocutaneous, surgical, and dental bleeding from childhood, requiring ≥1 blood or platelet transfusion in 78% of cases. Platelets displayed reduced aggregation in response to adenosine 5'-diphosphate and epinephrine, but variable aggregation defects with other agonists. There were no other consistent clinical or laboratory features. These data enable definition of human CalDAG-GEFI deficiency as a nonsyndromic, recessive PFD associated with a moderate or severe bleeding phenotype and complex defects in platelet aggregation.

80. A dominant gain-of-function mutation in universal tyrosine kinase SRCcauses thrombocytopenia, myelofibrosis, bleeding, and bone pathologies

Author

Turro, Ernest, Greene, Daniel, Wijgaerts, Anouck, Thys, Chantal, Lentaigne, Claire, Bariana, Tadbir K., Westbury, Sarah K., Kelly, Anne M., Selleslag, Dominik, Stephens, Jonathan C., Papadia, Sofia, Simeoni, Ilenia, Penkett, Christopher J., Ashford, Sofie, Attwood, Antony, Austin, Steve, Bakchoul, Tamam, Collins, Peter, Deevi, Sri V. V., Favier, Rémi, Kostadima, Myrto, Lambert, Michele P., Mathias, Mary, Millar, Carolyn M., Peerlinck, Kathelijne, Perry, David J., Schulman, Sol, Whitehorn, Deborah, Wittevrongel, Christine, De Maeyer, Marc, Rendon, Augusto, Gomez, Keith, Erber, Wendy N., Mumford, Andrew D., Nurden, Paquita, Stirrups, Kathleen, Bradley, John R., Lucy Raymond, F., Laffan, Michael A., Van Geet, Chris, Richardson, Sylvia, Freson, Kathleen, and Ouwehand, Willem H.

Abstract

E527K hyperactive SRC results in megakaryocytes with increased podosome formation, thrombocytopenia, myelofibrosis, bleeding, and bone pathologies.

Published
2016
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81. Sphingolipid dysregulation due to lack of functional KDSR impairs proplatelet formation causing thrombocytopenia

Author

Deborah Whitehorn, Mattia Frontini, Ernest Turro, Luigi Grassi, Cedric Ghevaert, Albert Koulman, Tadbir K. Bariana, Veerle Labarque, Keith Gomez, Willem H. Ouwehand, Benjamin Jenkins, Jessica Heremans, Olga Shamardina, Mara De Reys, Chris Van Geet, Sofia Papadia, Denis Seyres, Frances Burden, Daniel Greene, Nihr BioResource, Chantal Thys, Kathleen Freson, Seyres, Denis [0000-0002-2066-6980], Shamardina, Olga [0000-0003-4994-2157], Papadia, Sofia [0000-0002-9222-3812], Koulman, Albert [0000-0001-9998-051X], Ouwehand, Willem [0000-0002-7744-1790], Ghevaert, Cedric [0000-0002-9251-0934], Frontini, Mattia [0000-0001-8074-6299], Turro Bassols, Ernest [0000-0002-1820-6563], and Apollo - University of Cambridge Repository

Subjects
Platelets, Blood Platelets, Male, induced pluripotent stem cell, Ceramide, Cellular differentiation, Induced Pluripotent Stem Cells, Biology, Article, megakaryocyte, Platelet Biology & its Disorders, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Erythrokeratodermia variabilis, Megakaryocyte, medicine, Animals, Humans, Metabolomics, Myelofibrosis, Induced pluripotent stem cell, Child, Cells, Cultured, Zebrafish, Sphingolipids, proplatelet, Cell Differentiation, Hematology, medicine.disease, Prognosis, Sphingolipid, Thrombocytopenia, Pedigree, Alcohol Oxidoreductases, medicine.anatomical_structure, chemistry, Mutation, Cancer research, Female, sphingolipid, Stem cell, Megakaryocytes, 030215 immunology
Abstract

Sphingolipids are fundamental to membrane trafficking, apoptosis, and cell differentiation and proliferation. KDSR or 3-keto-dihydrosphingosine reductase is an essential enzyme for de novo sphingolipid synthesis, and pathogenic mutations in KDSR result in the severe skin disorder erythrokeratodermia variabilis et progressiva-4 Four of the eight reported cases also had thrombocytopenia but the underlying mechanism has remained unexplored. Here we expand upon the phenotypic spectrum of KDSR deficiency with studies in two siblings with novel compound heterozygous variants associated with thrombocytopenia, anemia, and minimal skin involvement. We report a novel phenotype of progressive juvenile myelofibrosis in the propositus, with spontaneous recovery of anemia and thrombocytopenia in the first decade of life. Examination of bone marrow biopsies showed megakaryocyte hyperproliferation and dysplasia. Megakaryocytes obtained by culture of CD34+ stem cells confirmed hyperproliferation and showed reduced proplatelet formation. The effect of KDSR insufficiency on the sphingolipid profile was unknown, and was explored in vivo and in vitro by a broad metabolomics screen that indicated activation of an in vivo compensatory pathway that leads to normalization of downstream metabolites such as ceramide. Differentiation of propositus-derived induced pluripotent stem cells to megakaryocytes followed by expression of functional KDSR showed correction of the aberrant cellular and biochemical phenotypes, corroborating the critical role of KDSR in proplatelet formation. Finally, Kdsr depletion in zebrafish recapitulated the thrombocytopenia and showed biochemical changes similar to those observed in the affected siblings. These studies support an important role for sphingolipids as regulators of cytoskeletal organization during megakaryopoiesis and proplatelet formation. ispartof: HAEMATOLOGICA vol:104 issue:5 pages:1036-1045 ispartof: location:Italy status: published

Published
2019

82. Expanded repertoire of RASGRP2 variants responsible for platelet dysfunction and severe bleeding

Author

Emilse Bermejo, Michele P. Lambert, Chris Van Geet, Samya Obaji, Marie-Christine Alessi, Sofia Papadia, Matthias Canault, Shoshana Revel-Vilk, Daniel Greene, Andrew D Mumford, Ernest Turro, Salih Tuna, Sarah K Westbury, Kate Downes, Willem H. Ouwehand, Carolyn M. Millar, Christopher Watt, Kathleen Freson, Katharine Hanlon, Paquita Nurden, Michael Laffan, Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistics Unit, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Hematological Research Institute, National Academy of Medicine, Department of Haematology [Glasgow Royal Infirmary], University of Glasgow-Glasgow Royal Infirmary, Institut Parisien de Recherche Architecture Urbanistique Société (IPRAUS), Architecture Urbanisme Société : Savoir Enseignement Recherche (UMR AUSser), Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture et de la Communication (MCC)-École nationale supérieure d'architecture de Paris-Belleville (ENSA PB)-École nationale supérieure d'architecture de Paris-La Villette (ENSAPLV)-École nationale supérieure d'architecture de Paris-Malaquais (ENSAPM)-École Nationale Supérieure d'Architecture de la Ville et des Territoires à Marne-la-Vallée (éavt&t)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture et de la Communication (MCC)-École nationale supérieure d'architecture de Paris-Belleville (ENSA PB)-École nationale supérieure d'architecture de Paris-La Villette (ENSAPLV)-École nationale supérieure d'architecture de Paris-Malaquais (ENSAPM)-École Nationale Supérieure d'Architecture de la Ville et des Territoires à Marne-la-Vallée (éavt&t), IHU-LIRYC, CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Pediatric Hematology/Oncology Department, Hadassah Hebrew University Medical Center [Jerusalem], Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, Université Catholique de Louvain = Catholic University of Louvain (UCL), NIHR BioResource - Rare Diseases, Cambridge University Hospitals (CUH), Department of Haematology, Queens Elizabeth Hospital [Birmingham], NHS Blood and Transplant, Center for Molecular and Vascular Biology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Cambridge [UK] (CAM), The Wellcome Trust Sanger Institute [Cambridge], Nutrition, obésité et risque thrombotique ( NORT ), Institut National de la Recherche Agronomique ( INRA ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CRLCC Antoine Lacassagne, Institut Parisien de Recherche Architecture Urbanistique Société ( IPRAUS ), Architecture Urbanisme Société : Savoir Enseignement Recherche ( UMR AUSser ), École nationale supérieure d'architecture de Paris-La Villette ( ENSAPLV ) -École nationale supérieure d'architecture de Paris-Belleville ( ENSA PB ) -Ministère de la Culture et de la Communication ( MCC ) -École nationale supérieure d'architecture de Paris-Malaquais ( ENSAPM ) -Centre National de la Recherche Scientifique ( CNRS ) -École nationale supérieure d'architecture de Paris-La Villette ( ENSAPLV ) -École nationale supérieure d'architecture de Paris-Belleville ( ENSA PB ) -Ministère de la Culture et de la Communication ( MCC ) -École nationale supérieure d'architecture de Paris-Malaquais ( ENSAPM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Université Catholique de Louvain, Cambridge University Hospitals ( CUH ), Queen Elizabeth Hospital, Catholic University of Leuven ( KU Leuven ), University of Cambridge [UK] ( CAM ), Medical Research Council (MRC), Downes, Kate [0000-0003-0366-1579], Papadia, Sofia [0000-0002-9222-3812], Tuna, Salih [0000-0003-3606-4367], Ouwehand, Willem [0000-0002-7744-1790], Turro Bassols, Ernest [0000-0002-1820-6563], Apollo - University of Cambridge Repository, École nationale supérieure d'architecture de Paris-La Villette (ENSAPLV), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-École nationale supérieure d'architecture de Paris-Belleville (ENSA PB)-Ministère de la Culture et de la Communication (MCC)-École nationale supérieure d'architecture de Paris-Malaquais (ENSAPM)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Architecture de la Ville et des Territoires à Marne-la-Vallée (éavt&t)-École nationale supérieure d'architecture de Paris-La Villette (ENSAPLV), and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-École nationale supérieure d'architecture de Paris-Belleville (ENSA PB)-Ministère de la Culture et de la Communication (MCC)-École nationale supérieure d'architecture de Paris-Malaquais (ENSAPM)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Architecture de la Ville et des Territoires à Marne-la-Vallée (éavt&t)

Subjects
Male, 0301 basic medicine, genetic disorde, 030204 cardiovascular system & hematology, Bioinformatics, Biochemistry, ACTIVATION, 0302 clinical medicine, ISTH, GENETIC-VARIANTS, [SDV.IDA]Life Sciences [q-bio]/Food engineering, 1114 Paediatrics And Reproductive Medicine, Guanine Nucleotide Exchange Factors, Missense mutation, Platelet, WORLDWIDE SURVEY, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, ComputingMilieux_MISCELLANEOUS, Blood Platelet Disorders, Hematology, [ SDV.IDA ] Life Sciences [q-bio]/Food engineering, DEFECTS, Phenotype, trouble génétiq, Pedigree, 3. Good health, phénotype, thrombocytopath, Female, Life Sciences & Biomedicine, Blood Platelets, medicine.medical_specialty, DISORDERS, NIHR BioResource–Rare Diseases Consortium, Platelet disorder, Immunology, Hemorrhage, DIAGNOSIS, 1102 Cardiovascular Medicine And Haematology, 03 medical and health sciences, Internal medicine, Journal Article, medicine, Humans, Alleles, Science & Technology, Base Sequence, MUTATIONS, business.industry, Genetic heterogeneity, THROMBOCYTOPENIA, séquençage à ha, 1103 Clinical Sciences, Cell Biology, activation plaq, 030104 developmental biology, Platelet transfusion, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, CALDAG-GEFI, business
Abstract

International audience; Heritable platelet function disorders (PFDs) are genetically heterogeneous and poorly characterised. Pathogenic variants in RASGRP2, which encodes calcium and diacylglycerol-regulated guanine exchange factor I (CalDAG-GEFI), have been reported previously in three pedigrees with bleeding and reduced platelet aggregation responses. To better define the phenotype associated with pathogenic RASGRP2 variants, we compared high-throughput sequencing and phenotype data from 2,042 cases in pedigrees with unexplained bleeding or platelet disorders to data from 5,422 controls. Eleven cases harboured 11 different, previously unreported RASGRP2 variants that were biallelic and likely pathogenic. The variants included five high-impact variants predicted to prevent CalDAG-GEFI expression and six missense variants affecting the CalDAG-GEFI CDC25 domain, which mediates Rap1 activation during platelet inside-out αIIbβ3 signalling. Cases with biallelic RASGRP2 variants had abnormal mucocutaneous, surgical and dental bleeding from childhood, requiring at least one blood or platelet transfusion in 78% of cases. Platelets displayed reduced aggregation in response to ADP and epinephrine, but variable aggregation defects with other agonists. There were no other consistent clinical or laboratory features. These data enable definition of human CalDAG-GEFI deficiency as a non-syndromic, recessive PFD associated with a moderate or severe bleeding phenotype and complex defects in platelet aggregation.

Published
2017
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83. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

Author

Hendricks, AE, Bochukova, EG, Marenne, G, Keogh, JM, Atanassova, N, Bounds, R, Wheeler, E, Mistry, V, Henning, E, Körner, A, Muddyman, D, McCarthy, S, Hinney, A, Hebebrand, J, Scott, RA, Langenberg, C, Wareham, NJ, Surendran, P, Howson, JM, Butterworth, AS, Danesh, J, Nordestgaard, BG, Nielsen, SF, Afzal, S, Papadia, S, Ashford, S, Garg, S, Millhauser, GL, Palomino, RI, Kwasniewska, A, Tachmazidou, I, O'Rahilly, S, Zeggini, E, Barroso, I, Farooqi, IS, Group, Understanding Society Scientific, Consortium, Epic-Cvd, Consortium, Uk10K, Keogh, Julia [0000-0002-0399-4114], Wheeler, Eleanor [0000-0002-8616-6444], Henning, Elana [0000-0002-0399-4114], McCarthy, Shane [0000-0002-2715-4187], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Surendran, Praveen [0000-0002-4911-6077], Howson, Joanna [0000-0001-7618-0050], Butterworth, Adam [0000-0002-6915-9015], Danesh, John [0000-0003-1158-6791], Papadia, Sofia [0000-0002-9222-3812], O'Rahilly, Stephen [0000-0003-2199-4449], Barroso, Ines [0000-0001-5800-4520], Farooqi, Ismaa [0000-0001-7609-3504], and Apollo - University of Cambridge Repository

Subjects
Male, Models, Molecular, Pediatric Obesity, Understanding Society Scientific Group, Protein Conformation, Science, Rodentia, Article, EPIC-CVD Consortium, Mice, Chromogranins, GTP-Binding Protein alpha Subunits, Gs, Odds Ratio, Animals, Humans, UK10K Consortium, Genetic Predisposition to Disease, Genetic Association Studies, Genetic Variation, Obesity, Morbid, Pedigree, Case-Control Studies, Mutation, Medicine, Female
Abstract

Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF~0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10−3), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies.

Published
2017

84. Rare variants in $\textit{GP1BB}$ are responsible for autosomal dominant macrothrombocytopenia

Author

Sivapalaratnam, S, Westbury, SK, Stephens, JC, Greene, D, Downes, K, Kelly, AM, Lentaigne, C, Astle, WJ, Huizinga, EG, Nurden, P, Papadia, S, Peerlinck, K, Penkett, CJ, Perry, DJ, Roughley, C, Simeoni, I, Stirrups, K, Hart, DP, Tait, RC, Mumford, AD, NIHR BioResource, Laffan, MA, Freson, K, Ouwehand, WH, Kunishima, S, Turro, E, Stephens, Jonathan [0000-0003-2020-9330], Downes, Kate [0000-0003-0366-1579], Astle, William [0000-0001-8866-6672], Papadia, Sofia [0000-0002-9222-3812], Simeoni, Ilenia [0000-0001-5039-2194], Johnson, Kathleen [0000-0002-6823-3252], Ouwehand, Willem [0000-0002-7744-1790], Turro Bassols, Ernest [0000-0002-1820-6563], and Apollo - University of Cambridge Repository

Subjects
Blood Platelets, Male, Genome, Human, Platelet Count, Gene Expression, High-Throughput Nucleotide Sequencing, Hemorrhage, Thrombocytopenia, Pedigree, Platelet Glycoprotein GPIb-IX Complex, Case-Control Studies, Mutation, Humans, Female, Alleles, Genes, Dominant
Abstract

The von Willebrand receptor complex, which is composed of the glycoproteins Ibα, Ibβ, GPV, and GPIX, plays an essential role in the earliest steps in hemostasis. During the last 4 decades, it has become apparent that loss of function of any 1 of 3 of the genes encoding these glycoproteins (namely, $\textit{GP1BBA}$, $\textit{GP1BB}$, and $\textit{GP9}$) leads to autosomal recessive macrothrombocytopenia complicated by bleeding. A small number of variants in $\textit{GP1BA}$ have been reported to cause a milder and dominant form of macrothrombocytopenia, but only 2 tentative reports exist of such a variant in $\textit{GP1BB}$ By analyzing data from a collection of more than 1000 genome-sequenced patients with a rare bleeding and/or platelet disorder, we have identified a significant association between rare monoallelic variants in $\textit{GP1BB}$ and macrothrombocytopenia. To strengthen our findings, we sought further cases in 2 additional collections in the United Kingdom and Japan. Across 18 families exhibiting phenotypes consistent with autosomal dominant inheritance of macrothrombocytopenia, we report on 27 affected cases carrying 1 of 9 rare variants in $\textit{GP1BB}$.

Published
2017

85. A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders

Author

Sol Schulman, Daniel J. Hampshire, Jennifer Jolley, Peter A. Smethurst, Willem H. Ouwehand, Alan T. Nurden, Ilenia Simeoni, William Stevenson, Paolo Gresele, Ri Liesner, Kathleen Freson, Christel Van Geet, Walter H. A. Kahr, Tadbir K. Bariana, Paquita Nurden, Minka J A Vries, David A. Wilcox, Mary Mathias, Fengyuan Hu, Maha Othman, Marguerite Neerman-Arbez, Pawan Poudel, Matthias Ballmaier, Pieter H. Reitsma, Peter William Collins, Jose A. Lopez, Artur J. Szkotak, Jose A. Guerrero, Marie-Christine Alessi, Manuela Germeshausen, Jonathan Stephens, Cedric Ghevaert, Michael Gattens, Carolyn M. Millar, Gareth Baynam, Marian Hill, Marco Cattaneo, Antony P. Attwood, Shoshana Revel-Vilk, Matthew T. Rondina, Anne M. Kelly, Sri V V Deevi, Sofia Papadia, Amit C. Nathwani, Paul F. Bray, Daniel B. Bellissimo, Michael Laffan, Deborah L. French, Daniel P. Hart, Shinji Kunishima, Bin Zhang, Rutendo Mapeta, Salih Tuna, Anne Goodeve, Keith Gomez, Nancy Hogg, Ernest Turro, Johan W. M. Heemskerk, Marta Bertoli, Karyn Megy, Ron Kerr, Christopher J. Penkett, David J. Perry, Claire Lentaigne, Deborah Whitehorn, Daniel Greene, Suthesh Sivapalaratnam, Myrto Kostadima, Andrew D Mumford, Bruce Furie, Emilse Bermejo, Rémi Favier, Michele P. Lambert, Louise C. Daugherty, Yvonne M. C. Henskens, Augusto Rendon, Loredana Bury, Kathelijne Peerlinck, Sarah K Westbury, Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical Research Council (MRC), Simeoni, Ilenia [0000-0001-5039-2194], Stephens, Jonathan [0000-0003-2020-9330], Megy, Karyn [0000-0002-2826-3879], Papadia, Sofia [0000-0002-9222-3812], Ghevaert, Cedric [0000-0002-9251-0934], Tuna, Salih [0000-0003-3606-4367], Rendon Restrepo, Augusto [0000-0001-8994-0039], Ouwehand, Willem [0000-0002-7744-1790], Turro Bassols, Ernest [0000-0002-1820-6563], Apollo - University of Cambridge Repository, Biochemie, RS: CARIM - R1.04 - Clinical thrombosis and haemostasis, Promovendi CD, RS: CARIM - R1.03 - Cell biochemistry of thrombosis and haemostasis, Medische Microbiologie, and MUMC+: DA CDL Algemeen (9)

Subjects
Male, 0301 basic medicine, 030204 cardiovascular system & hematology, Bioinformatics, Biochemistry, thrombotic, 0302 clinical medicine, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Copy-number variation, 1102 Cardiorespiratory Medicine and Haematology, UNITED-KINGDOM, POPULATION, Blood Platelet Disorders, education.field_of_study, Hematology, High-Throughput Nucleotide Sequencing, 3. Good health, GENOME, Female, Developed a targeted sequencing platform covering 63 genes linked to heritable bleeding, Life Sciences & Biomedicine, and platelet disorders. The ThromboGenomics platform provides a sensitive genetic test to obtain molecular diagnoses in patients with a suspected etiology, VON-WILLEBRAND-DISEASE, medicine.medical_specialty, DNA Copy Number Variations, Platelet disorder, Immunology, Population, FACTOR-VIII GENE, Hemorrhage, WISKOTT-ALDRICH SYNDROME, Polymorphism, Single Nucleotide, 03 medical and health sciences, Internal medicine, MANAGEMENT, LINKAGE, Von Willebrand disease, medicine, Humans, Genetic Predisposition to Disease, education, POLYMORPHISMS, Genetic Association Studies, Science & Technology, MUTATIONS, business.industry, Case-control study, 1103 Clinical Sciences, Thrombosis, Sequence Analysis, DNA, Cell Biology, medicine.disease, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Case-Control Studies, Mutation, Etiology, 1114 Paediatrics and Reproductive Medicine, business, Developed a targeted sequencing platform covering 63 genes linked to heritable bleeding, thrombotic, and platelet disorders. The ThromboGenomics platform provides a sensitive genetic test to obtain molecular diagnoses in patients with a suspected etiology
Abstract

Inherited bleeding, thrombotic and platelet disorders (BPDs) are diseases affecting approximately 300 individuals per million births. With the exception of haemophilia and von Willebrand disease patients, a molecular analysis for patients with a BPD is often unavailable. Many specialised tests are usually required to reach a putative diagnosis and they are typically performed in a step-wise manner to control costs. This approach causes delays and a conclusive molecular diagnosis is often never reached which can compromise treatment and impede rapid identification of affected relatives. To address this unmet diagnostic need, we designed a high-throughput sequencing (HTS) platform targeting 63 genes relevant for BPDs. The platform can call single nucleotide variants (SNVs), short insertions/deletions (indels) and large copy number variants (CNVs), though not inversions, which are subjected to automated filtering for diagnostic prioritization, resulting in an average of 5.34 candidate variants per individual. We sequenced 159 and 137 samples respectively from cases with and without previously known causal variants. Among the latter group, 61 cases had clinical and laboratory phenotypes indicative of a particular molecular etiology while the remainder had ana priorihighly uncertain etiology. All previously detected variants were recapitulated and, when the etiology was suspected but unknown or uncertain, a molecular diagnosis was reached in 56 of 61 and only eight of 76 cases, respectively. The latter category highlights the need for further research into novel causes of BPDs. The ThromboGenomics platform thus provides an affordable DNA-based test to diagnose patients suspected of having a known inherited BPD.

Published
2016
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86. SynGAP isoforms exert opposing effects on synaptic strength

Author

Aoife McMahon, Jyoti S. Choudhary, Mark W. Barnett, Giles E. Hardingham, Noboru H. Komiyama, Timothy O'Leary, Sofia Papadia, Peter C. Kind, David J. A. Wyllie, P N Stoney, Mark O. Collins, Seth G. N. Grant, O'Leary, Timothy [0000-0002-1029-0158], Papadia, Sofia [0000-0002-9222-3812], and Apollo - University of Cambridge Repository

Subjects
Gene isoform, Chemistry(all), Molecular Sequence Data, General Physics and Astronomy, Physics and Astronomy(all), Biology, SYNGAP1, Hippocampus, Mass Spectrometry, Article, General Biochemistry, Genetics and Molecular Biology, Primer extension, Mice, 03 medical and health sciences, 0302 clinical medicine, Rapid amplification of cDNA ends, Animals, Protein Isoforms, Amino Acid Sequence, Peptide sequence, 030304 developmental biology, Neurons, Genetics, 0303 health sciences, Multidisciplinary, Biochemistry, Genetics and Molecular Biology(all), Alternative splicing, General Chemistry, Cell biology, Electrophysiology, Mice, Inbred C57BL, ras GTPase-Activating Proteins, Synapses, Synaptic plasticity, Excitatory postsynaptic potential, 030217 neurology & neurosurgery
Abstract

Alternative promoter usage and alternative splicing enable diversification of the transcriptome. Here we demonstrate that the function of Synaptic GTPase-Activating Protein (SynGAP), a key synaptic protein, is determined by the combination of its amino-terminal sequence with its carboxy-terminal sequence. 5′ rapid amplification of cDNA ends and primer extension show that different N-terminal protein sequences arise through alternative promoter usage that are regulated by synaptic activity and postnatal age. Heterogeneity in C-terminal protein sequence arises through alternative splicing. Overexpression of SynGAP α1 versus α2 C-termini-containing proteins in hippocampal neurons has opposing effects on synaptic strength, decreasing and increasing miniature excitatory synaptic currents amplitude/frequency, respectively. The magnitude of this C-terminal-dependent effect is modulated by the N-terminal peptide sequence. This is the first demonstration that activity-dependent alternative promoter usage can change the function of a synaptic protein at excitatory synapses. Furthermore, the direction and degree of synaptic modulation exerted by different protein isoforms from a single gene locus is dependent on the combination of differential promoter usage and alternative splicing., Synaptic GTPase-activating protein, SynGAP, is a postsynaptic signalling protein that can regulate synaptic function. McMahon et al. express different SynGAP isoforms in neurons and find that the effect on synaptic strength depends on alternative promoter usage and alternative splicing of the C-terminus.

Published
2012
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87. Sphingolipid dysregulation due to lack of functional KDSR impairs proplatelet formation causing thrombocytopenia.

Author

Bariana TK, Labarque V, Heremans J, Thys C, De Reys M, Greene D, Jenkins B, Grassi L, Seyres D, Burden F, Whitehorn D, Shamardina O, Papadia S, Gomez K, BioResource N, Van Geet C, Koulman A, Ouwehand WH, Ghevaert C, Frontini M, Turro E, and Freson K

Subjects
Alcohol Oxidoreductases genetics, Animals, Blood Platelets metabolism, Cell Differentiation, Cells, Cultured, Child, Female, Humans, Induced Pluripotent Stem Cells metabolism, Male, Megakaryocytes metabolism, Metabolomics, Mutation, Pedigree, Prognosis, Thrombocytopenia metabolism, Thrombocytopenia pathology, Zebrafish, Alcohol Oxidoreductases deficiency, Blood Platelets pathology, Induced Pluripotent Stem Cells pathology, Megakaryocytes pathology, Sphingolipids metabolism, Thrombocytopenia etiology
Abstract

Sphingolipids are fundamental to membrane trafficking, apoptosis, and cell differentiation and proliferation. KDSR or 3-keto-dihydrosphingosine reductase is an essential enzyme for de novo sphingolipid synthesis, and pathogenic mutations in KDSR result in the severe skin disorder erythrokeratodermia variabilis et progressiva-4 Four of the eight reported cases also had thrombocytopenia but the underlying mechanism has remained unexplored. Here we expand upon the phenotypic spectrum of KDSR deficiency with studies in two siblings with novel compound heterozygous variants associated with thrombocytopenia, anemia, and minimal skin involvement. We report a novel phenotype of progressive juvenile myelofibrosis in the propositus, with spontaneous recovery of anemia and thrombocytopenia in the first decade of life. Examination of bone marrow biopsies showed megakaryocyte hyperproliferation and dysplasia. Megakaryocytes obtained by culture of CD34 + stem cells confirmed hyperproliferation and showed reduced proplatelet formation. The effect of KDSR insufficiency on the sphingolipid profile was unknown, and was explored in vivo and in vitro by a broad metabolomics screen that indicated activation of an in vivo compensatory pathway that leads to normalization of downstream metabolites such as ceramide. Differentiation of propositus-derived induced pluripotent stem cells to megakaryocytes followed by expression of functional KDSR showed correction of the aberrant cellular and biochemical phenotypes, corroborating the critical role of KDSR in proplatelet formation. Finally, Kdsr depletion in zebrafish recapitulated the thrombocytopenia and showed biochemical changes similar to those observed in the affected siblings. These studies support an important role for sphingolipids as regulators of cytoskeletal organization during megakaryopoiesis and proplatelet formation., (Copyright© 2019 Ferrata Storti Foundation.)

Published
2019
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88. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity.

Author

Hendricks AE, Bochukova EG, Marenne G, Keogh JM, Atanassova N, Bounds R, Wheeler E, Mistry V, Henning E, Körner A, Muddyman D, McCarthy S, Hinney A, Hebebrand J, Scott RA, Langenberg C, Wareham NJ, Surendran P, Howson JM, Butterworth AS, Danesh J, Nordestgaard BG, Nielsen SF, Afzal S, Papadia S, Ashford S, Garg S, Millhauser GL, Palomino RI, Kwasniewska A, Tachmazidou I, O'Rahilly S, Zeggini E, Barroso I, and Farooqi IS

Subjects
Animals, Case-Control Studies, Chromogranins chemistry, Chromogranins genetics, Chromogranins metabolism, Female, GTP-Binding Protein alpha Subunits, Gs chemistry, GTP-Binding Protein alpha Subunits, Gs genetics, GTP-Binding Protein alpha Subunits, Gs metabolism, Humans, Male, Mice, Models, Molecular, Mutation, Obesity, Morbid diagnosis, Odds Ratio, Pediatric Obesity diagnosis, Pedigree, Protein Conformation, Rodentia, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Obesity, Morbid genetics, Pediatric Obesity genetics
Abstract

Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF~0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10 -3 ), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies.

Published
2017
Full Text
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