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475 results on '"Van Es, Michael A."'

3. Outcomes after robotic thymectomy in nonthymomatous versus thymomatous patients with acetylcholine-receptor-antibody-associated myasthenia gravis

Author

Marcuse, Florit, Hoeijmakers, Janneke G.J., Hochstenbag, Monique, Hamid, Myrurgia Abdul, Keijzers, Marlies, Mané-Damas, Marina, Martinez-Martinez, Pilar, Verschuuren, Jan, Kuks, Jan, Beekman, Roy, van der Kooi, Anneke J., van Doorn, Pieter, van Es, Michael, Maessen, Jos J.G., and De Baets, Marc H.V.

Published
2023
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4. Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosis

Author

Tazelaar, Gijs H.P., Hop, Paul J., Seelen, Meinie, van Vugt, Joke J.F.A., van Rheenen, Wouter, Kool, Lindy, van Eijk, Kristel R., Gijzen, Marleen, Dooijes, Dennis, Moisse, Matthieu, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Nordin, Angelica, Pardina, Jesus S. Mora, Ravits, John, Al-Chalabi, Ammar, Chio, Adriano, McLaughlin, Russell L., Hardiman, Orla, Van Damme, Philip, de Carvalho, Mamede, Neuwirth, Christoph, Weber, Markus, Andersen, Peter M, van den Berg, Leonard H., Veldink, Jan H., and van Es, Michael A.

Published
2023
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6. Structural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis

Author

Al Khleifat, Ahmad, Iacoangeli, Alfredo, van Vugt, Joke J. F. A., Bowles, Harry, Moisse, Matthieu, Zwamborn, Ramona A. J., van der Spek, Rick A. A., Shatunov, Aleksey, Cooper-Knock, Johnathan, Topp, Simon, Byrne, Ross, Gellera, Cinzia, López, Victoria, Jones, Ashley R., Opie-Martin, Sarah, Vural, Atay, Campos, Yolanda, van Rheenen, Wouter, Kenna, Brendan, Van Eijk, Kristel R., Kenna, Kevin, Weber, Markus, Smith, Bradley, Fogh, Isabella, Silani, Vincenzo, Morrison, Karen E., Dobson, Richard, van Es, Michael A., McLaughlin, Russell L., Vourc’h, Patrick, Chio, Adriano, Corcia, Philippe, de Carvalho, Mamede, Gotkine, Marc, Panades, Monica P., Mora, Jesus S., Shaw, Pamela J., Landers, John E., Glass, Jonathan D., Shaw, Christopher E., Basak, Nazli, Hardiman, Orla, Robberecht, Wim, Van Damme, Philip, van den Berg, Leonard H., Veldink, Jan H., and Al-Chalabi, Ammar

Published
2022
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7. Lithium carbonate in amyotrophic lateral sclerosis patients homozygous for the C-allele at SNP rs12608932 in UNC13A: protocol for a confirmatory, randomized, group-sequential, event-driven, double-blind, placebo-controlled trial

Author

Willemse, Sean W., Roes, Kit C. B., Van Damme, Philip, Hardiman, Orla, Ingre, Caroline, Povedano, Monica, Wray, Naomi R., Gijzen, Marleen, de Pagter, Mirjam S., Demaegd, Koen C., Janse, Annemarie F. C., Vink, Roel G., Sleutjes, Boudewijn T. H. M., Chiò, Adriano, Corcia, Philippe, Reviers, Evy, Al-Chalabi, Ammar, Kiernan, Matthew C., van den Berg, Leonard H., van Es, Michael A., and van Eijk, Ruben P. A.

Published
2022
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8. Senataxin mutations elicit motor neuron degeneration phenotypes and yield TDP-43 mislocalization in ALS4 mice and human patients

Author

Bennett, Craig L, Dastidar, Somasish G, Ling, Shuo-Chien, Malik, Bilal, Ashe, Travis, Wadhwa, Mandheer, Miller, Derek B, Lee, Changwoo, Mitchell, Matthew B, van Es, Michael A, Grunseich, Christopher, Chen, Yingzhang, Sopher, Bryce L, Greensmith, Linda, Cleveland, Don W, and La Spada, Albert R

Subjects
Biomedical and Clinical Sciences, Neurosciences, Neurodegenerative, ALS, Brain Disorders, Genetics, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Neurological, Amyotrophic Lateral Sclerosis, Animals, DNA Helicases, DNA-Binding Proteins, Female, Humans, Male, Mice, Motor Neurons, Multifunctional Enzymes, Nerve Degeneration, Phenotype, RNA Helicases, Amyotrophic lateral sclerosis, Senataxin, Transgenesis, Gene targeting, TDP-43, Nucleocytoplasmic transport, Ran, RanGAP1, Motor neuron, Neurodegeneration, Clinical Sciences, Neurology & Neurosurgery
Abstract

Amyotrophic lateral sclerosis type 4 (ALS4) is a rare, early-onset, autosomal dominant form of ALS, characterized by slow disease progression and sparing of respiratory musculature. Dominant, gain-of-function mutations in the senataxin gene (SETX) cause ALS4, but the mechanistic basis for motor neuron toxicity is unknown. SETX is a RNA-binding protein with a highly conserved helicase domain, but does not possess a low-complexity domain, making it unique among ALS-linked disease proteins. We derived ALS4 mouse models by expressing two different senataxin gene mutations (R2136H and L389S) via transgenesis and knock-in gene targeting. Both approaches yielded SETX mutant mice that develop neuromuscular phenotypes and motor neuron degeneration. Neuropathological characterization of SETX mice revealed nuclear clearing of TDP-43, accompanied by TDP-43 cytosolic mislocalization, consistent with the hallmark pathology observed in human ALS patients. Postmortem material from ALS4 patients exhibited TDP-43 mislocalization in spinal cord motor neurons, and motor neurons from SETX ALS4 mice displayed enhanced stress granule formation. Immunostaining analysis for nucleocytoplasmic transport proteins Ran and RanGAP1 uncovered nuclear membrane abnormalities in the motor neurons of SETX ALS4 mice, and nuclear import was delayed in SETX ALS4 cortical neurons, indicative of impaired nucleocytoplasmic trafficking. SETX ALS4 mice thus recapitulated ALS disease phenotypes in association with TDP-43 mislocalization and provided insight into the basis for TDP-43 histopathology, linking SETX dysfunction to common pathways of ALS motor neuron degeneration.

Published
2018

9. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author

van Rheenen, Wouter, van der Spek, Rick A. A., Bakker, Mark K., van Vugt, Joke J. F. A., Hop, Paul J., Zwamborn, Ramona A. J., de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Hannon, Eilis, Moisse, Matthieu, Baird, Denis, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M., Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs H. P., van Eijk, Kristel R., Kooyman, Maarten, Byrne, Ross P., Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N., Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E., Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thomas, Başak, Nazli, van der Kooi, Anneke J., Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D’Alfonso, Sandra, Sorarù, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chiò, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H., Bell, Shaughn, Vourc’h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stéphanie, Meininger, Vincent, Salachas, François, Mora Pardina, Jesus S., Assialioui, Abdelilah, Rojas-García, Ricardo, Dion, Patrick A., Ross, Jay P., Ludolph, Albert C., Weishaupt, Jochen H., Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Durr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nicholas W., Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, Kraft, Julia, Whiteman, David C., Olsen, Catherine M., Uitterlinden, Andre G., Hofman, Albert, Rietschel, Marcella, Cichon, Sven, Nöthen, Markus M., Amouyel, Philippe, Traynor, Bryan J., Singleton, Andrew B., Mitne Neto, Miguel, Cauchi, Ruben J., Ophoff, Roel A., Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, van Deerlin, Vivianna M., Grosskreutz, Julian, Roediger, Annekathrin, Gaur, Nayana, Jörk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Benjamin, Stubendorff, Beatrice, Witte, Otto W., Steinbach, Robert, Hübner, Christian A., Graff, Caroline, Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaž, Zidar, Janez, Ravnik-Glavač, Metka, Glavač, Damjan, Stević, Zorica, Drory, Vivian, Povedano, Monica, Blair, Ian P., Kiernan, Matthew C., Benyamin, Beben, Henderson, Robert D., Furlong, Sarah, Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Ngo, Shyuan T., Nicholson, Garth A., Pamphlett, Roger, Rowe, Dominic B., Steyn, Frederik J., Williams, Kelly L., Mather, Karen A., Sachdev, Perminder S., Henders, Anjali K., Wallace, Leanne, de Carvalho, Mamede, Pinto, Susana, Petri, Susanne, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Curtis, Charles J., Breen, Gerome, Glass, Jonathan D., Brown, Jr., Robert H., Landers, John E., Shaw, Christopher E., Andersen, Peter M., Groen, Ewout J. N., van Es, Michael A., Pasterkamp, R. Jeroen, Fan, Dongsheng, Garton, Fleur C., McRae, Allan F., Davey Smith, George, Gaunt, Tom R., Eberle, Michael A., Mill, Jonathan, McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Wray, Naomi R., Tsai, Ellen, Runz, Heiko, Franke, Lude, Al-Chalabi, Ammar, Van Damme, Philip, van den Berg, Leonard H., and Veldink, Jan H.

Published
2021
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14. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

Author

Logullo, Francesco O., Simone, Isabella, Logroscino, Giancarlo, Salvi, Fabrizio, Bartolomei, Ilaria, Borghero, Giuseppe, Murru, Maria Rita, Costantino, Emanuela, Pani, Carla, Puddu, Roberta, Caredda, Carla, Piras, Valeria, Tranquilli, Stefania, Cuccu, Stefania, Corongiu, Daniela, Melis, Maurizio, Milia, Antonio, Marrosu, Francesco, Marrosu, Maria Giovanna, Floris, Gianluca, Cannas, Antonino, Capasso, Margherita, Caponnetto, Claudia, Mancardi, Gianluigi, Origone, Paola, Mandich, Paola, Conforti, Francesca L., Cavallaro, Sebastiano, Mora, Gabriele, Marinou, Kalliopi, Sideri, Riccardo, Penco, Silvana, Mosca, Lorena, Lunetta, Christian, Pinter, Giuseppe Lauria, Corbo, Massimo, Riva, Nilo, Carrera, Paola, Volanti, Paolo, Mandrioli, Jessica, Fini, Nicola, Fasano, Antonio, Tremolizzo, Lucio, Arosio, Alessandro, Ferrarese, Carlo, Trojsi, Francesca, Tedeschi, Gioacchino, Monsurrò, Maria Rosaria, Piccirillo, Giovanni, Femiano, Cinzia, Ticca, Anna, Ortu, Enzo, La Bella, Vincenzo, Spataro, Rossella, Colletti, Tiziana, Sabatelli, Mario, Zollino, Marcella, Conte, Amelia, Luigetti, Marco, Lattante, Serena, Marangi, Giuseppe, Santarelli, Marialuisa, Petrucci, Antonio, Pugliatti, Maura, Pirisi, Angelo, Parish, Leslie D., Occhineri, Patrizia, Giannini, Fabio, Battistini, Stefania, Ricci, Claudia, Benigni, Michele, Cau, Tea B., Loi, Daniela, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Barberis, Marco, Restagno, Gabriella, Casale, Federico, Marrali, Giuseppe, Fuda, Giuseppe, Ossola, Irene, Cammarosano, Stefania, Canosa, Antonio, Ilardi, Antonio, Manera, Umberto, Grassano, Maurizio, Tanel, Raffaella, Pisano, Fabrizio, Harms, Matthew B., Goldstein, David B., Shneider, Neil A., Goutman, Stephen, Simmons, Zachary, Miller, Timothy M., Chandran, Siddharthan, Pal, Suvankar, Manousakis, Georgios, Appel, Stanley H., Simpson, Ericka, Wang, Leo, Baloh, Robert H., Gibson, Summer, Bedlack, Richard, Lacomis, David, Sareen, Dhruv, Sherman, Alexander, Bruijn, Lucie, Penny, Michelle, Allen, Andrew S., Appel, Stanley, Bedlack, Richard S., Boone, Braden E., Brown, Robert, Carulli, John P., Chesi, Alessandra, Chung, Wendy K., Cirulli, Elizabeth T., Cooper, Gregory M., Couthouis, Julien, Day-Williams, Aaron G., Dion, Patrick A., Gitler, Aaron D., Glass, Jonathan D., Han, Yujun, Harris, Tim, Hayes, Sebastian D., Jones, Angela L., Keebler, Jonathan, Krueger, Brian J., Lasseigne, Brittany N., Levy, Shawn E., Lu, Yi-Fan, Maniatis, Tom, McKenna-Yasek, Diane, Myers, Richard M., Petrovski, Slavé, Pulst, Stefan M., Raphael, Alya R., Ravits, John M., Ren, Zhong, Rouleau, Guy A., Sapp, Peter C., Sims, Katherine B., Staropoli, John F., Waite, Lindsay L., Wang, Quanli, Wimbish, Jack R., Xin, Winnie W., Phatnani, Hemali, Kwan, Justin, Broach, James R., Arcila-Londono, Ximena, Lee, Edward B., Van Deerlin, Vivianna M., Fraenkel, Ernest, Ostrow, Lyle W., Baas, Frank, Zaitlen, Noah, Berry, James D., Malaspina, Andrea, Fratta, Pietro, Cox, Gregory A., Thompson, Leslie M., Finkbeiner, Steve, Dardiotis, Efthimios, Hornstein, Eran, MacGowan, Daniel J., Heiman-Patterson, Terry, Hammell, Molly G., Patsopoulos, Nikolaos A., Dubnau, Joshua, Nath, Avindra, Kaye, Julia, Finkbeiner, Steven, Wyman, Stacia, LeNail, Alexander, Lima, Leandro, Rothstein, Jeffrey D., Svendsen, Clive N., Van Eyk, Jenny, Maragakis, Nicholas J., Kolb, Stephen J., Cudkowicz, Merit, Baxi, Emily, Benatar, Michael, Taylor, J. Paul, Wu, Gang, Rampersaud, Evadnie, Wuu, Joanne, Rademakers, Rosa, Züchner, Stephan, Schule, Rebecca, McCauley, Jacob, Hussain, Sumaira, Cooley, Anne, Wallace, Marielle, Clayman, Christine, Barohn, Richard, Statland, Jeffrey, Ravits, John, Swenson, Andrea, Jackson, Carlayne, Trivedi, Jaya, Khan, Shaida, Katz, Jonathan, Jenkins, Liberty, Burns, Ted, Gwathmey, Kelly, Caress, James, McMillan, Corey, Elman, Lauren, Pioro, Erik, Heckmann, Jeannine, So, Yuen, Walk, David, Maiser, Samuel, Zhang, Jinghui, Silani, Vincenzo, Ticozzi, Nicola, Gellera, Cinzia, Ratti, Antonia, Taroni, Franco, Lauria, Giuseppe, Verde, Federico, Fogh, Isabella, Tiloca, Cinzia, Comi, Giacomo P., Sorarù, Gianni, Cereda, Cristina, D’Alfonso, Sandra, Corrado, Lucia, De Marchi, Fabiola, Corti, Stefania, Ceroni, Mauro, Mazzini, Letizia, Siciliano, Gabriele, Filosto, Massimiliano, Inghilleri, Maurizio, Peverelli, Silvia, Colombrita, Claudia, Poletti, Barbara, Maderna, Luca, Del Bo, Roberto, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, Pensato, Viviana, Castellotti, Barbara, Camu, William, Mouzat, Kevin, Lumbroso, Serge, Corcia, Philippe, Meininger, Vincent, Besson, Gérard, Lagrange, Emmeline, Clavelou, Pierre, Guy, Nathalie, Couratier, Philippe, Vourch, Patrick, Danel, Véronique, Bernard, Emilien, Lemasson, Gwendal, Al Kheifat, Ahmad, Al-Chalabi, Ammar, Andersen, Peter, Basak, A. Nazli, Blair, Ian P., Chio, Adriano, Cooper-Knock, Jonathan, de Carvalho, Mamede, Dekker, Annelot, Drory, Vivian, Redondo, Alberto Garcia, Gotkine, Marc, Hardiman, Orla, Hide, Winston, Iacoangeli, Alfredo, Glass, Jonathan, Kenna, Kevin, Kiernan, Matthew, Kooyman, Maarten, Landers, John, McLaughlin, Russell, Middelkoop, Bas, Mill, Jonathan, Neto, Miguel Mitne, Moisse, Mattieu, Pardina, Jesus Mora, Morrison, Karen, Newhouse, Stephen, Pinto, Susana, Pulit, Sara, Robberecht, Wim, Shatunov, Aleksey, Shaw, Pamela, Shaw, Chris, Sproviero, William, Tazelaar, Gijs, van Damme, Philip, van den Berg, Leonard, van der Spek, Rick, van Eijk, Kristel, van Es, Michael, van Rheenen, Wouter, van Vugt, Joke, Veldink, Jan, Weber, Markus, Williams, Kelly L., Zatz, Mayana, Bauer, Denis C., Twine, Natalie A., Nicolas, Aude, Kenna, Kevin P., Renton, Alan E., Faghri, Faraz, Chia, Ruth, Dominov, Janice A., Kenna, Brendan J., Nalls, Mike A., Keagle, Pamela, Rivera, Alberto M., Murphy, Natalie A., van Vugt, Joke J.F.A., Geiger, Joshua T., Van der Spek, Rick A., Pliner, Hannah A., Shankaracharya, Smith, Bradley N., Topp, Simon D., Abramzon, Yevgeniya, Gkazi, Athina Soragia, Eicher, John D., Kenna, Aoife, Messina, Sonia, Simone, Isabella L., Ferrucci, Luigi, Moreno, Cristiane de Araujo Martins, Kamalakaran, Sitharthan, Musunuri, Rajeeva Lochan, Evani, Uday Shankar, Abhyankar, Avinash, Zody, Michael C., Wyman, Stacia K., LeNail, Alex, Van Eyk, Jennifer E., Laaksovirta, Hannu, Myllykangas, Liisa, Jansson, Lilja, Valori, Miko, Ealing, John, Hamdalla, Hisham, Rollinson, Sara, Pickering-Brown, Stuart, Orrell, Richard W., Sidle, Katie C., Hardy, John, Singleton, Andrew B., Johnson, Janel O., Arepalli, Sampath, Polak, Meraida, Asress, Seneshaw, Al-Sarraj, Safa, King, Andrew, Troakes, Claire, Vance, Caroline, de Belleroche, Jacqueline, ten Asbroek, Anneloor L.M.A., Muñoz-Blanco, José Luis, Hernandez, Dena G., Ding, Jinhui, Gibbs, J. Raphael, Scholz, Sonja W., Floeter, Mary Kay, Campbell, Roy H., Landi, Francesco, Bowser, Robert, MacGowan, Daniel J.L., Kirby, Janine, Pioro, Erik P., Pamphlett, Roger, Broach, James, Gerhard, Glenn, Dunckley, Travis L., Brady, Christopher B., Kowall, Neil W., Troncoso, Juan C., Le Ber, Isabelle, Heiman-Patterson, Terry D., Kamel, Freya, Van Den Bosch, Ludo, Strom, Tim M., Meitinger, Thomas, Van Eijk, Kristel R., Moisse, Matthieu, McLaughlin, Russell L., Van Es, Michael A., Boylan, Kevin B., Van Blitterswijk, Marka, Morrison, Karen E., Mora, Jesús S., Drory, Vivian E., Shaw, Pamela J., Turner, Martin R., Talbot, Kevin, Fifita, Jennifer A., Nicholson, Garth A., Esteban-Pérez, Jesús, García-Redondo, Alberto, Rogaeva, Ekaterina, Zinman, Lorne, Cooper-Knock, Johnathan, Brice, Alexis, Goutman, Stephen A., Feldman, Eva L., Gibson, Summer B., Van Damme, Philip, Ludolph, Albert C., Andersen, Peter M., Weishaupt, Jochen H., Trojanowski, John Q., Brown, Robert H., Jr., van den Berg, Leonard H., Veldink, Jan H., Stone, David J., Tienari, Pentti, Chiò, Adriano, Shaw, Christopher E., Traynor, Bryan J., and Landers, John E.

Published
2018
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17. KIF1A variants are a frequent cause of autosomal dominant hereditary spastic paraplegia

Author

Pennings, Maartje, Schouten, Meyke I., van Gaalen, Judith, Meijer, Rowdy P. P., de Bot, Susanne T., Kriek, Marjolein, Saris, Christiaan G. J., van den Berg, Leonard H., van Es, Michael A., Zuidgeest, Dick M. H., Elting, Mariet W., van de Kamp, Jiddeke M., van Spaendonck-Zwarts, Karin Y., Die-Smulders, Christine de, Brilstra, Eva H., Verschuuren, Corien C., de Vries, Bert B. A., Bruijn, Jacques, Sofou, Kalliopi, Duijkers, Floor A., Jaeger, B., Schieving, Jolanda H., van de Warrenburg, Bart P., and Kamsteeg, Erik-Jan

Published
2020
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19. Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author

van Rheenen, Wouter, van der Spek, Rick A. A., Bakker, Mark K., van Vugt, Joke J. F. A., Hop, Paul J., Zwamborn, Ramona A. J., de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Hannon, Eilis, Moisse, Matthieu, Baird, Denis, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M., Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs H. P., van Eijk, Kristel R., Kooyman, Maarten, Byrne, Ross P., Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N., Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E., Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thomas, Başak, Nazli, van der Kooi, Anneke J., Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D’Alfonso, Sandra, Sorarù, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chiò, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H., Bell, Shaughn, Vourc’h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stéphanie, Meininger, Vincent, Salachas, François, Mora Pardina, Jesus S., Assialioui, Abdelilah, Rojas-García, Ricardo, Dion, Patrick A., Ross, Jay P., Ludolph, Albert C., Weishaupt, Jochen H., Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Durr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nicholas W., Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, Kraft, Julia, Whiteman, David C., Olsen, Catherine M., Uitterlinden, Andre G., Hofman, Albert, Rietschel, Marcella, Cichon, Sven, Nöthen, Markus M., Amouyel, Philippe, Traynor, Bryan J., Singleton, Andrew B., Mitne Neto, Miguel, Cauchi, Ruben J., Ophoff, Roel A., Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, van Deerlin, Vivianna M., Grosskreutz, Julian, Roediger, Annekathrin, Gaur, Nayana, Jörk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Benjamin, Stubendorff, Beatrice, Witte, Otto W., Steinbach, Robert, Hübner, Christian A., Graff, Caroline, Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaž, Zidar, Janez, Ravnik-Glavač, Metka, Glavač, Damjan, Stević, Zorica, Drory, Vivian, Povedano, Monica, Blair, Ian P., Kiernan, Matthew C., Benyamin, Beben, Henderson, Robert D., Furlong, Sarah, Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Ngo, Shyuan T., Nicholson, Garth A., Pamphlett, Roger, Rowe, Dominic B., Steyn, Frederik J., Williams, Kelly L., Mather, Karen A., Sachdev, Perminder S., Henders, Anjali K., Wallace, Leanne, de Carvalho, Mamede, Pinto, Susana, Petri, Susanne, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Curtis, Charles J., Breen, Gerome, Glass, Jonathan D., Brown, Jr., Robert H., Landers, John E., Shaw, Christopher E., Andersen, Peter M., Groen, Ewout J. N., van Es, Michael A., Pasterkamp, R. Jeroen, Fan, Dongsheng, Garton, Fleur C., McRae, Allan F., Davey Smith, George, Gaunt, Tom R., Eberle, Michael A., Mill, Jonathan, McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Wray, Naomi R., Tsai, Ellen, Runz, Heiko, Franke, Lude, Al-Chalabi, Ammar, Van Damme, Philip, van den Berg, Leonard H., and Veldink, Jan H.

Published
2022
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20. No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis

Author

Goris, An, van Setten, Jessica, Diekstra, Frank, Ripke, Stephan, Patsopoulos, Nikolaos A, Sawcer, Stephen J, van Es, Michael, Andersen, Peter M, Melki, Judith, Meininger, Vincent, Hardiman, Orla, Landers, John E, Brown, Robert H, Shatunov, Aleksey, Leigh, Nigel, Al-Chalabi, Ammar, Shaw, Christopher E, Traynor, Bryan J, Chiò, Adriano, Restagno, Gabriella, Mora, Gabriele, Ophoff, Roel A, Oksenberg, Jorge R, Van Damme, Philip, Compston, Alastair, Robberecht, Wim, Dubois, Bénédicte, van den Berg, Leonard H, De Jager, Philip L, Veldink, Jan H, and de Bakker, Paul IW

Subjects
Human Genome, ALS, Multiple Sclerosis, Rare Diseases, Autoimmune Disease, Neurosciences, Genetics, Neurodegenerative, Clinical Research, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, Amyotrophic Lateral Sclerosis, Comorbidity, Genetic Predisposition to Disease, Humans, Polymorphism, Single Nucleotide, International Multiple Sclerosis Genetics Consortium, Australia and New Zealand MS Genetics Consortium, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Genome-wide association studies have been successful in identifying common variants that influence the susceptibility to complex diseases. From these studies, it has emerged that there is substantial overlap in susceptibility loci between diseases. In line with those findings, we hypothesized that shared genetic pathways may exist between multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). While both diseases may have inflammatory and neurodegenerative features, epidemiological studies have indicated an increased co-occurrence within individuals and families. To this purpose, we combined genome-wide data from 4088 MS patients, 3762 ALS patients and 12 030 healthy control individuals in whom 5 440 446 single-nucleotide polymorphisms (SNPs) were successfully genotyped or imputed. We tested these SNPs for the excess association shared between MS and ALS and also explored whether polygenic models of SNPs below genome-wide significance could explain some of the observed trait variance between diseases. Genome-wide association meta-analysis of SNPs as well as polygenic analyses fails to provide evidence in favor of an overlap in genetic susceptibility between MS and ALS. Hence, our findings do not support a shared genetic background of common risk variants in MS and ALS.

Published
2014

21. Assessment of risk of ALS conferred by the GGGGCC hexanucleotide repeat expansion in C9orf72 among first-degree relatives of patients with ALS carrying the repeat expansion.

Author

Van Wijk, Iris F., Van Eijk, Ruben P.A., Van Boxmeer, Loes, Westeneng, Henk-Jan, Van Es, Michael A., Van Rheenen, Wouter, Van Den Berg, Leonard H., Eijkemans, Marinus J.C., and Veldink, Jan H.

Subjects
RISK assessment, RANDOM effects model, RELATIVES
Abstract

We aimed to estimate the age-related risk of ALS in first-degree relatives of patients with ALS carrying the C9orf72 repeat expansion. We included all patients with ALS carrying a C9orf72 repeat expansion in The Netherlands. Using structured questionnaires, we determined the number of first-degree relatives, their age at death due to ALS or another cause, or age at time of questionnaire. The cumulative incidence of ALS among first-degree relatives was estimated, while accounting for death from other causes. Variability in ALS risk between families was evaluated using a random effects hazards model. We used a second, distinct approach to estimate the risk of ALS and FTD in the general population, using previously published data. In total, 214 of the 2,486 (9.2%) patients with ALS carried the C9orf72 repeat expansion. The mean risk of ALS at age 80 for first-degree relatives carrying the repeat expansion was 24.1%, but ranged between individual families from 16.0 to 60.6%. Using the second approach, we found the risk of ALS and FTD combined was 28.7% (95% CI 17.8%–54.3%) for carriers in the general population. On average, our estimated risk of ALS in the C9orf72 repeat expansion was lower compared to historical estimates. We showed, however, that the risk of ALS likely varies between families and one overall penetrance estimate may not be sufficient to describe ALS risk. This warrants a tailor-made, patient-specific approach in testing. Further studies are needed to assess the risk of FTD in the C9orf72 repeat expansion. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Familial motor neuron disease: co-occurrence of PLS and ALS (-FTD).

Author

de Boer, Eva M. J., Demaegd, Koen C., de Bie, Charlotte I., Veldink, Jan H., van den Berg, Leonard H., and van Es, Michael A.

Subjects
MOTOR neuron diseases, SPINAL muscular atrophy, AMYOTROPHIC lateral sclerosis, LITERATURE reviews, PATIENTS' families
Abstract

To report the frequency and characteristics of patients diagnosed with primary lateral sclerosis (PLS) with a positive family history for motor neuron diseases (MND) in the Netherlands and to compare our findings to the literature. Patients were identified through our ongoing, prospective population-based study on MND in The Netherlands, which also includes a standardized collection of patient characteristics, genetic testing, and family history. Only patients meeting the latest consensus criteria for definite PLS were included. The family history was considered positive for MND if any family members had been diagnosed with PLS, amyotrophic lateral sclerosis (ALS)(-FTD), or progressive muscular atrophy (PMA). Additionally, the literature was reviewed on PLS cases in which MND co-occurred within the same family. We identified 392 definite PLS cases, resulting in 9 families with a PLS patient and a positive family history for MND (2.3%). In only one of these pedigrees, a pathogenic variant (C9orf72 repeat expansion) was found. Our literature review revealed 23 families with a co-occurrence of PLS and MND, with 12 of them having a potentially pathogenic genetic variant. The consistent observation of PLS patients with a positive family history for MND, evident in both our study and the literature, implies the presence of shared underlying genetic factors between PLS and ALS. However, these factors are yet to be elucidated. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Development of a Rasch-Built Amyotrophic Lateral Sclerosis Impairment Multidomain Scale to Measure Disease Progression in ALS

Author

de Jongh, Adriaan D., primary, van Eijk, Ruben P.A., additional, Bakker, Leonhard A., additional, Bunte, Tommy M., additional, Beelen, Anita, additional, van der Meijden, Conny, additional, van Es, Michael A., additional, Visser-Meily, Johanna M.A., additional, Kruitwagen, Esther T., additional, Veldink, Jan H., additional, and van den Berg, Leonard H., additional

Published
2023
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24. Prognosis for patients with amyotrophic lateral sclerosis: development and validation of a personalised prediction model

Author

Westeneng, Henk-Jan, Debray, Thomas P A, Visser, Anne E, van Eijk, Ruben P A, Rooney, James P K, Calvo, Andrea, Martin, Sarah, McDermott, Christopher J, Thompson, Alexander G, Pinto, Susana, Kobeleva, Xenia, Rosenbohm, Angela, Stubendorff, Beatrice, Sommer, Helma, Middelkoop, Bas M, Dekker, Annelot M, van Vugt, Joke J F A, van Rheenen, Wouter, Vajda, Alice, Heverin, Mark, Kazoka, Mbombe, Hollinger, Hannah, Gromicho, Marta, Körner, Sonja, Ringer, Thomas M, Rödiger, Annekathrin, Gunkel, Anne, Shaw, Christopher E, Bredenoord, Annelien L, van Es, Michael A, Corcia, Philippe, Couratier, Philippe, Weber, Markus, Grosskreutz, Julian, Ludolph, Albert C, Petri, Susanne, de Carvalho, Mamede, Van Damme, Philip, Talbot, Kevin, Turner, Martin R, Shaw, Pamela J, Al-Chalabi, Ammar, Chiò, Adriano, Hardiman, Orla, Moons, Karel G M, Veldink, Jan H, and van den Berg, Leonard H

Published
2018
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27. Mapping of gene expression reveals CYP27A1 as a susceptibility gene for sporadic ALS.

Author

Diekstra, Frank P, Saris, Christiaan GJ, van Rheenen, Wouter, Franke, Lude, Jansen, Ritsert C, van Es, Michael A, van Vught, Paul WJ, Blauw, Hylke M, Groen, Ewout JN, Horvath, Steve, Estrada, Karol, Rivadeneira, Fernando, Hofman, Albert, Uitterlinden, Andre G, Robberecht, Wim, Andersen, Peter M, Melki, Judith, Meininger, Vincent, Hardiman, Orla, Landers, John E, Brown, Robert H, Shatunov, Aleksey, Shaw, Christopher E, Leigh, P Nigel, Al-Chalabi, Ammar, Ophoff, Roel A, van den Berg, Leonard H, and Veldink, Jan H

Subjects
Motor Neurons, Humans, Amyotrophic Lateral Sclerosis, Xanthomatosis, Cerebrotendinous, Genetic Predisposition to Disease, Gene Expression Profiling, Pedigree, Genotype, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genome-Wide Association Study, HapMap Project, Cholestanetriol 26-Monooxygenase, Xanthomatosis, Cerebrotendinous, Polymorphism, Single Nucleotide, General Science & Technology
Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disease characterized by loss of upper and lower motor neurons. ALS is considered to be a complex trait and genome-wide association studies (GWAS) have implicated a few susceptibility loci. However, many more causal loci remain to be discovered. Since it has been shown that genetic variants associated with complex traits are more likely to be eQTLs than frequency-matched variants from GWAS platforms, we conducted a two-stage genome-wide screening for eQTLs associated with ALS. In addition, we applied an eQTL analysis to finemap association loci. Expression profiles using peripheral blood of 323 sporadic ALS patients and 413 controls were mapped to genome-wide genotyping data. Subsequently, data from a two-stage GWAS (3,568 patients and 10,163 controls) were used to prioritize eQTLs identified in the first stage (162 ALS, 207 controls). These prioritized eQTLs were carried forward to the second sample with both gene-expression and genotyping data (161 ALS, 206 controls). Replicated eQTL SNPs were then tested for association in the second-stage GWAS data to find SNPs associated with disease, that survived correction for multiple testing. We thus identified twelve cis eQTLs with nominally significant associations in the second-stage GWAS data. Eight SNP-transcript pairs of highest significance (lowest p = 1.27 × 10(-51)) withstood multiple-testing correction in the second stage and modulated CYP27A1 gene expression. Additionally, we show that C9orf72 appears to be the only gene in the 9p21.2 locus that is regulated in cis, showing the potential of this approach in identifying causative genes in association loci in ALS. This study has identified candidate genes for sporadic ALS, most notably CYP27A1. Mutations in CYP27A1 are causal to cerebrotendinous xanthomatosis which can present as a clinical mimic of ALS with progressive upper motor neuron loss, making it a plausible susceptibility gene for ALS.

Published
2012

29. Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients

Author

Saris, Christiaan GJ, Horvath, Steve, van Vught, Paul WJ, van Es, Michael A, Blauw, Hylke M, Fuller, Tova F, Langfelder, Peter, DeYoung, Joseph, Wokke, John HJ, Veldink, Jan H, van den Berg, Leonard H, and Ophoff, Roel A

Abstract

Abstract Background Amyotrophic Lateral Sclerosis (ALS) is a lethal disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Diagnosis is mainly based on clinical symptoms, and there is currently no therapy to stop the disease or slow its progression. Since access to spinal cord tissue is not possible at disease onset, we investigated changes in gene expression profiles in whole blood of ALS patients. Results Our transcriptional study showed dramatic changes in blood of ALS patients; 2,300 probes (9.4%) showed significant differential expression in a discovery dataset consisting of 30 ALS patients and 30 healthy controls. Weighted gene co-expression network analysis (WGCNA) was used to find disease-related networks (modules) and disease related hub genes. Two large co-expression modules were found to be associated with ALS. Our findings were replicated in a second (30 patients and 30 controls) and third dataset (63 patients and 63 controls), thereby demonstrating a highly significant and consistent association of two large co-expression modules with ALS disease status. Ingenuity Pathway Analysis of the ALS related module genes implicates enrichment of functional categories related to genetic disorders, neurodegeneration of the nervous system and inflammatory disease. The ALS related modules contain a number of candidate genes possibly involved in pathogenesis of ALS. Conclusion This first large-scale blood gene expression study in ALS observed distinct patterns between cases and controls which may provide opportunities for biomarker development as well as new insights into the molecular mechanisms of the disease.

Published
2009

30. Gene-network analysis identifies susceptibility genes related to glycobiology in autism.

Author

van der Zwaag, Bert, Franke, Lude, Poot, Martin, Hochstenbach, Ron, Spierenburg, Henk A, Vorstman, Jacob AS, van Daalen, Emma, de Jonge, Maretha V, Verbeek, Nienke E, Brilstra, Eva H, van 't Slot, Ruben, Ophoff, Roel A, van Es, Michael A, Blauw, Hylke M, Veldink, Jan H, Buizer-Voskamp, Jacobine E, Beemer, Frits A, van den Berg, Leonard H, Wijmenga, Cisca, van Amstel, Hans Kristian Ploos, van Engeland, Herman, Burbach, J Peter H, and Staal, Wouter G

Subjects
Brain, Animals, Humans, Mice, Genetic Predisposition to Disease, Oligonucleotide Array Sequence Analysis, Case-Control Studies, Reproducibility of Results, Autistic Disorder, Chromosome Segregation, Gene Expression Regulation, Developmental, Gene Dosage, Haplotypes, Genome, Human, Software, Gene Regulatory Networks, Glycomics, Gene Expression Regulation, Developmental, Genome, Human, General Science & Technology
Abstract

The recent identification of copy-number variation in the human genome has opened up new avenues for the discovery of positional candidate genes underlying complex genetic disorders, especially in the field of psychiatric disease. One major challenge that remains is pinpointing the susceptibility genes in the multitude of disease-associated loci. This challenge may be tackled by reconstruction of functional gene-networks from the genes residing in these loci. We applied this approach to autism spectrum disorder (ASD), and identified the copy-number changes in the DNA of 105 ASD patients and 267 healthy individuals with Illumina Humanhap300 Beadchips. Subsequently, we used a human reconstructed gene-network, Prioritizer, to rank candidate genes in the segmental gains and losses in our autism cohort. This analysis highlighted several candidate genes already known to be mutated in cognitive and neuropsychiatric disorders, including RAI1, BRD1, and LARGE. In addition, the LARGE gene was part of a sub-network of seven genes functioning in glycobiology, present in seven copy-number changes specifically identified in autism patients with limited co-morbidity. Three of these seven copy-number changes were de novo in the patients. In autism patients with a complex phenotype and healthy controls no such sub-network was identified. An independent systematic analysis of 13 published autism susceptibility loci supports the involvement of genes related to glycobiology as we also identified the same or similar genes from those loci. Our findings suggest that the occurrence of genomic gains and losses of genes associated with glycobiology are important contributors to the development of ASD.

Published
2009

31. Genetic variability in sporadic amyotrophic lateral sclerosis

Author

Van Daele, Sien Hilde, primary, Moisse, Matthieu, additional, van Vugt, Joke J F A, additional, Zwamborn, Ramona A J, additional, van der Spek, Rick, additional, van Rheenen, Wouter, additional, Van Eijk, Kristel, additional, Kenna, Kevin, additional, Corcia, Philippe, additional, Vourc'h, Patrick, additional, Couratier, Philippe, additional, Hardiman, Orla, additional, McLaughin, Russell, additional, Gotkine, Marc, additional, Drory, Vivian, additional, Ticozzi, Nicola, additional, Silani, Vincenzo, additional, Ratti, Antonia, additional, de Carvalho, Mamede, additional, Mora Pardina, Jesús S, additional, Povedano, Monica, additional, Andersen, Peter M, additional, Weber, Markus, additional, Başak, Nazli A, additional, Shaw, Chris, additional, Shaw, Pamela J, additional, Morrison, Karen E, additional, Landers, John E, additional, Glass, Jonathan D, additional, van Es, Michael, additional, van den Berg, Leonard H, additional, Al-Chalabi, Ammar, additional, Veldink, Jan, additional, and Van Damme, Philip, additional

Published
2023
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33. Prospective natural history study of C9orf72 ALS clinical characteristics and biomarkers

Author

Cammack, Alexander J., Atassi, Nazem, Hyman, Theodore, van den Berg, Leonard H., Harms, Matthew, Baloh, Robert H., Brown, Robert H., van Es, Michael A., Veldink, Jan H., de Vries, Balint S., Rothstein, Jeffrey D., Drain, Caroline, Jockel-Balsarotti, Jennifer, Malcolm, Amber, Boodram, Sonia, Salter, Amber, Wightman, Nicholas, Yu, Hong, Sherman, Alexander V., Esparza, Thomas J., McKenna-Yasek, Diane, Owegi, Margaret A., Douthwright, Catherine, McCampbell, Alexander, Ferguson, Toby, Cruchaga, Carlos, Cudkowicz, Merit, and Miller, Timothy M.

Published
2019
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34. UNC13Ain amyotrophic lateral sclerosis: from genetic association to therapeutic target

Author

Willemse, Sean W, primary, Harley, Peter, additional, van Eijk, Ruben P A, additional, Demaegd, Koen C, additional, Zelina, Pavol, additional, Pasterkamp, R Jeroen, additional, van Damme, Philip, additional, Ingre, Caroline, additional, van Rheenen, Wouter, additional, Veldink, Jan H, additional, Kiernan, Matthew C, additional, Al-Chalabi, Ammar, additional, van den Berg, Leonard H, additional, Fratta, Pietro, additional, and van Es, Michael A, additional

Published
2023
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35. Longitudinal Effects of Asymptomatic C9orf72 Carriership on Brain Morphology

Author

van Veenhuijzen, Kevin, primary, Westeneng, Henk‐Jan, additional, Tan, Harold H. G., additional, Nitert, Abram D., additional, van der Burgh, Hannelore K., additional, Gosselt, Isabel, additional, van Es, Michael A., additional, Nijboer, Tanja C. W., additional, Veldink, Jan H., additional, and van den Berg, Leonard H., additional

Published
2022
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36. Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data

Author

Al Khleifat, Ahmad, primary, Iacoangeli, Alfredo, additional, Jones, Ashley R., additional, van Vugt, Joke J. F. A., additional, Moisse, Matthieu, additional, Shatunov, Aleksey, additional, Zwamborn, Ramona A. J., additional, van der Spek, Rick A. A., additional, Cooper-Knock, Johnathan, additional, Topp, Simon, additional, van Rheenen, Wouter, additional, Kenna, Brendan, additional, Van Eijk, Kristel R., additional, Kenna, Kevin, additional, Byrne, Ross, additional, López, Victoria, additional, Opie-Martin, Sarah, additional, Vural, Atay, additional, Campos, Yolanda, additional, Weber, Markus, additional, Smith, Bradley, additional, Fogh, Isabella, additional, Silani, Vincenzo, additional, Morrison, Karen E., additional, Dobson, Richard, additional, van Es, Michael A., additional, McLaughlin, Russell L., additional, Vourc’h, Patrick, additional, Chio, Adriano, additional, Corcia, Philippe, additional, de Carvalho, Mamede, additional, Gotkine, Marc, additional, Panades, Monica Povedano, additional, Mora, Jesus S., additional, Shaw, Pamela J., additional, Landers, John E., additional, Glass, Jonathan D., additional, Shaw, Christopher E., additional, Basak, Nazli, additional, Hardiman, Orla, additional, Robberecht, Wim, additional, Van Damme, Philip, additional, van den Berg, Leonard H., additional, Veldink, Jan H., additional, and Al-Chalabi, Ammar, additional

Published
2022
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38. UNC13A in amyotrophic lateral sclerosis: from genetic association to therapeutic target.

Author

Willemse, Sean W., Harley, Peter, van Eijk, Ruben P. A., Demaegd, Koen C., Zelina, Pavol, Pasterkamp, R. Jeroen, van Damme, Philip, Ingre, Caroline, van Rheenen, Wouter, Veldink, Jan H., Kiernan, Matthew C., Al-Chalabi, Ammar, van den Berg, Leonard H., Fratta, Pietro, and van Es, Michael A.

Subjects
AMYOTROPHIC lateral sclerosis, LOCUS (Genetics), DRUG target, MOTOR neuron diseases, GENETIC testing, FRONTOTEMPORAL lobar degeneration, SPASTICITY
Published
2023
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43. Association of NIPA1 repeat expansions with amyotrophic lateral sclerosis in a large international cohort

Author

Tazelaar, Gijs H.P., Dekker, Annelot M., van Vugt, Joke J.F.A., van der Spek, Rick A., Westeneng, Henk-Jan, Kool, Lindy J.B.G., Kenna, Kevin P., van Rheenen, Wouter, Pulit, Sara L., McLaughlin, Russell L., Sproviero, William, Iacoangeli, Alfredo, Hübers, Annemarie, Brenner, David, Morrison, Karen E., Shaw, Pamela J., Shaw, Christopher E., Panadés, Monica Povedano, Mora Pardina, Jesus S., Glass, Jonathan D., Hardiman, Orla, Al-Chalabi, Ammar, van Damme, Philip, Robberecht, Wim, Landers, John E., Ludolph, Albert C., Weishaupt, Jochen H., van den Berg, Leonard H., Veldink, Jan H., and van Es, Michael A.

Published
2019
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44. Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials

Author

van Eijk, Ruben P.A., Jones, Ashley R., Sproviero, William, Shatunov, Aleksey, Shaw, Pamela J., Leigh, P. Nigel, Young, Carolyn A., Shaw, Christopher E., Mora, Gabriele, Mandrioli, Jessica, Borghero, Giuseppe, Volanti, Paolo, Diekstra, Frank P., van Rheenen, Wouter, Verstraete, Esther, Eijkemans, Marinus J.C., Veldink, Jan H., Chio, Adriano, Al-Chalabi, Ammar, van den Berg, Leonard H., and van Es, Michael A.

Published
2017
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45. Longitudinal Effects of Asymptomatic C9orf72 Carriership on Brain Morphology.

Author

van Veenhuijzen, Kevin, Westeneng, Henk‐Jan, Tan, Harold H. G., Nitert, Abram D., van der Burgh, Hannelore K., Gosselt, Isabel, van Es, Michael A., Nijboer, Tanja C. W., Veldink, Jan H., and van den Berg, Leonard H.

Subjects
EFFERENT pathways, PARIETAL lobe, MOTOR cortex, MORPHOLOGY, AMYOTROPHIC lateral sclerosis
Abstract

Objective: We investigated effects of C9orf72 repeat expansion and gene expression on longitudinal cerebral changes before symptom onset. Methods: We enrolled 79 asymptomatic family members (AFMs) from 9 families with C9orf72 repeat expansion. Twenty‐eight AFMs carried the mutation (C9+). Participants had up to 3 magnetic resonance imaging (MRI) scans, after which we compared motor cortex and motor tracts between C9+ and C9− AFMs using mixed effects models, incorporating kinship to correct for familial relations and lessen effects of other genetic factors. We also compared cortical, subcortical, cerebellar, and connectome structural measurements in a hypothesis‐free analysis. We correlated regional C9orf72 expression in donor brains with the pattern of cortical thinning in C9+ AFMs using meta‐regression. For comparison, we included 42 C9+ and 439 C9− patients with amyotrophic lateral sclerosis (ALS) in this analysis. Results: C9+ AFM motor cortex had less gyrification and was thinner than in C9− AFMs, without differences in motor tracts. Whole brain analysis revealed thinner cortex and less gyrification in parietal, occipital, and temporal regions, smaller thalami and right hippocampus, and affected frontotemporal connections. Thinning of bilateral precentral, precuneus, and left superior parietal cortex was faster in C9+ than in C9− AFMs. Higher C9orf72 expression correlated with thinner cortex in both C9+ AFMs and C9+ ALS patients. Interpretation: In asymptomatic C9orf72 repeat expansion carriers, brain MRI reveals widespread features suggestive of impaired neurodevelopment, along with faster decline of motor and parietal cortex than found in normal aging. C9orf72 expression might play a role in cortical development, and consequently explain the specific brain abnormalities of mutation carriers. ANN NEUROL 2023;93:668–680 [ABSTRACT FROM AUTHOR]

Published
2023
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46. Evaluating the influence of alcohol intoxication on the pre-hospital identification of severe head injury: a multi-center, cohort study.

Author

Lokerman, Robin D., Gulickx, Max, Waalwijk, Job F., van Es, Michael A., Tuinema, Rinske M., Leenen, Luke P.H., and van Heijl, Mark

Subjects
RESEARCH, CONFIDENCE intervals, ALCOHOLIC intoxication, RETROSPECTIVE studies, PATIENTS, TRANSPORTATION of patients, SEVERITY of illness index, RISK assessment, EMERGENCY medical services, GLASGOW Coma Scale, DESCRIPTIVE statistics, RESEARCH funding, ODDS ratio, HEAD injuries, MEDICAL needs assessment, EMERGENCY medicine, LONGITUDINAL method, DISEASE risk factors
Abstract

To determine the influence of intoxication on the pre-hospital recognition of severely head-injured patients by Emergency Medical Services (EMS) professionals and to investigate the relationship between suspected alcohol intoxication and severe head injury. This multi-center, retrospective, cohort study included trauma patients, aged ≥ 16 years, transported by an ambulance of the Regional Ambulance Facility Utrecht to any emergency department in the participating trauma regions. Between January 1, 2015 and December 31, 2017, 19,206 patients were included, of whom 1167 (6.0%) were suspected to have a severe head injury in the field, and 623 (3.2%) were diagnosed with such an injury at the hospital. These injuries were less frequently recognized in patients with a GCS ≥ 13 than in patients with a GCS < 13 (25.0% vs. 76.2%). Patients suspected to be intoxicated had a higher chance to suffer from severe head injury (OR 1.42, 95%-CI 1.22–1.65) and were recognized slightly more often (45.3% vs. 40.2%). Severe head injuries are difficult to recognize in the field, especially in patients without a decreased GCS. Suspicion of alcohol intoxication did not seem to influence pre-hospital injury recognition, as it possibly makes a severe head injury harder to recognize and simultaneously raises caution for a severe injury. [ABSTRACT FROM AUTHOR]

Published
2023
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47. Facial Onset Sensory and Motor Neuronopathy

Author

de Boer, Eva M.J., Barritt, Andrew W., Elamin, Marwa, Anderson, Stuart J., Broad, Rebecca, Nisbet, Angus, Goedee, H. Stephan, Vázquez Costa, Juan F., Prudlo, Johannes, Vedeler, Christian A., Fernandez, Julio Pardo, Panades, Mónica Povedano, Albertí Aguilo, Maria A., Bella, Eleonora Dalla, Lauria, Giuseppe, Pinto, Wladimir B.V.R., de Souza, Paulo V.S., Oliveira, Acary S.B., Toro, Camilo, van Iersel, Joost, Parson, Malu, Harschnitz, Oliver, van den Berg, Leonard H., Veldink, Jan H., Al-Chalabi, Ammar, Leigh, Peter N., and van Es, Michael A.

Subjects
Malalties autoimmunitàries, Autoimmune diseases, Malalties neurodegeneratives, Neurodegenerative diseases, mental disorders, Review, Malalties rares, Rare diseases
Abstract

Purpose of review: To improve our clinical understanding of facial onset sensory and motor neuronopathy (FOSMN). Recent findings: We identified 29 new cases and 71 literature cases, resulting in a cohort of 100 patients with FOSMN. During follow-up, cognitive and behavioral changes became apparent in 8 patients, suggesting that changes within the spectrum of frontotemporal dementia (FTD) are a part of the natural history of FOSMN. Another new finding was chorea, seen in 6 cases. Despite reports of autoantibodies, there is no consistent evidence to suggest an autoimmune pathogenesis. Four of 6 autopsies had TAR DNA-binding protein (TDP) 43 pathology. Seven cases had genetic mutations associated with neurodegenerative diseases. Summary: FOSMN is a rare disease with a highly characteristic onset and pattern of disease progression involving initial sensory disturbances, followed by bulbar weakness with a cranial to caudal spread of pathology. Although not conclusive, the balance of evidence suggests that FOSMN is most likely to be a TDP-43 proteinopathy within the amyotrophic lateral sclerosis-FTD spectrum.

Published
2021

48. Distal spinal muscular atrophy featured by predominant calf muscle involvement in VRK1 associated disease – case series and review.

Author

Demaegd, Koen, primary, Brilstra, Eva H., additional, Hoogendijk, Jessica E., additional, de Bie, Charlotte I., additional, de Pagter, Mirjam S., additional, van Hecke, Wim, additional, Mühlebner, Angelika, additional, van Es, Michael A., additional, Milone, Margherita, additional, and van Rheenen, Wouter, additional

Published
2022
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49. Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS

Author

Hop, Paul J., Zwamborn, Ramona A. J., Hannon, Eilis, Shireby, Gemma L., Nabais, Marta F., Walker, Emma M., van Rheenen, Wouter, van Vugt, Joke J. F. A., Dekker, Annelot M., Westeneng, Henk-Jan, Tazelaar, Gijs H. P., Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, van Heemst, Diana, Veldink, Jan H., van den Berg, Leonard H., van Duijn, Cornelia M., Hofman, Bert A., Isaacs, Aaron, Uitterlinden, Andre G., van Eijk, Kristel R., van Meurs, Joyce, Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, Moisse, Matthieu, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha V., Jansen, Rick, van ‘t Hof, Peter, Deelen, Patrick, Nooren, Irene, t Hoen, Peter A. C., Heijmans, Bastiaan T., Moed, Matthijs, Baird, Denis, Franke, Lude, Vermaat, Martijn, Luijk, Rene, Jan Bonder, Marc, van Dijk, Freerk, Arindrarto, Wibowo, Al Khleifat, Ahmad, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik W., Al-Chalabi, Ammar, Wray, Naomi R., Bensimon, Gilbert, Hardiman, Orla, Iacoangeli, Alfredo, Chio, Adriano, Smith, George Davey, Mill, Jonathan, Ticozzi, Nicola, Ratti, Antonia, Cooper-Knock, Jonathan, Morrison, Karen E., Shaw, Pamela J., Basak, A. Nazli, Chiò, Adriano, Calvo, Andrea, Moglia, Cristina, Canosa, Antonio, Brunetti, Maura, Grassano, Maurizio, Gotkine, Marc, Lerner, Yossef, Zabari, Michal, Vourc’h, Patrick, Corcia, Philippe, Couratier, Philippe, Mora Pardina, Jesus S., Salas, Teresa, Dion, Patrick, Ross, Jay P., Henderson, Robert D., Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Nicholson, Garth, Rowe, Dominic B., Pamphlett, Roger, Mather, Karen A., Sachdev, Perminder S., Furlong, Sarah, Garton, Fleur C., Henders, Anjali K., Lin, Tian, Ngo, Shyuan T., Steyn, Frederik J., Wallace, Leanne, Williams, Kelly L., Neto, Miguel Mitne, Cauchi, Ruben J., Blair, Ian P., Kiernan, Matthew C., Drory, Vivian, Povedano, Monica, Carvalho, Mamede, Pinto, Susana, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Landers, John E., Shaw, Christopher E., Andersen, Peter M., McRae, Allan F., van Es, Michael A., Pasterkamp, R. Jeroen, McLaughlin, Russell L., Kenna, Kevin P., Tsai, Ellen, Runz, Heiko, Van Damme, Philip, Boomsma, Dorret I., Pool, Rene, van Dongen, Jenny, Hottenga, Joukje J., van Greevenbroek, Marleen M. J., Stehouwer, Coen D.A., van der Kallen, Carla J.H., Schalkwijk, Casper G., Wijmenga, Cisca, Zhernakova, Sasha, Tigchelaar, Ettje F., Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Laboratory Medicine, APH - Mental Health, Internal Medicine, Epidemiology, and Repositório da Universidade de Lisboa

Subjects
Cholesterol, Amyotrophic Lateral Sclerosis, Humans, Neurodegenerative Diseases, General Medicine, DNA Methylation, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], Article, Epigenesis, Genetic, Genome-Wide Association Study
Abstract

Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works., Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions., The research reported in this publication was supported by grants from The Dutch Research Council (NWO) (VENI scheme grant 09150161810018 to W.v.R.) and Prinses Beatrix Spierfond (neuromuscular fellowship grant W.F19-03 to W.v.R.), The Prinses Beatrix Spierfonds (W.OR20-08 to J.J.F.A.v.V. and J.H.V.), The Canadian Institutes of Health Research (FRN 159279 to J.P.R.), The Dutch Research Council (NWO) (VIDI grant 91719350 to K.P.K.), The European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 772376-EScORIAL to J.H.V.), the Swedish Brain Foundation (grant nos. 2012-0262, 2012-0305, 2013-0279, 2016-0303, 2018-0310, and 2020-0353 to P.M.A.), the Swedish Research Council (grant nos. 2012-3167 and 2017-03100 to P.M.A.), the Knut and Alice Wallenberg Foundation (grant nos. 2012.0091, 2014.0305, and 2020.0232 to P.M.A.), the Ulla-Carin Lindquist Foundation and the Västerbotten County Council (grant no. 56103-7002829 to P.M.A.), and King Gustaf V’s and Queen Victoria’s Freemason’s Foundation. This is an EU Joint Programme–Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organizations under the aegis of JPND (www.jpnd.eu) [United Kingdom, Medical Research Council (MR/L501529/1; MR/R024804/1) and Economic and Social Research Council (ES/L008238/1)] and through the Motor Neurone Disease Association (MNDA). This study represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. A.A.-C. is supported by an NIHR Senior Investigator Award. Samples used in this research were entirely/in part obtained from the U.K. National DNA Bank for MND Research, funded by the MND Association and the Wellcome Trust. We would like to thank people with MND and their families for their participation in this project. We acknowledge sample management undertaken by Biobanking Solutions funded by the Medical Research Council at the Centre for Integrated Genomic Medical Research, University of Manchester. R.J.P. is funded through the Gravitation program of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (BRAINSCAPES). G.L.S. was supported by a PhD studentship from the Alzheimer’s Society. S.T.N. acknowledges support through a FightMND Mid-Career Fellowship. V.S. is supported by the Italian Ministry of Health, AriSLA, and E-Rare Joint Transnational Call. A.A.K. is funded by the MNDA and NIHR Maudsley Biomedical Research Centre. D.B., E.T., and H.R. are employees of Biogen. L.H.v.d.B. reports grants from the Netherlands ALS Foundation, grants from The Netherlands Organization for Health Research and Development (Vici scheme), grants from The European Community’s Health Seventh Framework Programme [grant agreement no. 259867 (EuroMOTOR) to L.H.v.d.B.], and grants from The Netherlands Organization for Health Research and Development (the STRENGTH project, funded through the EU Joint Programme–Neurodegenerative Disease Research, JPND), during the conduct of the study. Project MinE Belgium was supported by a grant from IWT (no. 140935), the ALS Liga België, the National Lottery of Belgium, and the KU Leuven Opening the Future Fund. P.V.D. holds a senior clinical investigatorship of FWO-Vlaanderen and is supported by the E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders, the ALS Liga België, and the KU Leuven funds “Een Hart voor ALS”, “Laeversfonds voor ALS Onderzoek”, and the “Valéry Perrier Race against ALS Fund”. This work was supported by the Italian Ministry of Health (Ministero della Salute, Ricerca Sanitaria Finalizzata, grant RF-2016-02362405 to A. Chiò), the Progetti di Rilevante Interesse Nazionale program of the Ministry of Education, University and Research (grant 2017SNW5MB to A. Chiò); the European Commission’s Health Seventh Framework Programme (FP7/2007-2013 under grant agreement 259867 to A. Chiò), and the Joint Programme–Neurodegenerative Disease Research (Strength, ALS-Care and Brain-Mend projects), granted by Italian Ministry of Education, University, and Research. This study was performed under the Department of Excellence grant of the Italian Ministry of Education, University and Research to the “Rita Levi Montalcini” Department of Neuroscience, University of Torino, Italy. We acknowledge funding from the Australian National Health and Medical Research (NHMRC) Council: 1151854, 1083187, 1173790, 1078901, 1113400, 1095215, and 1176913 Enabling Grant #402703 to N.R.W. Additional funding was provided by the Motor Neurone Disease Research Institute of Australia Ice Bucket Challenge grant for the SALSA-SGC consortium. The OATS (used for controls) was facilitated through Twins Research Australia, a national resource in part supported by a Centre for Research Excellence from the Australian NHMRC Council (NHMRC 1079102 to N.R.W.). Funding for this study was awarded by the (NHMRC)/Australian Research Council Strategic Award (grant 401162 to N.R.W.) and NHMRC grants (1405325, 1024224, 1025243, 1045325, 1085606, 568969, and 1093083 to N.R.W.). The collaboration project is cofunded by the PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships. This study was supported by the ALS Foundation Netherlands. This work was sponsored by NWO Domain Science for the use of the national computer facilities. A.N.B. is grateful to the Suna and Inan Kirac Foundation and Koc University for the excellent research environment created and for financial support. G.A.R. is supported by the Canadian Institutes of Health. Several authors of this publication are members of the Netherlands Neuromuscular Center (NL-NMD) and the European Reference Network for rare neuromuscular diseases EURO-NMD. French ALS patients of the Pitié-Salpêtrière hospital (Paris) have been collected with ARSla funding support.

Published
2022

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