135 results on '"Van Es, Michael A."'
Search Results
2. Structural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis
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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
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- 2022
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3. 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
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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.
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- 2022
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4. Senataxin mutations elicit motor neuron degeneration phenotypes and yield TDP-43 mislocalization in ALS4 mice and human patients
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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
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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.
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- 2018
5. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
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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.
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- 2018
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6. Incidence, causes and consequences of moderate and severe traumatic brain injury as determined by Abbreviated Injury Score in the Netherlands
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Jochems, Denise, van Rein, Eveline, Niemeijer, Menco, van Heijl, Mark, van Es, Michael A., Nijboer, Tanja, Leenen, Luke P. H., Houwert, R. Marijn, and van Wessem, Karlijn J. P.
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- 2021
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7. KIF1A variants are a frequent cause of autosomal dominant hereditary spastic paraplegia
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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
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- 2020
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8. No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis
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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
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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.
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- 2014
9. Mapping of gene expression reveals CYP27A1 as a susceptibility gene for sporadic ALS.
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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
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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.
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- 2012
10. Discussing personalized prognosis in amyotrophic lateral sclerosis: development of a communication guide
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van Eenennaam, Remko M., Kruithof, Willeke J., van Es, Michael A., Kruitwagen-van Reenen, Esther T., Westeneng, Henk-Jan, Visser-Meily, Johanna M. A., van den Berg, Leonard H., and Beelen, Anita
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- 2020
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11. Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients
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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.
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- 2009
12. Gene-network analysis identifies susceptibility genes related to glycobiology in autism.
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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
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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.
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- 2009
13. Genetic variability in sporadic amyotrophic lateral sclerosis
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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
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- 2023
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14. Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data
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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
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- 2022
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15. Rhabdomyolysis after COVID-19 Comirnaty Vaccination: A Case Report
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Ruijters, Veerle J., primary, van der Meulen, Marjon F.G., additional, van Es, Michael A., additional, Smit, Tessa, additional, and Hoogendijk, Jessica E., additional
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- 2022
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16. Facial Onset Sensory and Motor Neuronopathy
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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.
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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.
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- 2021
17. Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
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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
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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.
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- 2022
18. Cortical and subcortical changes in resting-state neuronal activity and connectivity in early symptomatic ALS and advanced frontotemporal dementia
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Govaarts, Rosanne, primary, Beeldman, Emma, additional, Fraschini, Matteo, additional, Griffa, Alessandra, additional, Engels, Marjolein M.A., additional, van Es, Michael A., additional, Veldink, Jan H., additional, van den Berg, Leonard H., additional, van der Kooi, Anneke J., additional, Pijnenburg, Yolande A.L., additional, de Visser, Marianne, additional, Stam, Cornelis J., additional, Raaphorst, Joost, additional, and Hillebrand, Arjan, additional
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- 2022
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19. Epidemiology of paediatric moderate and severe traumatic brain injury in the Netherlands
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Jochems, Denise, van Rein, Eveline, Niemeijer, Menco, van Heijl, M., van Es, Michael A., Nijboer, Tanja, Leenen, L.P.H., Houwert, R.M., van Wessem, Karlijn J.P., Leerstoel Postma, Helmholtz Institute, and Experimental Psychology (onderzoeksprogramma PF)
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Traumatic brain injury ,Paediatric ,Epidemiology ,Incidence - Abstract
Introduction Traumatic brain injury (TBI) is the main cause of death in children around the world. The last Dutch epidemiological study described the incidence over 10 years ago. Mechanism of injury seems to change with the age of the child, therefore it is important to appreciate different age groups. To be able to lower the impact of childhood TBI, an understanding of current incidence, mechanism of injury and outcome is necessary. Methods A nationwide retrospective cohort study was conducted. The Dutch National Trauma Database was used to identify all patients 18 years and younger who were admitted to a Dutch hospital with moderate-severe TBI (Abbreviated Injury Score≥3) in the Netherlands, from January 2015 until December 2017. Subanalyses were done for different age groups. Results In total, 1413 patients were included, of whom 5% died. The incidence rate of moderate-severe TBI was 14/100,000 person years. Median age was 10.4 years. Largest age group was patients
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- 2021
20. Reduced Expression of the Kinesin-Associated Protein 3 (KIFAP3) Gene Increases Survival in Sporadic Amyotrophic Lateral Sclerosis
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Landers, John E., Melki, Judith, Meininger, Vincent, Glass, Jonathan D., van den Berg, Leonard H., van Es, Michael A., Sapp, Peter C., van Vught, Paul W. J., McKenna-Yasek, Diane M., Blauw, Hylke M., Cho, Ting-Jan, Polak, Meraida, Shi, Lijia, Wills, Anne-Marie, Broom, Wendy J., Ticozzi, Nicola, Silani, Vincenzo, Ozoguz, Aslihan, Rodriguez-Leyva, Ildefonso, Veldink, Jan H., Ivinson, Adrian J., Saris, Christiaan G. J., Hosier, Betsy A., Bames-Nessa, Alayna, Couture, Nicole, Wokke, John H. J., Kwiatkowski,, Thomas J., Ophoff, Roel A., Cronin, Simon, Hardiman, Orla, Diekstra, Frank P., Leigh, P. Nigel, Shaw, Christopher E., Simpson, Claire L., Hansen, Valerie K., Powell, John F., Corcia, Philippe, Salachas, François, Heath, Simon, Galan, Pilar, Georges, Franck, Horvitz, H. Robert, Lathrop, Mark, Purcell, Shaun, Al-Chalabi, Ammar, Brown,, Robert H., and Housman, David E.
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- 2009
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21. Discussing Personalized Prognosis Empowers Patients with Amyotrophic Lateral Sclerosis to Regain Control over Their Future: A Qualitative Study
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van Eenennaam, Remko M., primary, Koppenol, Loulou S., additional, Kruithof, Willeke J., additional, Kruitwagen-van Reenen, Esther T., additional, Pieters, Sotice, additional, van Es, Michael A., additional, van den Berg, Leonard H., additional, Visser-Meily, Johanna M. A., additional, and Beelen, Anita, additional
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- 2021
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22. A case of ALS with posterior cortical atrophy
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Nijboer, Tanja C.W., Nitert, Bram, Westeneng, Henk Jan, Van Den Berg, Leonard H., van Es, Michael A., Experimental Psychology (onderzoeksprogramma PF), Leerstoel Postma, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Leerstoel Postma, and Helmholtz Institute
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Pathology ,medicine.medical_specialty ,Neurology ,MND-FTD continuum ,Clinical Neurology ,posterior cortical atrophy ,Disease ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,Atrophy ,Humans ,Medicine ,Amyotrophic lateral sclerosis ,Aged ,business.industry ,Brain ,Posterior cortical atrophy ,medicine.disease ,Magnetic Resonance Imaging ,Clinical neurology ,Frontotemporal Dementia ,Disease Progression ,Female ,Neurology (clinical) ,medicine.symptom ,Cognition Disorders ,business ,030217 neurology & neurosurgery ,Frontotemporal dementia - Abstract
Here, we provide a case-report of an amyotrophic lateral sclerosis (ALS) patient with cognitive deficits best defined as posterior cortical atrophy (PCA). This is an unusual finding as ALS forms a spectrum with frontotemporal dementia (FTD), whereas PCA is predominantly associated with Alzheimer’s disease pathology. We hypothesize on whether ALS with PCA might be an under recognized phenotype considering multiple imaging studies in ALS have also reported (asymptomatic) parietal atrophy.
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- 2019
23. Incidence, Prevalence and Geographical Clustering of Motor Neuron Disease in the Netherlands
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de Jongh, Adriaan D, van Eijk, Ruben P A, Peters, Susan M, van Es, Michael A, Horemans, Anja M C, van der Kooi, Anneke J, Voermans, Nicol C, Vermeulen, Roel C H, Veldink, Jan H, van den Berg, Leonard H, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, IRAS OH Epidemiology Chemical Agents, and dIRAS RA-2
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0301 basic medicine ,Disease ,Article ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,All institutes and research themes of the Radboud University Medical Center ,Risk mapping ,Medicine ,Poisson regression ,Prospective cohort study ,business.industry ,Mortality rate ,Incidence (epidemiology) ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,Confidence interval ,030104 developmental biology ,symbols ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Demography ,Incidence prevalence - Abstract
ObjectiveTo assess time trends in motor neuron disease (MND) incidence, prevalence, and mortality and to investigate geographic clustering of MND cases in the Netherlands from 1998 to 2017, we analyzed data from the Netherlands Personal Records database, the Netherlands MND Center, and the Netherlands Patient Association of Neuromuscular Diseases.MethodsIn this prospective cohort study, Poisson regression was used to assess time trends in MND risk. We calculated age- and sex-standardized, observed, and expected cases for 1,694 areas. Bayesian smoothed risk mapping was used to investigate geographic MND risk.ResultsWe identified 7,992 MND cases, reflecting an incidence of 2.64 (95% confidence interval [CI] 2.62–2.67) per 100,000 person-years and a prevalence of 9.5 (95% CI 9.1–10.0) per 100,000 persons. Highest age-standardized prevalence and mortality rates occurred at a later age in men than in women (p < 0.001). Unadjusted mortality rates increased by 53.2% from 2.57 per 100,000 person-years in 1998 to 3.86 per 100,000 person-years in 2017. After adjustment for age and sex, an increase in MND mortality rate of 14.1% (95% CI 5.7%–23.2%, p < 0.001) remained. MND relative risk ranged from 0.78 to 1.43 between geographic areas; multiple urban and rural high-risk areas were identified.ConclusionsWe found a significant national increase in MND mortality from 1998 through 2017, explained only partly by an aging Dutch population, and a geographic variability in MND risk, suggesting a role for environmental or demographic risk factors.
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- 2021
24. Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
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van Rheenen, Wouter, van der Spek, Rick A A, Shireby, Gemma, Whiteman, David C, Olsen, Catherine M, Uitterlinden, Andre G, Hofman, Albert, Rietschel, Marcella, Cichon, Sven, Nöthen, Markus M., Amouyel, Philippe, Consortium, SLALOM, Consortium, PARALS, Hannon, Eilis, Consortium, SLAGEN, Consortium, SLAP, 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, Moisse, Matthieu, Grosskreutz, Julian, Roediger, Annekathrin, Gaur, Nayana, Jörk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Benjamin, Stubendorff, Beatrice, Witte, Otto W, Steinbach, Robert, Baird, Denis, Hübner, Christian A, Graff, Caroline, Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaž, Zidar, Janez, Ravnik-Glavač, Metka, Restuadi, Restuadi, Glavač, Damjan, Stević, Zorica, Drory, Vivian, Povedano, Monica, Blair, Ian P, Kiernan, Matthew C, Benyamin, Beben, Henderson, Robert D, Furlong, Sarah, Mathers, Susan, Dolzhenko, Egor, 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, Dekker, Annelot M, Henders, Anjali K, Wallace, Leanne, de Carvalho, Mamede, Pinto, Susana, Petri, Susanne, Weber, Markus, Rouleau, Guy A, Silani, Vincenzo, Curtis, Charles J, Breen, Gerome, Gawor, Klara, Glass, Jonathan D, Brown, 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, Westeneng, Henk-Jan, 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, Tazelaar, Gijs H P, Runz, Heiko, Franke, Lude, Al-Chalabi, Ammar, Van Damme, Philip, van den Berg, Leonard H, Veldink, Jan H, Comi, Giancarlo, Riva, Nilo, Lunetta, Christian, Gerardi, Francesca, Bakker, Mark K, van Eijk, Kristel R, Cotelli, Maria Sofia, Rinaldi, Fabrizio, Chiveri, Luca, Guaita, Maria Cristina, Perrone, Patrizia, Ceroni, Mauro, Diamanti, Luca, Ferrarese, Carlo, Tremolizzo, Lucio, Delodovici, Maria Luisa, Kooyman, Maarten, Bono, Giorgio, Canosa, Antonio, Manera, Umberto, Vasta, Rosario, Bombaci, Alessandro, Casale, Federico, Fuda, Giuseppe, Salamone, Paolina, Iazzolino, Barbara, Peotta, Laura, Byrne, Ross P, Cugnasco, Paolo, De Marco, Giovanni, Torrieri, Maria Claudia, Palumbo, Francesca, Gallone, Salvatore, Barberis, Marco, Sbaiz, Luca, Gentile, Salvatore, Mauro, Alessandro, Mazzini, Letizia, Doherty, Mark, De Marchi, Fabiola, Corrado, Lucia, D'Alfonso, Sandra, Bertolotto, Antonio, Gionco, Maurizio, Leotta, Daniela, Odddenino, Enrico, Imperiale, Daniele, Cavallo, Roberto, Pignatta, Pietro, Heverin, Mark, De Mattei, Marco, Geda, Claudio, Papurello, Diego Maria, Gusmaroli, Graziano, Comi, Cristoforo, Labate, Carmelo, Ruiz, Luigi, Ferrandi, Delfina, Rota, Eugenia, Aguggia, Marco, Al Khleifat, Ahmad, Di Vito, Nicoletta, Meineri, Piero, Ghiglione, Paolo, Launaro, Nicola, Dotta, Michele, Di Sapio, Alessia, Giardini, Guido, Tiloca, Cinzia, Peverelli, Silvia, Taroni, Franco, Iacoangeli, Alfredo, Pensato, Viviana, Castellotti, Barbara, Comi, Giacomo P, Del Bo, Roberto, Gagliardi, Stella, Raggi, Flavia, Simoncini, Costanza, Shatunov, Aleksey, Lo Gerfo, Annalisa, Inghilleri, Maurizio, Ferlini, Alessandra, Simone, Isabella L, Passarella, Bruno, Guerra, Vito, Zoccolella, Stefano, Nozzoli, Cecilia, Mundi, Ciro, Leone, Maurizio, Ticozzi, Nicola, Zarrelli, Michele, Tamma, Filippo, Valluzzi, Francesco, Calabrese, Gianluigi, Boero, Giovanni, Rini, Augusto, Cooper-Knock, Johnathan, van Vugt, Joke J F A, Smith, Bradley N, Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E, Shaw, Pamela J, Hardy, John, Orrell, Richard W, Sendtner, Michael, Meyer, Thomas, Hop, Paul J, Başak, Nazli, van der Kooi, Anneke J, Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, Zwamborn, Ramona A J, Sorarù, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chiò, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Grassano, Maurizio, de Klein, Niek, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H, Westra, Harm-Jan, Bell, Shaughn, Vourc'h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stéphanie, Meininger, Vincent, Salachas, François, Mora Pardina, Jesus S, Assialioui, Abdelilah, Rojas-García, Ricardo, Bakker, Olivier B, Dion, Patrick A, Ross, Jay P, Ludolph, Albert, Weishaupt, Jochen H, Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Dürr, Alexandra, Payan, Christine A M, Deelen, Patrick, Saker-Delye, Safa, Wood, Nicholas W, Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, and Kraft, Julia
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ddc:570 ,Genetics ,Medizin - Abstract
In the version of this article initially published, the affiliation for Nazli Başak appeared incorrectly. Nazli Başak is at Koç University, School of Medicine, KUTTAM-NDAL, Istanbul, Turkey, and not Bogazici University. The error has been corrected in the HTML and PDF versions of the article.
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- 2021
25. Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials
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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., van Es, Michael A, For UKMND-LiCALS and LITALS Study Group: Allen C, Counsell C, Farrin A, Al-Chalabi A, Dickie B, Kelly J, Leigh PN, Murphy CL, Payan C, Reynolds G, Shaw P, Steen IN, Thornhill M, Waters J, Zajicek J, Shaw PJ, Young CA, Morrison KE, Dhariwal S, Hornabrook R, Savage L, Burn DJ, Khoo TK, Dougherty A, Wijesekera L, Ellis CM, Ali R, O'Hanlon K, Panicker J, Pate L, Ray P, Wyatt L, Copeland L, Ealing J, Hamdalla H, Leroi I, Murphy C, O'Keeffe F, Oughton E, Partington L, Paterson P, Rog D, Sathish A, Sexton D, Smith J, Vanek H, Dodds S, Williams TL, Clarke J, Eziefula C, Howard R, Orrell R, Sidle K, Sylvester R, Barrett W, Merritt C, Talbot K, Turner MR, Whatley C, Williams C, Williams J, Cosby C, Hanemann CO, Imam I, Phillips C, Timings L, Crawford SE, Hewamadduma C, Hibberd R, Hollinger H, McDermott C, Mills G, Rafiq M, Taylor A, Waines E, Walsh T, Addison-Jones R, Birt J, Hare M, Majid T, Tortelli R, D'Errico E, Bartolomei I, Barbarossa E, Depau B, Costantino E, D'Amico E, Uncini A, Manzoli C, Quatrale R, Sette E, Montanari E, Merello M, Zarcone D, Mascolo M, Vignolo M, Messina S, Morelli C, Marinou K, Papetti L, Lunetta C, Gorni K, De Cicco D, Pipia C, Sola P, Georgoulopoulou E, Sagnelli A, Tedeschi, Gioacchino, Oggioni G, Nasuelli N, D'Ascenzo C, Cima V, Aiello M, Rizzi R, Rinaldi E, Luigetti M, Conte A, Torzini A, Greco G, Mutani R, Fuda G, Tommasi MA, 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., van Es, Michael A, For UKMND-LiCALS and LITALS Study Group: Allen, C, Counsell, C, Farrin, A, Al-Chalabi, A, Dickie, B, Kelly, J, Leigh, Pn, Murphy, Cl, Payan, C, Reynolds, G, Shaw, P, Steen, In, Thornhill, M, Waters, J, Zajicek, J, Shaw, Pj, Young, Ca, Morrison, Ke, Dhariwal, S, Hornabrook, R, Savage, L, Burn, Dj, Khoo, Tk, Dougherty, A, Wijesekera, L, Ellis, Cm, Ali, R, O'Hanlon, K, Panicker, J, Pate, L, Ray, P, Wyatt, L, Copeland, L, Ealing, J, Hamdalla, H, Leroi, I, Murphy, C, O'Keeffe, F, Oughton, E, Partington, L, Paterson, P, Rog, D, Sathish, A, Sexton, D, Smith, J, Vanek, H, Dodds, S, Williams, Tl, Clarke, J, Eziefula, C, Howard, R, Orrell, R, Sidle, K, Sylvester, R, Barrett, W, Merritt, C, Talbot, K, Turner, Mr, Whatley, C, Williams, C, Williams, J, Cosby, C, Hanemann, Co, Imam, I, Phillips, C, Timings, L, Crawford, Se, Hewamadduma, C, Hibberd, R, Hollinger, H, Mcdermott, C, Mills, G, Rafiq, M, Taylor, A, Waines, E, Walsh, T, Addison-Jones, R, Birt, J, Hare, M, Majid, T, Tortelli, R, D'Errico, E, Bartolomei, I, Barbarossa, E, Depau, B, Costantino, E, D'Amico, E, Uncini, A, Manzoli, C, Quatrale, R, Sette, E, Montanari, E, Merello, M, Zarcone, D, Mascolo, M, Vignolo, M, Messina, S, Morelli, C, Marinou, K, Papetti, L, Lunetta, C, Gorni, K, De Cicco, D, Pipia, C, Sola, P, Georgoulopoulou, E, Sagnelli, A, Tedeschi, Gioacchino, Oggioni, G, Nasuelli, N, D'Ascenzo, C, Cima, V, Aiello, M, Rizzi, R, Rinaldi, E, Luigetti, M, Conte, A, Torzini, A, Greco, G, Mutani, R, Fuda, G, and Tommasi, Ma
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Oncology ,R853.C55 ,medicine.medical_specialty ,Genotype ,Neuroprotective Agent ,Clinical Neurology ,Nerve Tissue Proteins ,Review ,Amyotrophic Lateral Sclerosis ,C9orf72 Protein ,Lithium Carbonate ,Neuroprotective Agents ,Proportional Hazards Models ,Proteins ,Pharmacogenetics ,Randomized Controlled Trials as Topic ,Neurology (clinical) ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Journal Article ,030212 general & internal medicine ,Amyotrophic lateral sclerosis ,business.industry ,Protein ,Pharmacogenetic ,medicine.disease ,Clinical trial ,RC0346 ,Meta-analysis ,Nerve Tissue Protein ,Proportional Hazards Model ,business ,030217 neurology & neurosurgery ,Meta-Analysis ,Amyotrophic Lateral Sclerosi - Abstract
OBJECTIVE\ud \ud To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders.\ud \ud METHODS\ud \ud Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months. On an exploratory basis, we assessed whether the effect of lithium depended on the genotype.\ud \ud RESULTS\ud \ud Clinical data were available for 518 of the 606 participants. Overall, treatment with lithium carbonate did not improve 12-month survival (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.7-1.4; p = 0.96). Both the UNC13A and C9orf72 genotype were independent predictors of survival (HR 2.4, 95% CI 1.3-4.3; p = 0.006 and HR 2.5, 95% CI 1.1-5.2; p = 0.032, respectively). The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3).\ud \ud CONCLUSIONS\ud \ud This study incorporated genetic data into past ALS trials to determine treatment effects in a genetic post hoc analysis. Our results suggest that we should reorient our strategies toward finding treatments for ALS, start focusing on genotype-targeted treatments, and standardize genotyping in order to optimize randomization and analysis for future clinical trials.
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- 2017
26. A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis
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Fogh, Isabella, Ratti, Antonia, Gellera, Cinzia, Lin, Kuang, Tiloca, Cinzia, Moskvina, Valentina, Corrado, Lucia, Sorarù, Gianni, Cereda, Cristina, Corti, Stefania, Gentilini, Davide, Calini, Daniela, Castellotti, Barbara, Mazzini, Letizia, Querin, Giorgia, Gagliardi, Stella, Del Bo, Roberto, Conforti, Francesca L., Siciliano, Gabriele, Inghilleri, Maurizio, Saccà, Francesco, Bongioanni, Paolo, Penco, Silvana, Corbo, Massimo, Sorbi, Sandro, Filosto, Massimiliano, Ferlini, Alessandra, Di Blasio, Anna M., Signorini, Stefano, Shatunov, Aleksey, Jones, Ashley, Shaw, Pamela J., Morrison, Karen E., Farmer, Anne E., Van Damme, Philip, Robberecht, Wim, Chiò, Adriano, Traynor, Bryan J., Sendtner, Michael, Melki, Judith, Meininger, Vincent, Hardiman, Orla, Andersen, Peter M., Leigh, Nigel P., Glass, Jonathan D., Overste, Daniel, Diekstra, Frank P., Veldink, Jan H., van Es, Michael A., Shaw, Christopher E., Weale, Michael E., Lewis, Cathryn M., Williams, Julie, Brown, Robert H., Landers, John E., Ticozzi, Nicola, Ceroni, Mauro, Pegoraro, Elena, Comi, Giacomo P., DʼAlfonso, Sandra, van den Berg, Leonard H., Taroni, Franco, Al-Chalabi, Ammar, Powell, John, Silani, Vincenzo, Brescia Morra, Vincenzo, Filla, Alessandro, Massimo, Filosto, Marsili, Angela, Viviana, Pensato, Puorro, Giorgia, La Bella, Vincenzo, Logroscino, Giancarlo, Monsurrò, Maria Rosaria, Quattrone, Aldo, Simone, Isabella Laura, Ahmeti, Kreshnik B., Ajroud-Driss, Senda, Armstrong, Jennifer, Birve, Anne, Blauw, Hylke M., Bruijn, Lucie, Chen, Wenjie, Comeau, Mary C., Cronin, Simon, Soraya, Gkazi Athina, Grab, Josh D., Groen, Ewout J., Haines, Jonathan L., Heller, Scott, Huang, Jie, Hung, Wu-Yen, Jaworski, James M., Khan, Humaira, Langefeld, Carl D., Marion, Miranda C., McLaughlin, Russell L., Miller, Jack W., Mora, Gabriele, Pericak-Vance, Margaret A., Rampersaud, Evadnie, Siddique, Nailah, Siddique, Teepu, Smith, Bradley N., Sufit, Robert, Topp, Simon, Vance, Caroline, van Vught, Paul, Yang, Yi, and Zheng, J.G.
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- 2014
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27. Is it accurate to classify ALS as a neuromuscular disorder?
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van Es, Michael A, Goedee, H Stephan, Westeneng, Henk-Jan, Nijboer, Tanja C W, van den Berg, Leonard H, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Leerstoel Postma, Afd Psychologische functieleer, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Leerstoel Postma, and Afd Psychologische functieleer
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business.industry ,TDP-43 ,General Neuroscience ,Amyotrophic lateral sclerosis(ALS) ,Neurodegeneration ,Amyotrophic Lateral Sclerosis ,neurodegeneration ,Neurodegenerative Diseases ,Neuromuscular Diseases ,medicine.disease ,frontotemporaldementia (FTD) ,030227 psychiatry ,Domain (software engineering) ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Pharmacology (medical) ,Neurology (clinical) ,Amyotrophic lateral sclerosis ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal disorder characterized by the progressive loss of upper and lower motor neurons. ALS has traditionally been classified within the domain of neuromuscular diseases, which are a unique spectrum of disorders that predominantly affect the peripheral nervous system. However, over the past decades compounding evidence has emerged that there is extensive involvement of the central nervous system. Therefore, one can question whether it remains accurate to classify ALS as a neuromuscular disorder. AREAS COVERED: In this review, the authors sought to discuss current approaches toward disease classification and how we should classify ALS based on novel insights from clinical, imaging, pathophysiological, neuropathological and genetic studies. EXPERT OPINION: ALS exhibits the cardinal features of a neurodegenerative disease. Therefore, classifying ALS as a neuromuscular disease in the strict sense has become untenable. Diagnosing ALS however does require significant neuromuscular expertise and therefore neuromuscular specialists remain best equipped to evaluate this category of patients. Designating motor neuron diseases as a separate category in the ICD-11 is justified and adequately deals with this issue. However, to drive effective therapy development the fields of motor neuron disease and neurodegenerative disorders must come together.
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- 2020
28. Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy
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Schijven, D., Stevelink, R., Mccormack, M., van Rheenen, W., Luykx, J. J., Koeleman, B. P. C., Veldink, J. H., Aleksey, Shatunov, Mclaughlin, Russell L., van der Spek, Rick A. A., Alfredo, Iacoangeli, Kenna, Kevin P., van Eijk, Kristel R., Nicola, Ticozzi, Boris, Rogelj, Katarina, Vrabec, Metka, Ravnik-Glavač, Blaž, Koritnik, Janez, Zidar, Lea, Leonardis, Leja Dolenc Grošelj, Stéphanie, Millecamps, François, Salachas, Vincent, Meininger, Mamede de Carvalho, Susana, Pinto, Marta, Gromicho, Ana, Pronto-Laborinho, Mora, Jesus S., Ricardo, Rojas-García, Meraida, Polak, Siddharthan, Chandran, Shuna, Colville, Robert, Swingler, Morrison, Karen E., Shaw, Pamela J., John, Hardy, Orrell, Richard W., Alan, Pittman, Katie, Sidle, Pietro, Fratta, Andrea, Malaspina, Simon, Topp, Susanne, Petri, Susanna, Abdulla, Carsten, Drepper, Michael, Sendtner, Thomas, Meyer, Ophoff, Roel A., Staats, Kim A., Martina, Wiedau-Pazos, Catherine, Lomen-Hoerth, Van Deerlin, Vivianna M., Trojanowski, John Q., Lauren, Elman, Leo, Mccluskey, Nazli Basak, A., Thomas, Meitinger, Peter, Lichtner, Milena, Blagojevic-Radivojkov, Andres, Christian R., Gilbert, Bensimon, Bernhard, Landwehrmeyer, Alexis, Brice, Payan, Christine A. M., Safaa, Saker-Delye, Alexandra, Dürr, Wood, Nicholas W., Lukas, Tittmann, Wolfgang, Lieb, Andre, Franke, Marcella, Rietschel, Sven, Cichon, Nöthen, Markus M., Philippe, Amouyel, Christophe, Tzourio, Jean-François, Dartigues, Uitterlinden, Andre G., Fernando, Rivadeneira, Karol, Estrada, Albert, Hofman, Charles, Curtis, van der Kooi, Anneke J., Markus, Weber, Shaw, Christopher E., Smith, Bradley N., Daisy, Sproviero, Cristina, Cereda, Mauro, Ceroni, Luca, Diamanti, Roberto Del Bo, Stefania, Corti, Comi, Giacomo P., Sandra, D'Alfonso, Lucia, Corrado, Bertolin, Cinzia, Soraru', Gianni, Letizia, Mazzini, Viviana, Pensato, Cinzia, Gellera, Cinzia, Tiloca, Antonia, Ratti, Andrea, Calvo, Cristina, Moglia, Maura, Brunetti, Simona, Arcuti, Rosa, Capozzo, Chiara, Zecca, Christian, Lunetta, Silvana, Penco, Nilo, Riva, Alessandro, Padovani, Massimiliano, Filosto, Ian, Blair, Nicholson, Garth A., Rowe, Dominic B., Roger, Pamphlett, Kiernan, Matthew C., Julian, Grosskreutz, Witte, Otto W., Robert, Steinbach, Tino, Prell, Beatrice, Stubendorff, Ingo, Kurth, Hübner, Christian A., Nigel Leigh, P., Federico, Casale, Adriano, Chio, Ettore, Beghi, Elisabetta, Pupillo, Rosanna, Tortelli, Giancarlo, Logroscino, John, Powell, Ludolph, Albert C., Weishaupt, Jochen H., Wim, Robberecht, Philip Van Damme, Brown, Robert H., Glass, Jonathan D., Landers, John E., Orla, Hardiman, Andersen, Peter M., Philippe, Corcia, Patrick, Vourc'H, Vincenzo, Silani, van Es, Michael A., Jeroen Pasterkamp, R., Lewis, Cathryn M., Gerome, Breen, Ammar, Al-Chalabi, van den Berg, Leonard H., Veldink, Jan H., Daniela, Calini, Isabella, Fogh, Barbara, Castellotti, Franco, Taroni, Stella, Gagliardi, Giacomo, Comi, Sandra, D’Alfonso, Pegoraro, Elena, Giorgia, Querin, Francesca, Gerardi, Fabrizio, Rinaldi, Maria Sofia Cotelli, Luca, Chiveri, Maria Cristina Guaita, Patrizia, Perrone, Giancarlo, Comi, Carlo, Ferrarese, Lucio, Tremolizzo, Marialuisa, Delodovici, Giorgio, Bono, Stefania, Cammarosano, Antonio, Canosa, Dario, Cocito, Leonardo, Lopiano, Luca, Durelli, Bruno, Ferrero, Antonio, Bertolotto, Alessandro, Mauro, Luca, Pradotto, Roberto, Cantello, Enrica, Bersano, Dario, Giobbe, Maurizio, Gionco, Daniela, Leotta, Lucia, Appendino, Cavallo, Cavallo, Enrico, Odddenino, Claudio, Geda, Fabio, Poglio, Paola, Santimaria, Umberto, Massazza, Antonio, Villani, Roberto, Conti, Fabrizio, Pisano, Mario, Palermo, Franco, Vergnano, Paolo, Provera, Maria Teresa Penza, Marco, Aguggia, Nicoletta Di Vito, Piero, Meineri, Ilaria, Pastore, Paolo, Ghiglione, Danilo, Seliak, Nicola, Launaro, Giovanni, Astegiano, Bottacchi, Edo, Isabella Laura Simone, Stefano, Zoccolella, Michele, Zarrelli, Franco, Apollo, William, Camu, Jean Sebastien Hulot, Francois, Viallet, Philippe, Couratier, David, Maltete, Christine, Tranchant, Marie, Vidailhet, Bassel, Abou-Khalil, Pauls, Auce, Andreja, Avbersek, Melanie, Bahlo, David, J Balding, Thomas, Bast, Larry, Baum, Albert, J Becker, Felicitas, Becker, Bianca, Berghuis, Samuel, F Berkovic, Katja, E Boysen, Jonathan, P Bradfield, Lawrence, C Brody, Russell, J Buono, Ellen, Campbell, Gregory, D Cascino, Claudia, B Catarino, Gianpiero, L Cavalleri, Stacey, S Cherny, Krishna, Chinthapalli, Alison, J Coffey, Alastair, Compston, Antonietta, Coppola, Patrick, Cossette, John, J Craig, Gerrit-Jan de Haan, Peter De Jonghe, Carolien G, F de Kovel, Norman, Delanty, Chantal, Depondt, Orrin, Devinsky, Dennis, J Dlugos, Colin, P Doherty, Christian, E Elger, Johan, G Eriksson, Thomas, N Ferraro, Martha, Feucht, Ben, Francis, Jacqueline, A French, Saskia, Freytag, Verena, Gaus, Eric, B Geller, Christian, Gieger, Tracy, Glauser, Simon, Glynn, David, B Goldstein, Hongsheng, Gui, Youling, Guo, Kevin, F Haas, Hakon, Hakonarson, Kerstin, Hallmann, Sheryl, Haut, Erin, L Heinzen, Ingo, Helbig, Christian, Hengsbach, Helle, Hjalgrim, Michele, Iacomino, Andrés, Ingason, Michael, R Johnson, Reetta, Kälviäinen, Anne-Mari, Kantanen, Dalia, Kasperavičiūte, Dorothee Kasteleijn-Nolst Trenite, Heidi, E Kirsch, Robert, C Knowlton, Bobby P, C Koeleman, Roland, Krause, Martin, Krenn, Wolfram, S Kunz, Ruben, Kuzniecky, Patrick, Kwan, Dennis, Lal, Yu-Lung, Lau, Anna-Elina, Lehesjoki, Holger, Lerche, Costin, Leu, Dick, Lindhout, Warren, D Lo, Iscia, Lopes-Cendes, Daniel, H Lowenstein, Alberto, Malovini, Anthony, G Marson, Thomas, Mayer, Mark, Mccormack, James, L Mills, Nasir, Mirza, Martina, Moerzinger, Rikke, S Møller, Anne, M Molloy, Hiltrud, Muhle, Mark, Newton, Ping-Wing, Ng, Markus, M Nöthen, Peter, Nürnberg, Terence, J O’Brien, Karen, L Oliver, Aarno, Palotie, Faith, Pangilinan, Sarah, Peter, Slavé, Petrovski, Annapurna, Poduri, Michael, Privitera, Rodney, Radtke, Sarah, Rau, Philipp, S Reif, Eva, M Reinthaler, Felix, Rosenow, Josemir, W Sander, Thomas, Sander, Theresa, Scattergood, Steven, C Schachter, Christoph, J Schankin, Ingrid, E Scheffer, Bettina, Schmitz, Susanne, Schoch, Pak, C Sham, Jerry, J Shih, Graeme, J Sills, Sanjay, M Sisodiya, Lisa, Slattery, Alexander, Smith, David, F Smith, Michael, C Smith, Philip, E Smith, Anja C, M Sonsma, Doug, Speed, Michael, R Sperling, Bernhard, J Steinhoff, Ulrich, Stephani, Remi, Stevelink, Konstantin, Strauch, Pasquale, Striano, Hans, Stroink, Rainer, Surges, K Meng Tan, Liu Lin Thio, G Neil Thomas, Marian, Todaro, Rossana, Tozzi, Maria, S Vari, Eileen P, G Vining, Frank, Visscher, Sarah von Spiczak, Nicole, M Walley, Yvonne, G Weber, Zhi, Wei, Judith, Weisenberg, Christopher, D Whelan, Peter, Widdess-Walsh, Markus, Wolff, Stefan, Wolking, Wanling, Yang, Federico, Zara, Fritz, Zimprich, Project MinE ALS GWAS Consortium, International League Against Epilepsy Consortium on Complex Epilepsies, Department of Medical and Clinical Genetics, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, Clinicum, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, and HUS Helsinki and Uusimaa Hospital District
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Risk ,0301 basic medicine ,Aging ,Genetic correlation ,Geriatrics & Gerontology ,education ,Genome-wide association study ,Biology ,ALS ,Epilepsy ,Amyotrophic Lateral Sclerosis ,Gene Frequency ,Humans ,Genetic Variation ,Genome-Wide Association Study ,Negative Results ,Article ,3124 Neurology and psychiatry ,03 medical and health sciences ,0302 clinical medicine ,Genetic variation ,medicine ,Amyotrophic lateral sclerosis ,Allele frequency ,Genetics ,Science & Technology ,Mechanism (biology) ,General Neuroscience ,3112 Neurosciences ,Neurosciences ,medicine.disease ,3. Good health ,Minor allele frequency ,030104 developmental biology ,Neurology (clinical) ,Neurosciences & Neurology ,Geriatrics and Gerontology ,Life Sciences & Biomedicine ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins. ispartof: NEUROBIOLOGY OF AGING vol:92 ispartof: location:United States status: published
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- 2020
29. ATXN1 repeat expansions confer risk for amyotrophic lateral sclerosis and contribute to TDP-43 mislocalization
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Tazelaar, Gijs, Boeynaems, Steven, De Decker, Mathias, van Vugt, Joke, Kool, Lindy, Goedee, H Stephan, Mclaughlin, Russell, Sproviero, William, Iacoangeli, Alfredo, Moisse, Matthieu, Jacquemyn, Maarten, Daelemans, Dirk, Dekker, Annelot, van der Spek, Rick, Westeneng, Henk-Jan, Kenna, Kevin, Assialioui, Abdelilah, Da Silva, Nica, Millecamps, Stéphanie, Akçimen, Fulya, Al Khleifat, Ahmad, Al-Chalabi, Ammar, Andersen, Peter, Basak, A Nazli, Bauer, Denis, Blair, Ian, Brands, William, Byrne, Ross, Calvo, Andrea, Gonzalez, Yolanda Campos, Chio, Adriano, Cooper-Knock, Jonothan, Corcia, Philippe, Couratier, Philippe, De Carvalho, Mamede, Drory, Vivian, Eitan, Chen, Redondo, Alberto Garcia, Gellera, Cinzia, Glass, Jonathan, Gotkine, Marc, Hardiman, Orla, Hornstein, Eran, Kenna, Brandon, Kiernan, Matthew, Kocoglu, Cemile, Kooyman, Maarten, Landers, John, Alonso, Victoria López, Middelkoop, Bas, Mill, Jonathan, Mitne-Neto, Miguel, Mora Pardina, Jesus, Morrison, Karen, Pinto, Susana, Gromicho, Marta, Panadés, Monica Povedano, Pulit, Sara, Ratti, Antonia, Robberecht, Wim, Schellevis, Raymond, Shatunov, Aleksey, Shaw, Christopher, Shaw, Pamela, Silani, Vincenzo, Staiger, Christine, Ticozzi, Nicola, Tunca, Ceren, Twine, Nathalie, Van Damme, Philip, van den Berg, Leonard, van Doormaal, Perry, van Eijk, Kristel, van Es, Michael, van Rheenen, Wouter, Veldink, Jan, Visscher, Peter, Vourc’h, Patrick, Weber, Markus, Williams, Kelly, Wray, Naomi, Yang, Jian, Zatz, Mayana, Zhang, Katharine, Povedano, Mónica, Pardina, Jesus, Salachas, François, Pasterkamp, R Jeroen, Van Den Bosch, Ludo, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,Spinocerebellar Ataxia Type 1 ,amyotrophic lateral sclerosis ,Protein TDP-43 ,Disease Association ,Biology ,[SCCO]Cognitive science ,03 medical and health sciences ,0302 clinical medicine ,C9orf72 ,medicine ,Genetics ,trinucleotide repeat expansions ,Amyotrophic lateral sclerosis ,ComputingMilieux_MISCELLANEOUS ,AcademicSubjects/SCI01870 ,[SCCO.NEUR]Cognitive science/Neuroscience ,General Engineering ,DNA Repeat Expansion ,medicine.disease ,Phenotype ,030104 developmental biology ,DNA repeat expansion ,genetic association study ,Original Article ,AcademicSubjects/MED00310 ,Trinucleotide repeat expansion ,030217 neurology & neurosurgery ,Esclerosi lateral amiotròfica ,Genètica - Abstract
Increasingly, repeat expansions are being identified as part of the complex genetic architecture of amyotrophic lateral sclerosis. To date, several repeat expansions have been genetically associated with the disease: intronic repeat expansions in C9orf72, polyglutamine expansions in ATXN2 and polyalanine expansions in NIPA1. Together with previously published data, the identification of an amyotrophic lateral sclerosis patient with a family history of spinocerebellar ataxia type 1, caused by polyglutamine expansions in ATXN1, suggested a similar disease association for the repeat expansion in ATXN1. We, therefore, performed a large-scale international study in 11 700 individuals, in which we showed a significant association between intermediate ATXN1 repeat expansions and amyotrophic lateral sclerosis (P = 3.33 × 10−7). Subsequent functional experiments have shown that ATXN1 reduces the nucleocytoplasmic ratio of TDP-43 and enhances amyotrophic lateral sclerosis phenotypes in Drosophila, further emphasizing the role of polyglutamine repeat expansions in the pathophysiology of amyotrophic lateral sclerosis., Repeat expansions are being identified as part of the complex genetic architecture of amyotrophic lateral sclerosis. This study shows a significant association between intermediate ATXN1 repeat expansions and amyotrophic lateral sclerosis, possibly via mislocalization of TDP-43, further emphasizing the role of polyglutamine expansions in the pathophysiology of amyotrophic lateral sclerosis., Graphical Abstract Graphical Abstract
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- 2020
30. Evidence for an oligogenic basis of amyotrophic lateral sclerosis
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van Blitterswijk, Marka, van Es, Michael A., Hennekam, Eric A.M., Dooijes, Dennis, van Rheenen, Wouter, Medic, Jelena, Bourque, Pierre R., Schelhaas, Helenius J., van der Kooi, Anneke J., de Visser, Marianne, de Bakker, Paul I.W., Veldink, Jan H., and van den Berg, Leonard H.
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- 2012
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31. Facial Onset Sensory and Motor Neuronopathy
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de Boer, Eva M.J., primary, Barritt, Andrew W., additional, Elamin, Marwa, additional, Anderson, Stuart J., additional, Broad, Rebecca, additional, Nisbet, Angus, additional, Goedee, H. Stephan, additional, Vázquez Costa, Juan F., additional, Prudlo, Johannes, additional, Vedeler, Christian A., additional, Fernandez, Julio Pardo, additional, Panades, Mónica Povedano, additional, Albertí Aguilo, Maria A., additional, Bella, Eleonora Dalla, additional, Lauria, Giuseppe, additional, Pinto, Wladimir B.V.R., additional, de Souza, Paulo V.S., additional, Oliveira, Acary S.B., additional, Toro, Camilo, additional, van Iersel, Joost, additional, Parson, Malu, additional, Harschnitz, Oliver, additional, van den Berg, Leonard H., additional, Veldink, Jan H., additional, Al-Chalabi, Ammar, additional, Leigh, Peter N., additional, and van Es, Michael A., additional
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- 2020
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32. 5′ValCAC tRNA fragment generated as part of a protective angiogenin response provides prognostic value in amyotrophic lateral sclerosis
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Hogg, Marion C, primary, Rayner, Megan, additional, Susdalzew, Sergej, additional, Monsefi, Naser, additional, Crivello, Martin, additional, Woods, Ina, additional, Resler, Alexa, additional, Blackbourn, Lisle, additional, Fabbrizio, Paola, additional, Trolese, Maria Chiara, additional, Nardo, Giovanni, additional, Bendotti, Caterina, additional, van den Berg, Leonard H, additional, van Es, Michael A, additional, and Prehn, Jochen H M, additional
- Published
- 2020
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33. A large genome scan for rare CNVs in amyotrophic lateral sclerosis
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Blauw, Hylke M., Al-Chalabi, Ammar, Andersen, Peter M., van Vught, Paul W.J., Diekstra, Frank P., van Es, Michael A., Saris, Christiaan G.J., Groen, Ewout J.N., van Rheenen, Wouter, Koppers, Max, vanʼt Slot, Ruben, Strengman, Eric, Estrada, Karol, Rivadeneira, Fernando, Hofman, Albert, Uitterlinden, Andre G., Kiemeney, Lambertus A., Vermeulen, Sita H.M., Birve, Anna, Waibel, Stefan, Meyer, Thomas, Cronin, Simon, McLaughlin, Russell L., Hardiman, Orla, Sapp, Peter C., Tobin, Martin D., Wain, Louise V., Tomik, Barbara, Slowik, Agnieszka, Lemmens, Robin, Rujescu, Dan, Schulte, Claudia, Gasser, Thomas, Brown, Robert H., Jr, Landers, John E., Robberecht, Wim, Ludolph, Albert C., Ophoff, Roel A., Veldink, Jan H., and van den Berg, Leonard H.
- Published
- 2010
- Full Text
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34. Genome-wide association study in premature ovarian failure patients suggests ADAMTS19 as a possible candidate gene
- Author
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Knauff, Erik A.H., Franke, Lude, van Es, Michael A., van den Berg, Leonard H., van der Schouw, Yvonne T., Laven, Joop S.E., Lambalk, Cornelius B., Hoek, Annemieke, Goverde, Angelique J., Christin-Maitre, Sophie, Hsueh, Aaron J., Wijmenga, Cisca, and Fauser, Bart C.J.M.
- Published
- 2009
35. Analysis of genome-wide copy number variation in Irish and Dutch ALS populations
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Cronin, Simon, Blauw, Hylke M., Veldink, Jan H., van Es, Michael A., Ophoff, Roel A., Bradley, Daniel G., van den Berg, Leonard H., and Hardiman, Orla
- Published
- 2008
36. A neuropsychological and behavioral study of PLS
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de Vries, Bálint S., Spreij, Lauriane A., Rustemeijer, Laura M.M., Bakker, Leonhard A., Veldink, Jan H., van den Berg, Leonard H., Nijboer, Tanja C.W., van Es, Michael, Leerstoel Postma, Experimental Psychology (onderzoeksprogramma PF), Helmholtz Institute, Afd Psychologische functieleer, Leerstoel Postma, Experimental Psychology (onderzoeksprogramma PF), Helmholtz Institute, and Afd Psychologische functieleer
- Subjects
Male ,cognition ,medicine.medical_specialty ,Neurology ,Theory of Mind ,Clinical Neurology ,Audiology ,Neuropsychological Tests ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Social cognition ,Primary lateral sclerosis ,Theory of mind ,medicine ,Journal Article ,Humans ,Amyotrophic lateral sclerosis ,Motor Neuron Disease ,Social Behavior ,neuropsychological evaluation ,Aged ,Aged, 80 and over ,Neuropsychology ,Cognition ,FTD ,Middle Aged ,Executive functions ,medicine.disease ,Female ,Neurology (clinical) ,Psychology ,030217 neurology & neurosurgery ,Frontotemporal dementia - Abstract
Background: Primary lateral sclerosis (PLS) is a rare motor neuron disease characterized by progressive degeneration of upper motor neurons, resulting in spasticity and disability. There is, however, mounting evidence that the disease is not limited to upper motor neurons alone and that cognitive and behavioral changes within the spectrum of frontotemporal dementia (FTD) are part of the clinical phenotype. Objectives: To provide an in-depth classification of the cognitive and behavioral profiles of PLS by using the golden standard, a full neuropsychological evaluation, as well as a comprehensive behavioral assessment in a cohort of 30 cases. Results: Only 7 out of 30 PLS patients scored within normal range on all of the tests within our battery. The neuropsychological profile of PLS consists of deficits in social cognition (affective theory of mind (ToM) in particular), fluency, executive functions and memory. Using the revised Strong criteria, we could classify 57% of patients within the FTD spectrum (of which 17% had behavioral variant FTD). An additional 20% of patients had deficits which were not characteristic of FTD. Conclusions: This study confirms that PLS is not a restricted phenotype (only affecting upper motor neurons) and that behavioral and cognitive changes are common. Therefore, clinicians treating PLS patients should routinely assess cognition and behavior as part of routine care as cognitive and behavioral changes impact management, decision-making and care-giver burden. This assessment should be sensitive to the neuropsychological profile of PLS (social cognition (affective ToM in particular), fluency, executive functions and memory) and behavioral changes.
- Published
- 2019
37. Association of NIPA1 repeat expansions with amyotrophic lateral sclerosis in a large international cohort
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Tazelaar, Gij SHP, Dekker, Annelot M, van Vugt, Joke JFA, van der Spek, Rick A, Westeneng, Henk-Jan, Kool, Lindy JBG, Kenna, Kevin P, van Rheenen, Wouter, Pulit, Sara L, McLaughlin, Russell L, Sproviero, William, Iacoangeli, Alfredo, Huebers, Annemarie, Brenner, David, Morrison, Karen E, Shaw, Pamela J, Shaw, Christopher E, Povedano Panades, Monica, 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, van Es, Michael A, Akcimen, Fulya, Al Khleifat, Ahmad, Andersen, Peter, Basak, A Nazli, Bauer, Denis C, Blair, Ian, Brands, William J, Byrne, Ross P, Calvo, Andrea, Gonzalez, Yolanda Campos, Chio, Adriano, Cooper-Knock, Jonothan, Corcia, Philippe, Couratier, Philippe, de Carvalho, Mamede, Drory, Vivian E, Eitan, Chen, Garcia Redondo, Alberto, Gellera, Cinzia, Gotkine, Marc, Hornstein, Eran, Kenna, Brendan, Kiernan, Matthew C, Kocoglu, Cemile, Kooyman, Maarten, Lopez Alonso, Victoria, Middelkoop, Bas, Mill, Jonathan, Mitne-Neto, Miguel, Moisse, Matthieu, Pinto, Susana C, Ratti, Antonia, Schellevis, Raymond D, Shatunov, Aleksey, Silani, Vincenzo, Staiger, Christine, Tazelaar, Gijs HP, Ticozzi, Nicola, Tunca, Ceren, Twine, Nathalie A, van Doormaal, Perry TC, van Eijk, Kristel R, Visscher, Peter M, Vourch, Patrick, Weber, Markus, Williams, Kelly L, Wray, Naomi, Yang, Jian, Zatz, Mayana, and Zhang, Katharine
- Subjects
0301 basic medicine ,Oncology ,Male ,Aging ,Geriatrics & Gerontology ,Internationality ,Cohort Studies ,0302 clinical medicine ,Copy-number variation ,Amyotrophic lateral sclerosis ,Non-U.S. Gov't ,DNA Repeat Expansion ,General Neuroscience ,Research Support, Non-U.S. Gov't ,Amyotrophic Lateral Sclerosis/genetics ,GENOME ,Cohort ,Female ,Life Sciences & Biomedicine ,Cohort study ,medicine.medical_specialty ,Hereditary spastic paraplegia ,Neuroscience(all) ,NIPA1 ,Clinical Neurology ,HEREDITARY SPASTIC PARAPLEGIA ,Research Support ,Article ,03 medical and health sciences ,DNA Repeat Expansion/genetics ,Meta-Analysis as Topic ,Internal medicine ,Angelman syndrome ,medicine ,Journal Article ,Humans ,Membrane Proteins/genetics ,Genetic Association Studies ,Science & Technology ,business.industry ,Neurosciences ,Membrane Proteins ,Repeat expansion ,medicine.disease ,Ageing ,030104 developmental biology ,Logistic Models ,Neurosciences & Neurology ,Neurology (clinical) ,Geriatrics and Gerontology ,Peptides ,business ,Trinucleotide repeat expansion ,Peptides/genetics ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
NIPA1 (nonimprinted in Prader-Willi/Angelman syndrome 1) mutations are known to cause hereditary spastic paraplegia type 6, a neurodegenerative disease that phenotypically overlaps to some extent with amyotrophic lateral sclerosis (ALS). Previously, a genomewide screen for copy number variants found an association with rare deletions in NIPA1 and ALS, and subsequent genetic analyses revealed that long (or expanded) polyalanine repeats in NIPA1 convey increased ALS susceptibility. We set out to perform a large-scale replication study to further investigate the role of NIPA1 polyalanine expansions with ALS, in which we characterized NIPA1 repeat size in an independent international cohort of 3955 patients with ALS and 2276 unaffected controls and combined our results with previous reports. Meta-analysis on a total of 6245 patients with ALS and 5051 controls showed an overall increased risk of ALS in those with expanded (>8) GCG repeat length (odds ratio = 1.50, p = 3.8×10-5). Together with previous reports, these findings provide evidence for an association of an expanded polyalanine repeat in NIPA1 and ALS. ispartof: NEUROBIOLOGY OF AGING vol:74 ispartof: location:United States status: published
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- 2019
38. Cognitive and behavioural changes in PLS and PMA:challenging the concept of restricted phenotypes
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De Vries, Bálint S., Rustemeijer, Laura M.M., Bakker, Leonhard A., Schröder, Carin D., Veldink, Jan H., Van Den Berg, Leonard H., Nijboer, Tanja C.W., Van Es, Michael, Leerstoel Postma, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Afd Psychologische functieleer, Leerstoel Postma, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), and Afd Psychologische functieleer
- Subjects
Male ,Adult ,medicine.medical_specialty ,Cognitive Dysfunction/diagnosis ,Clinical Neurology ,Neuropsychological Tests ,Research Support ,Muscular Atrophy, Spinal ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,80 and over ,medicine ,Journal Article ,Dementia ,Humans ,Cognitive Dysfunction ,Muscular Atrophy, Spinal/psychology ,Amyotrophic lateral sclerosis ,Motor Neuron Disease ,Non-U.S. Gov't ,Primary Lateral Sclerosis ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Mental Disorders ,Research Support, Non-U.S. Gov't ,Amyotrophic Lateral Sclerosis ,Cognition ,Retrospective cohort study ,Motor Neuron Disease/psychology ,Progressive muscular atrophy ,Middle Aged ,medicine.disease ,Muscular Atrophy ,Psychiatry and Mental health ,Spinal/psychology ,Phenotype ,Amyotrophic Lateral Sclerosis/diagnosis ,Anxiety ,Female ,Surgery ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Mental Disorders/epidemiology ,Frontotemporal dementia - Abstract
ObjectivesCognitive and behavioural changes within the spectrum of frontotemporal dementia (FTD) are observed frequently in patients with amyotrophic lateral sclerosis (ALS). Whether these changes also occur in other forms of motor neuron disease (MND) is not well studied. We therefore systemically screened a large cohort of patients with primary lateral sclerosis (PLS) and progressive muscular atrophy (PMA) for cognitive and behavioural changes, and subsequently compared our findings with a cohort of patients with ALS.MethodsUsing a set of screening instruments (Edinburgh Cognitive and Behavioural ALS Screen, ALS and Frontotemporal Dementia Questionnaire, Frontal Assessment Battery, and Hospital Anxiety and Depression Scale), the presence of cognitive and behavioural changes as well as anxiety and depression in 277 patients with ALS, 75 patients with PLS and 143 patients with PMA was evaluated retrospectively.ResultsWe found a high frequency of cognitive and behavioural abnormalities with similar profiles in all three groups. Subjects with behavioural variant FTD were identified in all groups.ConclusionsThe percentage of patients with PLS and PMA with cognitive dysfunction was similar to patients with ALS, emphasising the importance for cognitive screening as part of routine clinical care in all three patient groups. With a similar cognitive profile, in line with genetic and clinical overlap between the MNDs, the view of PLS as an MND exclusively affecting upper motor neurons and PMA exclusively affecting lower motor neurons cannot be held. Therefore, our findings are in contrast to the recently revised El Escorial criteria of 2015, where PLS and PMA are described as restricted phenotypes. Our study favours a view of PLS and PMA as multidomain diseases similar to ALS.
- Published
- 2019
39. KIF1A variants are a frequent cause of autosomal dominant hereditary spastic paraplegia
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Pennings, Maartje, primary, Schouten, Meyke I., additional, van Gaalen, Judith, additional, Meijer, Rowdy P. P., additional, de Bot, Susanne T., additional, Kriek, Marjolein, additional, Saris, Christiaan G. J., additional, van den Berg, Leonard H., additional, van Es, Michael A., additional, Zuidgeest, Dick M. H., additional, Elting, Mariet W., additional, van de Kamp, Jiddeke M., additional, van Spaendonck-Zwarts, Karin Y., additional, Die-Smulders, Christine de, additional, Brilstra, Eva H., additional, Verschuuren, Corien C., additional, de Vries, Bert B. A., additional, Bruijn, Jacques, additional, Sofou, Kalliopi, additional, Duijkers, Floor A., additional, Jaeger, B., additional, Schieving, Jolanda H., additional, van de Warrenburg, Bart P., additional, and Kamsteeg, Erik-Jan, additional
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- 2019
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40. Cross-sectional and longitudinal assessment of the upper cervical spinal cord in motor neuron disease
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van der Burgh, Hannelore K., primary, Westeneng, Henk-Jan, additional, Meier, Jil M., additional, van Es, Michael A., additional, Veldink, Jan H., additional, Hendrikse, Jeroen, additional, van den Heuvel, Martijn P., additional, and van den Berg, Leonard H., additional
- Published
- 2019
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41. Targeted genetic screen in amyotrophic lateral sclerosis reveals novel genetic variants with synergistic effect on clinical phenotype
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Cooper-Knock, Johnathan, Robins, Henry, Niedermoser, Isabell, Wyles, Matthew, Heath, Paul R., Higginbottom, Adrian, Walsh, Theresa, Kazoka, Mbombe, Al Kheifat, Ahmad, Al-Chalabi, Ammar, Basak, Nazli, Blair, Ian, Dekker, Annelot, Hardiman, Orla, Hide, Winston, Iacoangeli, Alfredo, Kenna, Kevin, Landers, John, McLaughlin, Russel, Mill, Jonathan, Middelkoop, Bas, Moisse, Mattieu, Pardina, Jesus Mora, Morrison, Karen, Newhouse, Stephen, Pulit, Sara, Shatunov, Aleksey, Shaw, Chris, Sproviero, William, Tazelaar, Gijs, van Damme, Philip, van den Berg, Leonard, van der Spek, Rick, Eijk, Kristelvan, van Es, Michael, van Rheenen, Wouter, van Vugt, Joke, Veldink, Jan, Kooyman, Maarten, Glass, Jonathan, Robberecht, Wim, Gotkine, Marc, Drory, Vivian, Kiernan, Matthew, Neto, Miguel Mitne, Ztaz, Mayana, Couratier, Philippe, Corcia, Philippe, Silani, Vincenzo, Chio, Adriano, and Project MinE ALS Sequencing Consortium
- Subjects
Oligogenic inheritance ,Cellular and Molecular Neuroscience ,C9ORF72 ,DNA sequencing ,RNA binding proteins ,Amyotrophic lateral sclerosis ,Molecular Biology - Abstract
Amyotrophic lateral sclerosis (ALS) is underpinned by an oligogenic rare variant architecture. Identified genetic variants of ALS include RNA-binding proteins containing prion-like domains (PrLDs). We hypothesized that screening genes encoding additional similar proteins will yield novel genetic causes of ALS. The most common genetic variant of ALS patients is a G4C2-repeat expansion within C9ORF72. We have shown that G4C2-repeat RNA sequesters RNA-binding proteins. A logical consequence of this is that loss-of-function mutations in G4C2-binding partners might contribute to ALS pathogenesis independently of and/or synergistically with C9ORF72 expansions. Targeted sequencing of genomic DNA encoding either RNA-binding proteins or known ALS genes (n = 274 genes) was performed in ALS patients to identify rare deleterious genetic variants and explore genotype-phenotype relationships. Genomic DNA was extracted from 103 ALS patients including 42 familial ALS patients and 61 young-onset (average age of onset 41 years) sporadic ALS patients; patients were chosen to maximize the probability of identifying genetic causes of ALS. Thirteen patients carried a G4C2-repeat expansion of C9ORF72. We identified 42 patients with rare deleterious variants; 6 patients carried more than one variant. Twelve mutations were discovered in known ALS genes which served as a validation of our strategy. Rare deleterious variants in RNA-binding proteins were significantly enriched in ALS patients compared to control frequencies (p = 5.31E-18). Nineteen patients featured at least one variant in a RNA-binding protein containing a PrLD. The number of variants per patient correlated with rate of disease progression (t-test, p = 0.033). We identified eighteen patients with a single variant in a G4C2-repeat binding protein. Patients with a G4C2-binding protein variant in combination with a C9ORF72 expansion had a significantly faster disease course (t-test, p = 0.025). Our data are consistent with an oligogenic model of ALS. We provide evidence for a number of entirely novel genetic variants of ALS caused by mutations in RNA-binding proteins. Moreover we show that these mutations act synergistically with each other and with C9ORF72 expansions to modify the clinical phenotype of ALS. A key finding is that this synergy is present only between functionally interacting variants. This work has significant implications for ALS therapy development.
- Published
- 2017
42. Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients
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DeYoung Joseph, Langfelder Peter, Fuller Tova F, Blauw Hylke M, van Es Michael A, van Vught Paul WJ, Horvath Steve, Saris Christiaan GJ, Wokke John HJ, Veldink Jan H, van den Berg Leonard H, and Ophoff Roel A
- Subjects
Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - 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.
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- 2009
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43. Detection of long repeat expansions from PCR-free whole-genome sequence data
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Dolzhenko, Egor, van Vugt, Joke J.F.A., Shaw, Richard J., Bekritsky, Mitchell A., van Blitterswijk, Marka, Narzisi, Giuseppe, Ajay, Subramanian S., Rajan, Vani, Kingsbury, Zoya, Humphray, Sean J., Schellevis, Raymond D., Brands, William J., Baker, Matt, Rademakers, Rosa, Kooyman, Maarten, Tazelaar, Gijs H.P., van Es, Michael A., McLaughlin, Russell, Sproviero, William, Shatunov, Aleksey, Jones, Ashley, Al Khleifat, Ahmad, Pittman, Alan, Morgan, Sarah, Hardiman, Orla, Al-Chalabi, Ammar, Shaw, Chris, Smith, Bradley, Neo, Edmund J., Morrison, Karen, Shaw, Pamela J., Reeves, Catherine, Winterkorn, Lara, Wexler, Nancy S., Housman, David E., Ng, Christopher, Li, Alina, Taft, Ryan J., van den Berg, Leonard H., Bentley, David R., Veldink, Jan H., and Eberle, Michael A.
- Subjects
Whole genome sequencing ,Genetics ,0303 health sciences ,03 medical and health sciences ,0302 clinical medicine ,Locus (genetics) ,Biology ,Trinucleotide repeat expansion ,Genome ,030217 neurology & neurosurgery ,030304 developmental biology ,3. Good health ,Southern blot - Abstract
Identifying large repeat expansions such as those that cause amyotrophic lateral sclerosis (ALS) and Fragile X syndrome is challenging for short-read (100-150 bp) whole genome sequencing (WGS) data. A solution to this problem is an important step towards integrating WGS into precision medicine. We have developed a software tool called ExpansionHunter that, using PCR-free WGS short-read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length. We applied our algorithm to WGS data from 3,001 ALS patients who have been tested for the presence of the C9orf72 repeat expansion with repeat-primed PCR (RP-PCR). Taking the RP-PCR calls as the ground truth, our WGS-based method identified pathogenic repeat expansions with 98.1% sensitivity and 99.7% specificity. Further inspection identified that all 11 conflicts were resolved as errors in the original RP-PCR results. Compared against this updated result, ExpansionHunter correctly classified all (212/212) of the expanded samples as either expansions (208) or potential expansions (4). Additionally, 99.9% (2,786/2,789) of the wild type samples were correctly classified as wild type by this method with the remaining two identified as possible expansions. We further applied our algorithm to a set of 144 samples where every sample had one of eight different pathogenic repeat expansions including examples associated with fragile X syndrome, Friedreich’s ataxia and Huntington’s disease and correctly flagged all of the known repeat expansions. Finally, we tested the accuracy of our method for short repeats by comparing our genotypes with results from 860 samples sized using fragment length analysis and determined that our calls were >95% accurate. ExpansionHunter can be used to accurately detect known pathogenic repeat expansions and provides researchers with a tool that can be used to identify new pathogenic repeat expansions.
- Published
- 2016
44. Derivation of norms for the Dutch version of the Edinburgh cognitive and behavioral ALS screen
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Bakker, Leonhard A., Schröder, Carin D., Spreij, Lauriane A., Verhaegen, Marianne, De Vocht, Joke, Van Damme, Philip, Veldink, Jan H., Visser-Meily, Johanna M.A., van den Berg, Leonard H., Nijboer, Tanja C.W., van Es, Michael A., Leerstoel Postma, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Afd Psychologische functieleer, Leerstoel Postma, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), and Afd Psychologische functieleer
- Subjects
Male ,Neurology ,Neuropsychological Tests ,Executive Function ,0302 clinical medicine ,Reference Values ,Amyotrophic lateral sclerosis ,Non-U.S. Gov't ,Language ,Netherlands ,SCORES ,Research Support, Non-U.S. Gov't ,Cognition ,ECAS ,IMPAIRMENT ,Middle Aged ,normative data ,Female ,Psychology ,Life Sciences & Biomedicine ,Clinical psychology ,medicine.medical_specialty ,Clinical Neurology ,Research Support ,DIAGNOSIS ,VALIDATION ,03 medical and health sciences ,AGE ,Memory ,cognitive dysfunction ,LATERAL-SCLEROSIS SCREEN ,medicine ,Journal Article ,Humans ,In patient ,Translations ,Aged ,Science & Technology ,medicine.disease ,DYSFUNCTION ,Clinical neurology ,VERBAL FLUENCY ,Case-Control Studies ,Normative ,Edinburgh cognitive and behavioral ALS screen ,Neurosciences & Neurology ,sense organs ,Neurology (clinical) ,030217 neurology & neurosurgery - Abstract
BACKGROUND: The Edinburgh cognitive and behavioral ALS screen (ECAS) was developed specifically to detect cognitive and behavioral changes in patients with amyotrophic lateral sclerosis (ALS). Differences with regard to normative data of different (language) versions of neuropsychological tests such as the ECAS exist. OBJECTIVE: To derive norms for the Dutch version of the ECAS. METHODS: Normative data were derived from a large sample of 690 control subjects and cognitive profiles were compared between a matched sample of 428 patients with ALS and 428 control subjects. RESULTS: Age, level of education, and sex were significantly associated with performance on the ECAS in the normative sample. ECAS data were not normally distributed and therefore normative data were expressed as percentile ranks. The comparison of ECAS scores between patients and control subjects demonstrated that patients obtained significantly lower scores for language, executive function, verbal fluency, and memory, which is in line with the established cognitive profile of ALS. CONCLUSION: For an accurate interpretation of ECAS results, it is important to derive normative data in large samples with nonparametric methods. The present normative data provide healthcare professionals with an accurate estimate of how common or uncommon patients' ECAS scores are and provide a useful supplement to existing cut-off scores. ispartof: AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION vol:20 issue:1-2 pages:19-27 ispartof: location:England status: published
- Published
- 2019
45. Whole blood transcriptome analysis in amyotrophic lateral sclerosis: A biomarker study
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van Rheenen, Wouter, primary, Diekstra, Frank P., additional, Harschnitz, Oliver, additional, Westeneng, Henk-Jan, additional, van Eijk, Kristel R., additional, Saris, Christiaan G. J., additional, Groen, Ewout J. N., additional, van Es, Michael A., additional, Blauw, Hylke M., additional, van Vught, Paul W. J., additional, Veldink, Jan H., additional, and van den Berg, Leonard H., additional
- Published
- 2018
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46. KIF1Avariants are a frequent cause of autosomal dominant hereditary spastic paraplegia
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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
- Abstract
Variants in the KIF1Agene can cause autosomal recessive spastic paraplegia 30, autosomal recessive hereditary sensory neuropathy, or autosomal (de novo) dominant mental retardation type 9. More recently, variants in KIF1Ahave also been described in a few cases with autosomal dominant spastic paraplegia. Here, we describe 20 KIF1Avariants in 24 patients from a clinical exome sequencing cohort of 347 individuals with a mostly ‘pure’ spastic paraplegia. In these patients, spastic paraplegia was slowly progressive and mostly pure, but with a highly variable disease onset (0–57 years). Segregation analyses showed a de novo occurrence in seven cases, and a dominant inheritance pattern in 11 families. The motor domain of KIF1A is a hotspot for disease causing variants in autosomal dominant spastic paraplegia, similar to mental retardation type 9 and recessive spastic paraplegia type 30. However, unlike these allelic disorders, dominant spastic paraplegia was also caused by loss-of-function variants outside this domain in six families. Finally, three missense variants were outside the motor domain and need further characterization. In conclusion, KIF1Avariants are a frequent cause of autosomal dominant spastic paraplegia in our cohort (6–7%). The identification of KIF1Aloss-of-function variants suggests haploinsufficiency as a possible mechanism in autosomal dominant spastic paraplegia.
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- 2020
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47. C9orf72 and UNC13A are shared risk loci for ALS and FTD: a genome-wide meta-analysis
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Diekstra, Frank P., Van Deerlin, Vivianna M., van Swieten, John C., Al-Chalabi, Ammar, Ludolph, Albert C., Weishaupt, Jochen H., Hardiman, Orla, Landers, John E., Brown, Robert H., van Es, Michael A., Pasterkamp, R. Jeroen, Koppers, Max, Andersen, Peter M., Estrada, Karol, Rivadeneira, Fernando, Hofman, Albert, Uitterlinden, André G., van Damme, Philip, Melki, Judith, Meininger, Vincent, Shatunov, Aleksey, Shaw, Christopher E., Leigh, P. Nigel, Shaw, Pamela J., Morrison, Karen E., Fogh, Isabella, Chiò, Adriano, Traynor, Bryan J., Czell, David, Weber, Markus, Heutink, Peter, de Bakker, Paul I. W., Silani, Vincenzo, Robberecht, Wim, van den Berg, Leonard H., and Veldink, Jan H.
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DNA Repeat Expansion ,C9orf72 Protein ,Frontotemporal Dementia ,Amyotrophic Lateral Sclerosis ,Mutation ,Humans ,Proteins ,Nerve Tissue Proteins ,Chromosomes, Human, Pair 9 ,Chromosomes, Human, Pair 19 ,Polymorphism, Single Nucleotide ,Article ,Genome-Wide Association Study - Abstract
Substantial clinical, pathological, and genetic overlap exists between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 inclusions have been found in both ALS and FTD cases (FTD-TDP). Recently, a repeat expansion in C9orf72 was identified as the causal variant in a proportion of ALS and FTD cases. We sought to identify additional evidence for a common genetic basis for the spectrum of ALS-FTD.We used published genome-wide association studies data for 4,377 ALS patients and 13,017 controls, and 435 pathology-proven FTD-TDP cases and 1,414 controls for genotype imputation. Data were analyzed in a joint meta-analysis, by replicating topmost associated hits of one disease in the other, and by using a conservative rank products analysis, allocating equal weight to ALS and FTD-TDP sample sizes.Meta-analysis identified 19 genome-wide significant single nucleotide polymorphisms (SNPs) in C9orf72 on chromosome 9p21.2 (lowest p = 2.6 × 10(-12) ) and 1 SNP in UNC13A on chromosome 19p13.11 (p = 1.0 × 10(-11) ) as shared susceptibility loci for ALS and FTD-TDP. Conditioning on the 9p21.2 genotype increased statistical significance at UNC13A. A third signal, on chromosome 8q24.13 at the SPG8 locus coding for strumpellin (p = 3.91 × 10(-7) ) was replicated in an independent cohort of 4,056 ALS patients and 3,958 controls (p = 0.026; combined analysis p = 1.01 × 10(-7) ).We identified common genetic variants in C9orf72, but in addition in UNC13A that are shared between ALS and FTD. UNC13A provides a novel link between ALS and FTD-TDP, and identifies changes in neurotransmitter release and synaptic function as a converging mechanism in the pathogenesis of ALS and FTD-TDP.
- Published
- 2014
48. Depolarized Inactivation Overcomes Impaired Activation to Produce DRG Neuron Hyperexcitability in a Nav1.7 Mutation in a Patient with Distal Limb Pain
- Author
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Huang, Jianying, primary, Yang, Yang, additional, Dib-Hajj, Sulayman D., additional, van Es, Michael, additional, Zhao, Peng, additional, Salomon, Jody, additional, Drenth, Joost P.H., additional, and Waxman, Stephen G., additional
- Published
- 2014
- Full Text
- View/download PDF
49. Genetic Overlap between Apparently Sporadic Motor Neuron Diseases
- Author
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van Blitterswijk, Marka, primary, Vlam, Lotte, additional, van Es, Michael A., additional, van der Pol, W-Ludo, additional, Hennekam, Eric A. M., additional, Dooijes, Dennis, additional, Schelhaas, Helenius J., additional, van der Kooi, Anneke J., additional, de Visser, Marianne, additional, Veldink, Jan H., additional, and van den Berg, Leonard H., additional
- Published
- 2012
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50. Detection of long repeat expansions from PCR-free whole-genome sequence data
- Author
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Dolzhenko, Egor, van Vugt, Joke J.F.A., Shaw, Richard J., Bekritsky, Mitchell A., van Blitterswijk, Marka, Narzisi, Giuseppe, Ajay, Subramanian S., Rajan, Vani, Lajoie, Bryan R., Johnson, Nathan H., Kingsbury, Zoya, Humphray, Sean J., Schellevis, Raymond D., Brands, William J., Baker, Matt, Rademakers, Rosa, Kooyman, Maarten, Tazelaar, Gijs H.P., van Es, Michael A., McLaughlin, Russell, Sproviero, William, Shatunov, Aleksey, Jones, Ashley, Al Khleifat, Ahmad, Pittman, Alan, Morgan, Sarah, Hardiman, Orla, Al-Chalabi, Ammar, Shaw, Chris, Smith, Bradley, Neo, Edmund J., Morrison, Karen, Shaw, Pamela J., Reeves, Catherine, Winterkorn, Lara, Wexler, Nancy S., Housman, David E., Ng, Christopher W., Li, Alina L., Taft, Ryan J., van den Berg, Leonard H., Bentley, David R., Veldink, Jan H., and Eberle, Michael A.
- Abstract
Identifying large expansions of short tandem repeats (STRs), such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome, is challenging for short-read whole-genome sequencing (WGS) data. A solution to this problem is an important step toward integrating WGS into precision medicine. We developed a software tool called ExpansionHunter that, using PCR-free WGS short-read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length. We applied our algorithm to WGS data from 3001 ALS patients who have been tested for the presence of the C9orf72repeat expansion with repeat-primed PCR (RP-PCR). Compared against this truth data, ExpansionHunter correctly classified all (212/212, 95% CI [0.98, 1.00]) of the expanded samples as either expansions (208) or potential expansions (4). Additionally, 99.9% (2786/2789, 95% CI [0.997, 1.00]) of the wild-type samples were correctly classified as wild type by this method with the remaining three samples identified as possible expansions. We further applied our algorithm to a set of 152 samples in which every sample had one of eight different pathogenic repeat expansions, including those associated with fragile X syndrome, Friedreich's ataxia, and Huntington's disease, and correctly flagged all but one of the known repeat expansions. Thus, ExpansionHunter can be used to accurately detect known pathogenic repeat expansions and provides researchers with a tool that can be used to identify new pathogenic repeat expansions.
- Published
- 2017
- Full Text
- View/download PDF
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