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1. Dominant mutations of the Notch ligand Jagged1 cause peripheral neuropathy

Author: Sullivan, Jeremy M., Motley, William W., Johnson, Janel O., Aisenberg, William H., Marshall, Katherine L., Barwick, Katy E.S., Kong, Lingling, Huh, Jennifer S., Saavedra-Rivera, Pamela C., McEntagart, Meriel M., Marion, Marie- Helene, Hicklin, Lucy A., Modarres, Hamid, Baple, Emma L., Farah, Mohamed H., Zuberi, Aamir R., Lutz, Cathleen M., Gaudet, Rachelle, Traynor, Bryan J., Crosby, Andrew H., and Sumner, Charlotte J.
Subjects: Therapeutics -- Health aspects, Post-translational modifications, Paralysis, Medical schools, Charcot-Marie-Tooth disease, Toxicity, Homeostasis, Diseases, Health care industry
Abstract: Notch signaling is a highly conserved intercellular pathway with tightly regulated and pleiotropic roles in normal tissue development and homeostasis. Dysregulated Notch signaling has also been implicated in human disease, including multiple forms of cancer, and represents an emerging therapeutic target. Successful development of such therapeutics requires a detailed understanding of potential on-target toxicities. Here, we identify autosomal dominant mutations of the canonical Notch ligand Jagged1 (or JAG1) as a cause of peripheral nerve disease in 2 unrelated families with the hereditary axonal neuropathy Charcot-Marie-Tooth disease type 2 (CMT2). Affected individuals in both families exhibited severe vocal fold paresis, a rare feature of peripheral nerve disease that can be life- threatening. Our studies of mutant protein posttranslational modification and localization indicated that the mutations (p.Ser577Arg, p.Ser650Pro) impair protein glycosylation and reduce JAG1 cell surface expression. Mice harboring heterozygous CMT2-associated mutations exhibited mild peripheral neuropathy, and homozygous expression resulted in embryonic lethality by midgestation. Together, our findings highlight a critical role for JAG1 in maintaining peripheral nerve integrity, particularly in the recurrent laryngeal nerve, and provide a basis for the evaluation of peripheral neuropathy as part of the clinical development of Notch pathway-modulating therapeutics., Introduction The Notch pathway is a highly conserved cell-cell signaling mechanism that functions in virtually all tissues to regulate multiple aspects of cell fate and homeostasis. Dysregulation of Notch signaling [...]
Published: 2020
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2. A Genome-Wide Association Study of Myasthenia Gravis

Author: Renton, Alan E, Pliner, Hannah A, Provenzano, Carlo, Evoli, Amelia, Ricciardi, Roberta, Nalls, Michael A, Marangi, Giuseppe, Abramzon, Yevgeniya, Arepalli, Sampath, Chong, Sean, Hernandez, Dena G, Johnson, Janel O, Bartoccioni, Emanuela, Scuderi, Flavia, Maestri, Michelangelo, Gibbs, J Raphael, Errichiello, Edoardo, Chiò, Adriano, Restagno, Gabriella, Sabatelli, Mario, Macek, Mark, Scholz, Sonja W, Corse, Andrea, Chaudhry, Vinay, Benatar, Michael, Barohn, Richard J, McVey, April, Pasnoor, Mamatha, Dimachkie, Mazen M, Rowin, Julie, Kissel, John, Freimer, Miriam, Kaminski, Henry J, Sanders, Donald B, Lipscomb, Bernadette, Massey, Janice M, Chopra, Manisha, Howard, James F, Koopman, Wilma J, Nicolle, Michael W, Pascuzzi, Robert M, Pestronk, Alan, Wulf, Charlie, Florence, Julaine, Blackmore, Derrick, Soloway, Aimee, Siddiqi, Zaeem, Muppidi, Srikanth, Wolfe, Gil, Richman, David, Mezei, Michelle M, Jiwa, Theresa, Oger, Joel, Drachman, Daniel B, and Traynor, Bryan J
Subjects: Rare Diseases, Genetics, Neurosciences, Autoimmune Disease, Myasthenia Gravis, Clinical Research, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Adult, Age of Onset, CTLA-4 Antigen, Case-Control Studies, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, HLA-DQ alpha-Chains, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, United States, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract: ImportanceMyasthenia gravis is a chronic, autoimmune, neuromuscular disease characterized by fluctuating weakness of voluntary muscle groups. Although genetic factors are known to play a role in this neuroimmunological condition, the genetic etiology underlying myasthenia gravis is not well understood.ObjectiveTo identify genetic variants that alter susceptibility to myasthenia gravis, we performed a genome-wide association study.Design, setting, and participantsDNA was obtained from 1032 white individuals from North America diagnosed as having acetylcholine receptor antibody-positive myasthenia gravis and 1998 race/ethnicity-matched control individuals from January 2010 to January 2011. These samples were genotyped on Illumina OmniExpress single-nucleotide polymorphism arrays. An independent cohort of 423 Italian cases and 467 Italian control individuals were used for replication.Main outcomes and measuresWe calculated P values for association between 8,114,394 genotyped and imputed variants across the genome and risk for developing myasthenia gravis using logistic regression modeling. A threshold P value of 5.0×10(-8) was set for genome-wide significance after Bonferroni correction for multiple testing.ResultsIn the overall case-control cohort, we identified association signals at CTLA4 (rs231770; P=3.98×10(-8); odds ratio, 1.37; 95% CI, 1.25-1.49), HLA-DQA1 (rs9271871; P=1.08×10(-8); odds ratio, 2.31; 95% CI, 2.02-2.60), and TNFRSF11A (rs4263037; P=1.60×10(-9); odds ratio, 1.41; 95% CI, 1.29-1.53). These findings replicated for CTLA4 and HLA-DQA1 in an independent cohort of Italian cases and control individuals. Further analysis revealed distinct, but overlapping, disease-associated loci for early- and late-onset forms of myasthenia gravis. In the late-onset cases, we identified 2 association peaks: one was located in TNFRSF11A (rs4263037; P=1.32×10(-12); odds ratio, 1.56; 95% CI, 1.44-1.68) and the other was detected in the major histocompatibility complex on chromosome 6p21 (HLA-DQA1; rs9271871; P=7.02×10(-18); odds ratio, 4.27; 95% CI, 3.92-4.62). Association within the major histocompatibility complex region was also observed in early-onset cases (HLA-DQA1; rs601006; P=2.52×10(-11); odds ratio, 4.0; 95% CI, 3.57-4.43), although the set of single-nucleotide polymorphisms was different from that implicated among late-onset cases.Conclusions and relevanceOur genetic data provide insights into aberrant cellular mechanisms responsible for this prototypical autoimmune disorder. They also suggest that clinical trials of immunomodulatory drugs related to CTLA4 and that are already Food and Drug Administration approved as therapies for other autoimmune diseases could be considered for patients with refractory disease.
Published: 2015

3. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

Author: Logullo, Francesco O., Simone, Isabella, Logroscino, Giancarlo, Salvi, Fabrizio, Bartolomei, Ilaria, Borghero, Giuseppe, Murru, Maria Rita, Costantino, Emanuela, Pani, Carla, Puddu, Roberta, Caredda, Carla, Piras, Valeria, Tranquilli, Stefania, Cuccu, Stefania, Corongiu, Daniela, Melis, Maurizio, Milia, Antonio, Marrosu, Francesco, Marrosu, Maria Giovanna, Floris, Gianluca, Cannas, Antonino, Capasso, Margherita, Caponnetto, Claudia, Mancardi, Gianluigi, Origone, Paola, Mandich, Paola, Conforti, Francesca L., Cavallaro, Sebastiano, Mora, Gabriele, Marinou, Kalliopi, Sideri, Riccardo, Penco, Silvana, Mosca, Lorena, Lunetta, Christian, Pinter, Giuseppe Lauria, Corbo, Massimo, Riva, Nilo, Carrera, Paola, Volanti, Paolo, Mandrioli, Jessica, Fini, Nicola, Fasano, Antonio, Tremolizzo, Lucio, Arosio, Alessandro, Ferrarese, Carlo, Trojsi, Francesca, Tedeschi, Gioacchino, Monsurrò, Maria Rosaria, Piccirillo, Giovanni, Femiano, Cinzia, Ticca, Anna, Ortu, Enzo, La Bella, Vincenzo, Spataro, Rossella, Colletti, Tiziana, Sabatelli, Mario, Zollino, Marcella, Conte, Amelia, Luigetti, Marco, Lattante, Serena, Marangi, Giuseppe, Santarelli, Marialuisa, Petrucci, Antonio, Pugliatti, Maura, Pirisi, Angelo, Parish, Leslie D., Occhineri, Patrizia, Giannini, Fabio, Battistini, Stefania, Ricci, Claudia, Benigni, Michele, Cau, Tea B., Loi, Daniela, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Barberis, Marco, Restagno, Gabriella, Casale, Federico, Marrali, Giuseppe, Fuda, Giuseppe, Ossola, Irene, Cammarosano, Stefania, Canosa, Antonio, Ilardi, Antonio, Manera, Umberto, Grassano, Maurizio, Tanel, Raffaella, Pisano, Fabrizio, Harms, Matthew B., Goldstein, David B., Shneider, Neil A., Goutman, Stephen, Simmons, Zachary, Miller, Timothy M., Chandran, Siddharthan, Pal, Suvankar, Manousakis, Georgios, Appel, Stanley H., Simpson, Ericka, Wang, Leo, Baloh, Robert H., Gibson, Summer, Bedlack, Richard, Lacomis, David, Sareen, Dhruv, Sherman, Alexander, Bruijn, Lucie, Penny, Michelle, Allen, Andrew S., Appel, Stanley, Bedlack, Richard S., Boone, Braden E., Brown, Robert, Carulli, John P., Chesi, Alessandra, Chung, Wendy K., Cirulli, Elizabeth T., Cooper, Gregory M., Couthouis, Julien, Day-Williams, Aaron G., Dion, Patrick A., Gitler, Aaron D., Glass, Jonathan D., Han, Yujun, Harris, Tim, Hayes, Sebastian D., Jones, Angela L., Keebler, Jonathan, Krueger, Brian J., Lasseigne, Brittany N., Levy, Shawn E., Lu, Yi-Fan, Maniatis, Tom, McKenna-Yasek, Diane, Myers, Richard M., Petrovski, Slavé, Pulst, Stefan M., Raphael, Alya R., Ravits, John M., Ren, Zhong, Rouleau, Guy A., Sapp, Peter C., Sims, Katherine B., Staropoli, John F., Waite, Lindsay L., Wang, Quanli, Wimbish, Jack R., Xin, Winnie W., Phatnani, Hemali, Kwan, Justin, Broach, James R., Arcila-Londono, Ximena, Lee, Edward B., Van Deerlin, Vivianna M., Fraenkel, Ernest, Ostrow, Lyle W., Baas, Frank, Zaitlen, Noah, Berry, James D., Malaspina, Andrea, Fratta, Pietro, Cox, Gregory A., Thompson, Leslie M., Finkbeiner, Steve, Dardiotis, Efthimios, Hornstein, Eran, MacGowan, Daniel J., Heiman-Patterson, Terry, Hammell, Molly G., Patsopoulos, Nikolaos A., Dubnau, Joshua, Nath, Avindra, Kaye, Julia, Finkbeiner, Steven, Wyman, Stacia, LeNail, Alexander, Lima, Leandro, Rothstein, Jeffrey D., Svendsen, Clive N., Van Eyk, Jenny, Maragakis, Nicholas J., Kolb, Stephen J., Cudkowicz, Merit, Baxi, Emily, Benatar, Michael, Taylor, J. Paul, Wu, Gang, Rampersaud, Evadnie, Wuu, Joanne, Rademakers, Rosa, Züchner, Stephan, Schule, Rebecca, McCauley, Jacob, Hussain, Sumaira, Cooley, Anne, Wallace, Marielle, Clayman, Christine, Barohn, Richard, Statland, Jeffrey, Ravits, John, Swenson, Andrea, Jackson, Carlayne, Trivedi, Jaya, Khan, Shaida, Katz, Jonathan, Jenkins, Liberty, Burns, Ted, Gwathmey, Kelly, Caress, James, McMillan, Corey, Elman, Lauren, Pioro, Erik, Heckmann, Jeannine, So, Yuen, Walk, David, Maiser, Samuel, Zhang, Jinghui, Silani, Vincenzo, Ticozzi, Nicola, Gellera, Cinzia, Ratti, Antonia, Taroni, Franco, Lauria, Giuseppe, Verde, Federico, Fogh, Isabella, Tiloca, Cinzia, Comi, Giacomo P., Sorarù, Gianni, Cereda, Cristina, D’Alfonso, Sandra, Corrado, Lucia, De Marchi, Fabiola, Corti, Stefania, Ceroni, Mauro, Mazzini, Letizia, Siciliano, Gabriele, Filosto, Massimiliano, Inghilleri, Maurizio, Peverelli, Silvia, Colombrita, Claudia, Poletti, Barbara, Maderna, Luca, Del Bo, Roberto, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, Pensato, Viviana, Castellotti, Barbara, Camu, William, Mouzat, Kevin, Lumbroso, Serge, Corcia, Philippe, Meininger, Vincent, Besson, Gérard, Lagrange, Emmeline, Clavelou, Pierre, Guy, Nathalie, Couratier, Philippe, Vourch, Patrick, Danel, Véronique, Bernard, Emilien, Lemasson, Gwendal, Al Kheifat, Ahmad, Al-Chalabi, Ammar, Andersen, Peter, Basak, A. Nazli, Blair, Ian P., Chio, Adriano, Cooper-Knock, Jonathan, de Carvalho, Mamede, Dekker, Annelot, Drory, Vivian, Redondo, Alberto Garcia, Gotkine, Marc, Hardiman, Orla, Hide, Winston, Iacoangeli, Alfredo, Glass, Jonathan, Kenna, Kevin, Kiernan, Matthew, Kooyman, Maarten, Landers, John, McLaughlin, Russell, Middelkoop, Bas, Mill, Jonathan, Neto, Miguel Mitne, Moisse, Mattieu, Pardina, Jesus Mora, Morrison, Karen, Newhouse, Stephen, Pinto, Susana, Pulit, Sara, Robberecht, Wim, Shatunov, Aleksey, Shaw, Pamela, Shaw, Chris, Sproviero, William, Tazelaar, Gijs, van Damme, Philip, van den Berg, Leonard, van der Spek, Rick, van Eijk, Kristel, van Es, Michael, van Rheenen, Wouter, van Vugt, Joke, Veldink, Jan, Weber, Markus, Williams, Kelly L., Zatz, Mayana, Bauer, Denis C., Twine, Natalie A., Nicolas, Aude, Kenna, Kevin P., Renton, Alan E., Faghri, Faraz, Chia, Ruth, Dominov, Janice A., Kenna, Brendan J., Nalls, Mike A., Keagle, Pamela, Rivera, Alberto M., Murphy, Natalie A., van Vugt, Joke J.F.A., Geiger, Joshua T., Van der Spek, Rick A., Pliner, Hannah A., Shankaracharya, Smith, Bradley N., Topp, Simon D., Abramzon, Yevgeniya, Gkazi, Athina Soragia, Eicher, John D., Kenna, Aoife, Messina, Sonia, Simone, Isabella L., Ferrucci, Luigi, Moreno, Cristiane de Araujo Martins, Kamalakaran, Sitharthan, Musunuri, Rajeeva Lochan, Evani, Uday Shankar, Abhyankar, Avinash, Zody, Michael C., Wyman, Stacia K., LeNail, Alex, Van Eyk, Jennifer E., Laaksovirta, Hannu, Myllykangas, Liisa, Jansson, Lilja, Valori, Miko, Ealing, John, Hamdalla, Hisham, Rollinson, Sara, Pickering-Brown, Stuart, Orrell, Richard W., Sidle, Katie C., Hardy, John, Singleton, Andrew B., Johnson, Janel O., Arepalli, Sampath, Polak, Meraida, Asress, Seneshaw, Al-Sarraj, Safa, King, Andrew, Troakes, Claire, Vance, Caroline, de Belleroche, Jacqueline, ten Asbroek, Anneloor L.M.A., Muñoz-Blanco, José Luis, Hernandez, Dena G., Ding, Jinhui, Gibbs, J. Raphael, Scholz, Sonja W., Floeter, Mary Kay, Campbell, Roy H., Landi, Francesco, Bowser, Robert, MacGowan, Daniel J.L., Kirby, Janine, Pioro, Erik P., Pamphlett, Roger, Broach, James, Gerhard, Glenn, Dunckley, Travis L., Brady, Christopher B., Kowall, Neil W., Troncoso, Juan C., Le Ber, Isabelle, Heiman-Patterson, Terry D., Kamel, Freya, Van Den Bosch, Ludo, Strom, Tim M., Meitinger, Thomas, Van Eijk, Kristel R., Moisse, Matthieu, McLaughlin, Russell L., Van Es, Michael A., Boylan, Kevin B., Van Blitterswijk, Marka, Morrison, Karen E., Mora, Jesús S., Drory, Vivian E., Shaw, Pamela J., Turner, Martin R., Talbot, Kevin, Fifita, Jennifer A., Nicholson, Garth A., Esteban-Pérez, Jesús, García-Redondo, Alberto, Rogaeva, Ekaterina, Zinman, Lorne, Cooper-Knock, Johnathan, Brice, Alexis, Goutman, Stephen A., Feldman, Eva L., Gibson, Summer B., Van Damme, Philip, Ludolph, Albert C., Andersen, Peter M., Weishaupt, Jochen H., Trojanowski, John Q., Brown, Robert H., Jr., van den Berg, Leonard H., Veldink, Jan H., Stone, David J., Tienari, Pentti, Chiò, Adriano, Shaw, Christopher E., Traynor, Bryan J., and Landers, John E.
Published: 2018
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4. Hereditary Spastic Paraplegia Type 43 (SPG43) is Caused by Mutation in C19orf12

Author: Landouré, Guida, Zhu, Peng‐Peng, Lourenço, Charles M, Johnson, Janel O, Toro, Camilo, Bricceno, Katherine V, Rinaldi, Carlo, Meilleur, Katherine G, Sangaré, Modibo, Diallo, Oumarou, Pierson, Tyler M, Ishiura, Hiroyuki, Tsuji, Shoji, Hein, Nichole, Fink, John K, Stoll, Marion, Nicholson, Garth, Gonzalez, Michael A, Speziani, Fiorella, Dürr, Alexandra, Stevanin, Giovanni, Biesecker, Leslie G, Center, for the NIH Intramural Sequencing, Accardi, John, Landis, Dennis MD, Gahl, William A, Traynor, Bryan J, Marques, Wilson, Züchner, Stephan, Blackstone, Craig, Fischbeck, Kenneth H, and Burnett, Barrington G
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Genetics, Rare Diseases, Neurosciences, Human Genome, Clinical Research, Neurodegenerative, Aetiology, 2.1 Biological and endogenous factors, Adolescent, Amino Acid Sequence, Brain, Homozygote, Humans, Intracellular Space, Magnetic Resonance Imaging, Male, Mitochondrial Proteins, Molecular Sequence Data, Mutation, Protein Transport, Sequence Alignment, Sequence Deletion, Spastic Paraplegia, Hereditary, SPG43, NBIA, C19orf12, hereditary spastic paraplegia, NIH Intramural Sequencing Center, Clinical Sciences, Genetics & Heredity, Clinical sciences
Abstract: We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three-nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain.
Published: 2013

5. Exome sequencing establishes a gelsolin mutation as the cause of inherited bulbar‐onset neuropathy

Author: Caress, James B., Johnson, Janel O., Abramzon, Yevgeniya A., Hawkins, Gregory A., Gibbs, J. Raphael, Sullivan, Elizabeth A., Chahal, Chamanpreet S., and Traynor, Bryan J.
Published: 2017
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6. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study

Author: Majounie, Elisa, Renton, Alan E, Mok, Kin, Dopper, Elise GP, Waite, Adrian, Rollinson, Sara, Chiò, Adriano, Restagno, Gabriella, Nicolaou, Nayia, Simon-Sanchez, Javier, van Swieten, John C, Abramzon, Yevgeniya, Johnson, Janel O, Sendtner, Michael, Pamphlett, Roger, Orrell, Richard W, Mead, Simon, Sidle, Katie C, Houlden, Henry, Rohrer, Jonathan D, Morrison, Karen E, Pall, Hardev, Talbot, Kevin, Ansorge, Olaf, Hernandez, Dena G, Arepalli, Sampath, Sabatelli, Mario, Mora, Gabriele, Corbo, Massimo, Giannini, Fabio, Calvo, Andrea, Englund, Elisabet, Borghero, Giuseppe, Floris, Gian Luca, Remes, Anne M, Laaksovirta, Hannu, McCluskey, Leo, Trojanowski, John Q, Van Deerlin, Vivianna M, Schellenberg, Gerard D, Nalls, Michael A, Drory, Vivian E, Lu, Chin-Song, Yeh, Tu-Hsueh, Ishiura, Hiroyuki, Takahashi, Yuji, Tsuji, Shoji, Le Ber, Isabelle, Brice, Alexis, Drepper, Carsten, Williams, Nigel, Kirby, Janine, Shaw, Pamela, Hardy, John, Tienari, Pentti J, Heutink, Peter, Morris, Huw R, Pickering-Brown, Stuart, and Traynor, Bryan J
Published: 2012
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7. Kinesin-associated protein 3 (KIFAP3) has no effect on survival in a population-based cohort of ALS patients

Author: Traynor, Bryan J., Nalls, Michael, Lai, Shiao-Lin, Gibbs, Raphael J., Schymick, Jennifer C., Arepalli, Sampath, Hernandez, Dena, van der Brug, Marcel P., Johnson, Janel O., Dillman, Allissa, Cookson, Mark, Moglia, Cristina, Calvo, Andrea, Restagno, Gabriella, Mora, Gabriele, Chiò, Adriano, and Cleveland, Don W.
Published: 2010

8. Variants in ATP6V0A1 cause progressive myoclonus epilepsy and developmental and epileptic encephalopathy

Author: Bott, Laura C, Forouhan, Mitra, Lieto, Maria, Sala, Ambre J, Ellerington, Ruth, Johnson, Janel O, Speciale, Alfina A, Criscuolo, Chiara, Filla, Alessandro, Chitayat, David, Alkhunaizi, Ebba, Shannon, Patrick, Nemeth, Andrea H, Angelucci, Francesco, Lim, Wooi Fang, Striano, Pasquale, Zara, Federico, Helbig, Ingo, Muona, Mikko, Courage, Carolina, Lehesjoki, Anna-Elina, Berkovic, Samuel F, Fischbeck, Kenneth H, Brancati, Francesco, Morimoto, Richard I, Wood, Matthew J A, Rinaldi, Carlo, Research Programs Unit, Medicum, University of Helsinki, Department of Medical and Clinical Genetics, and HUSLAB
Subjects: EXPRESSION, Caenorhabditis elegans disease modelling, CUTIS LAXA, MUTATIONS, lysosomal disease, 3112 Neurosciences, General Engineering, V-ATPASE, 3124 Neurology and psychiatry, epileptic encephalopathy, V-ATPase, organelle acidification, VACUOLAR PROTON PUMP, SUBUNIT, RENAL TUBULAR-ACIDOSIS, H+-ATPASE, CAENORHABDITIS-ELEGANS, CATHEPSIN-D DEFICIENCY
Abstract: Bott et al. here reports that de novo and biallelic variants in ATP6V0A1 gene affect the ability of the V-ATPase complex to translocate protons and acidify the endolysosomal compartment in neurons, causing a severe neurological phenotype ranging from developmental and epileptic encephalopathy to progressive myoclonus epilepsy. The vacuolar H+-ATPase is a large multi-subunit proton pump, composed of an integral membrane V0 domain, involved in proton translocation, and a peripheral V1 domain, catalysing ATP hydrolysis. This complex is widely distributed on the membrane of various subcellular organelles, such as endosomes and lysosomes, and plays a critical role in cellular processes ranging from autophagy to protein trafficking and endocytosis. Variants in ATP6V0A1, the brain-enriched isoform in the V0 domain, have been recently associated with developmental delay and epilepsy in four individuals. Here, we identified 17 individuals from 14 unrelated families with both with new and previously characterized variants in this gene, representing the largest cohort to date. Five affected subjects with biallelic variants in this gene presented with a phenotype of early-onset progressive myoclonus epilepsy with ataxia, while 12 individuals carried de novo missense variants and showed severe developmental and epileptic encephalopathy. The R740Q mutation, which alone accounts for almost 50% of the mutations identified among our cases, leads to failure of lysosomal hydrolysis by directly impairing acidification of the endolysosomal compartment, causing autophagic dysfunction and severe developmental defect in Caenorhabditis elegans. Altogether, our findings further expand the neurological phenotype associated with variants in this gene and provide a direct link with endolysosomal acidification in the pathophysiology of ATP6V0A1-related conditions.
Published: 2021

9. Association of a Novel ACTA1 Mutation With a Dominant Progressive Scapuloperoneal Myopathy in an Extended Family

Author: Zukosky, Kristen, Meilleur, Katherine, Traynor, Bryan J., Dastgir, Jahannaz, Medne, Livija, Devoto, Marcella, Collins, James, Rooney, Jachinta, Zou, Yaqun, Yang, Michele L., Gibbs, J. Raphael, Meier, Markus, Stetefeld, Joerg, Finkel, Richard S., Schessl, Joachim, Elman, Lauren, Felice, Kevin, Ferguson, Toby A., Ceyhan-Birsoy, Ozge, Beggs, Alan H., Tennekoon, Gihan, Johnson, Janel O., and Bönnemann, Carsten G.
Published: 2015
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10. Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia

Author: Rinaldi, Carlo, Schmidt, Thomas, Situ, Alan J., Johnson, Janel O., Lee, Philip R., Chen, Ke-lian, Bott, Laura C., Fadó, Rut, Harmison, George H., Parodi, Sara, Grunseich, Christopher, Renvoisé, Benoît, Biesecker, Leslie G., De Michele, Giuseppe, Santorelli, Filippo M., Filla, Alessandro, Stevanin, Giovanni, Dürr, Alexandra, Brice, Alexis, Casals, Núria, Traynor, Bryan J., Blackstone, Craig, Ulmer, Tobias S., and Fischbeck, Kenneth H.
Published: 2015
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11. A 7.5-Mb Duplication at Chromosome 11Q21–11Q22.3 Is Associated With A Novel Spastic Ataxia Syndrome

Author: Johnson, Janel O., Stevanin, Giovanni, van de Leemput, Joyce, Hernandez, Dena G., Arepalli, Sampath, Forlani, Sylvie, Zonozi, Reza, Gibbs, Raphael J., Brice, Alexis, Durr, Alexandra, and Singleton, Andrew B.
Published: 2015
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12. ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion

Author: Chiò, Adriano, Mora, Gabriele, Sabatelli, Mario, Caponnetto, Claudia, Lunetta, Christian, Traynor, Bryan J., Johnson, Janel O., Nalls, Mike A., Calvo, Andrea, Moglia, Cristina, Borghero, Giuseppe, Trojsi, Francesca, La Bella, Vincenzo, Volanti, Paolo, Simone, Isabella, Salvi, Fabrizio, Logullo, Francesco O., Riva, Nilo, Carrera, Paola, Giannini, Fabio, Mandrioli, Jessica, Tanel, Raffaella, Capasso, Margherita, Tremolizzo, Lucio, Battistini, Stefania, Murru, Maria Rita, Origone, Paola, Zollino, Marcella, Penco, Silvana, Mazzini, Letizia, D'Alfonso, Sandra, Restagno, Gabriella, Brunetti, Maura, Barberis, Marco, and Conforti, Francesca L.
Published: 2016
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13. Mutations in the CHCHD10 gene are a common cause of familial amyotrophic lateral sclerosis

Author: Johnson, Janel O., Glynn, Shannon M., Gibbs, J. Raphael, Nalls, Mike A., Sabatelli, Mario, Restagno, Gabriella, Drory, Vivian E., Chiò, Adriano, Rogaeva, Ekaterina, and Traynor, Bryan J.
Published: 2014
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14. Association of variants in the SPTLC1 gene with juvenile amyotrophic lateral sclerosis

Author: Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512); Palvadeau, Robin, Johnson, Janel O.; Chia, Ruth; Miller, Danny E.; Li, Rachel; Kumaran, Ravindran; Abramzon, Yevgeniya; Alahmady, Nada; Renton, Alan E.; Topp, Simon D.; Gibbs, J. Raphael; Cookson, Mark R.; Sabir, Marya S.; Dalgard, Clifton L.; Troakes, Claire; Jones, Ashley R.; Shatunov, Aleksey; Lacoangeli, Alfredo; Al Khleifat, Ahmad; Ticozzi, Nicola; Silani, Vincenzo; Gellera, Cinzia; Blair, Ian P.; Dobson-Stone, Carol; Kwok, John B.; Bonkowski, Emily S.; Palvadeau, Robin; Tienari, Pentti J.; Morrison, Karen E.; Shaw, Pamela J.; Al-Chalabi, Ammar; Jr, Robert H. Brown; Calvo, Andrea; Mora, Gabriele; Al-Saif, Hind; Gotkine, Marc; Leigh, Fawn; Chang, Irene J.; Perlman, Seth J.; Glass, Ian; Scott, Anna, I.; Landers, John E.; Chio, Adriano; Crawford, Thomas O.; Smith, Bradley N.; Traynor, Bryan J., Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512); Palvadeau, Robin, and Johnson, Janel O.; Chia, Ruth; Miller, Danny E.; Li, Rachel; Kumaran, Ravindran; Abramzon, Yevgeniya; Alahmady, Nada; Renton, Alan E.; Topp, Simon D.; Gibbs, J. Raphael; Cookson, Mark R.; Sabir, Marya S.; Dalgard, Clifton L.; Troakes, Claire; Jones, Ashley R.; Shatunov, Aleksey; Lacoangeli, Alfredo; Al Khleifat, Ahmad; Ticozzi, Nicola; Silani, Vincenzo; Gellera, Cinzia; Blair, Ian P.; Dobson-Stone, Carol; Kwok, John B.; Bonkowski, Emily S.; Palvadeau, Robin; Tienari, Pentti J.; Morrison, Karen E.; Shaw, Pamela J.; Al-Chalabi, Ammar; Jr, Robert H. Brown; Calvo, Andrea; Mora, Gabriele; Al-Saif, Hind; Gotkine, Marc; Leigh, Fawn; Chang, Irene J.; Perlman, Seth J.; Glass, Ian; Scott, Anna, I.; Landers, John E.; Chio, Adriano; Crawford, Thomas O.; Smith, Bradley N.; Traynor, Bryan J.
Abstract: Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective: to identify the genetic variants associated with juvenile ALS. Design, setting, and participants: in this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main outcomes and measures: De novo variants present only in the index case and not in unaffected family members. Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p. Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesi
Published: 2021

15. Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Author: Johnson, J, Chia, R, Miller, D, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, A, Topp, S, Gibbs, J, Cookson, M, Sabir, M, Dalgard, C, Troakes, C, Jones, A, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, I, Dobson-Stone, C, Kwok, J, Bonkowski, E, Palvadeau, R, Tienari, P, Morrison, K, Shaw, P, Al-Chalabi, A, Brown, R, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, I, Perlman, S, Glass, I, Scott, A, Shaw, C, Basak, A, Landers, J, Chiò, A, Crawford, T, Smith, B, Traynor, B, Fallini, C, Gkazi, A, Scotter, E, Kenna, K, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, Ten Asbroek, A, McKenna-Yasek, D, Mclaughlin, R, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D'Alfonso, S, Mazzini, L, Comi, G, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, K, Nicholson, G, Leblond-Manry, C, Rouleau, G, Hardiman, O, Veldink, J, van den Berg, L, Pall, H, Turner, M, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, J, Ratti, A, Adeleye, A, Soltis, A, Alba, C, Viollet, C, Bacikova, D, Hupalo, D, Sukumar, G, Pollard, H, Wilkerson, M, Martinez, E, Ahmed, S, Arepalli, S, Baloh, R, Bowser, R, Brady, C, Brice, A, Broach, J, Campbell, R, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, V, Dunckley, T, Eicher, J, England, B, Faghri, F, Feldman, E, Floeter, M, Fratta, P, Geiger, J, Gerhard, G, Gibson, S, Hardy, J, Harms, M, Heiman-Patterson, T, Hernandez, D, Jansson, L, Kirby, J, Kowall, N, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, Macgowan, D, Maragakis, N, Mouzat, K, Murphy, N, Myllykangas, L, Nalls, M, Orrell, R, Ostrow, L, Pamphlett, R, Pickering-Brown, S, Pioro, E, Pletnikova, O, Pliner, H, Pulst, S, Ravits, J, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, J, Scholz, S, Sendtner, M, Sidle, K, Simmons, Z, Singleton, A, Smith, N, Stone, D, Troncoso, J, Valori, M, Van Damme, P, Van Deerlin, V, Van Den Bosch, L, Zinman, L, Angelocola, S, Ausiello, F, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, T, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, F, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D'Errico, E, Demarco, G, Dubbioso, R, Ferrarese, C, Ferraro, P, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, F, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, M, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, M, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, Johnson, Janel O, Chia, Ruth, Miller, Danny E, Li, Rachel, Kumaran, Ravindran, Abramzon, Yevgeniya, Alahmady, Nada, Renton, Alan E, Topp, Simon D, Gibbs, J Raphael, Cookson, Mark R, Sabir, Marya S, Dalgard, Clifton L, Troakes, Claire, Jones, Ashley R, Shatunov, Aleksey, Iacoangeli, Alfredo, Al Khleifat, Ahmad, Ticozzi, Nicola, Silani, Vincenzo, Gellera, Cinzia, Blair, Ian P, Dobson-Stone, Carol, Kwok, John B, Bonkowski, Emily S, Palvadeau, Robin, Tienari, Pentti J, Morrison, Karen E, Shaw, Pamela J, Al-Chalabi, Ammar, Brown, Robert H, Calvo, Andrea, Mora, Gabriele, Al-Saif, Hind, Gotkine, Marc, Leigh, Fawn, Chang, Irene J, Perlman, Seth J, Glass, Ian, Scott, Anna I, Shaw, Christopher E, Basak, A Nazli, Landers, John E, Chiò, Adriano, Crawford, Thomas O, Smith, Bradley N, Traynor, Bryan J, Fallini, Claudia, Gkazi, Athina Soragia, Scotter, Emma L, Kenna, Kevin P, Keagle, Pamela, Tiloca, Cinzia, Vance, Caroline, Colombrita, Claudia, King, Andrew, Pensato, Viviana, Castellotti, Barbara, Baas, Frank, Ten Asbroek, Anneloor L M A, McKenna-Yasek, Diane, McLaughlin, Russell L, Polak, Meraida, Asress, Seneshaw, Esteban-Pérez, Jesús, Stevic, Zorica, D'Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P, Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, van Rheenen, Wouter, Rademakers, Rosa, van Blitterswijk, Marka, Lauria, Giuseppe, Duga, Stefano, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, Sorarù, Gianni, Williams, Kelly L, Nicholson, Garth A, Leblond-Manry, Claire, Rouleau, Guy A, Hardiman, Orla, Veldink, Jan H, van den Berg, Leonard H, Pall, Hardev, Turner, Martin R, Talbot, Kevin, Taroni, Franco, García-Redondo, Alberto, Wu, Zheyang, Glass, Jonathan D, Ratti, Antonia, Adeleye, Adelani, Soltis, Anthony R, Alba, Camille, Viollet, Coralie, Bacikova, Dagmar, Hupalo, Daniel N, Sukumar, Gauthaman, Pollard, Harvey B, Wilkerson, Matthew D, Martinez, Elisa McGrath, Ahmed, Sarah, Arepalli, Sampath, Baloh, Robert H, Bowser, Robert, Brady, Christopher B, Brice, Alexis, Broach, James, Campbell, Roy H, Camu, William, Cooper-Knock, John, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E, Dunckley, Travis L, Eicher, John D, England, Bryce K, Faghri, Faraz, Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro, Geiger, Joshua T, Gerhard, Glenn, Gibson, Summer B, Hardy, John, Harms, Matthew B, Heiman-Patterson, Terry D, Hernandez, Dena G, Jansson, Lilja, Kirby, Janine, Kowall, Neil W, Laaksovirta, Hannu, Landeck, Natalie, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel J L, Maragakis, Nicholas J, Mouzat, Kevin, Murphy, Natalie A, Myllykangas, Liisa, Nalls, Mike A, Orrell, Richard W, Ostrow, Lyle W, Pamphlett, Roger, Pickering-Brown, Stuart, Pioro, Erik P, Pletnikova, Olga, Pliner, Hannah A, Pulst, Stefan M, Ravits, John M, Rivera, Alberto, Robberecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D, Scholz, Sonja W, Sendtner, Michael, Sidle, Katie C, Simmons, Zachary, Singleton, Andrew B, Smith, Nathan, Stone, David J, Troncoso, Juan C, Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M, Van Den Bosch, Ludo, Zinman, Lorne, Angelocola, Stefania M, Ausiello, Francesco P, Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Bersano, Enrica, Bisogni, Giulia, Borghero, Giuseppe, Brunetti, Maura, Cabona, Corrado, Canale, Fabrizio, Canosa, Antonio, Cantisani, Teresa A, Capasso, Margherita, Caponnetto, Claudia, Cardinali, Patrizio, Carrera, Paola, Casale, Federico, Colletti, Tiziana, Conforti, Francesca L, Conte, Amelia, Conti, Elisa, Corbo, Massimo, Cuccu, Stefania, Dalla Bella, Eleonora, D'Errico, Eustachio, DeMarco, Giovanni, Dubbioso, Raffaele, Ferrarese, Carlo, Ferraro, Pilar M, Filippi, Massimo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Gallone, Salvatore, Gianferrari, Giulia, Giannini, Fabio, Grassano, Maurizio, Greco, Lucia, Iazzolino, Barbara, Introna, Alessandro, La Bella, Vincenzo, Lattante, Serena, Liguori, Rocco, Logroscino, Giancarlo, Logullo, Francesco O, Lunetta, Christian, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Manganelli, Fiore, Marangi, Giuseppe, Marinou, Kalliopi, Marrosu, Maria Giovanna, Martinelli, Ilaria, Messina, Sonia, Moglia, Cristina, Mosca, Lorena, Murru, Maria R, Origone, Paola, Passaniti, Carla, Petrelli, Cristina, Petrucci, Antonio, Pozzi, Susanna, Pugliatti, Maura, Quattrini, Angelo, Ricci, Claudia, Riolo, Giulia, Riva, Nilo, Russo, Massimo, Sabatelli, Mario, Salamone, Paolina, Salivetto, Marco, Salvi, Fabrizio, Santarelli, Marialuisa, Sbaiz, Luca, Sideri, Riccardo, Simone, Isabella, Simonini, Cecilia, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Ticca, Anna, Torriello, Antonella, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Vasta, Rosario, Vacchiano, Veria, Vita, Giuseppe, Volanti, Paolo, Zollino, Marcella, Zucchi, Elisabetta, Johnson, J, Chia, R, Miller, D, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, A, Topp, S, Gibbs, J, Cookson, M, Sabir, M, Dalgard, C, Troakes, C, Jones, A, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, I, Dobson-Stone, C, Kwok, J, Bonkowski, E, Palvadeau, R, Tienari, P, Morrison, K, Shaw, P, Al-Chalabi, A, Brown, R, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, I, Perlman, S, Glass, I, Scott, A, Shaw, C, Basak, A, Landers, J, Chiò, A, Crawford, T, Smith, B, Traynor, B, Fallini, C, Gkazi, A, Scotter, E, Kenna, K, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, Ten Asbroek, A, McKenna-Yasek, D, Mclaughlin, R, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D'Alfonso, S, Mazzini, L, Comi, G, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, K, Nicholson, G, Leblond-Manry, C, Rouleau, G, Hardiman, O, Veldink, J, van den Berg, L, Pall, H, Turner, M, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, J, Ratti, A, Adeleye, A, Soltis, A, Alba, C, Viollet, C, Bacikova, D, Hupalo, D, Sukumar, G, Pollard, H, Wilkerson, M, Martinez, E, Ahmed, S, Arepalli, S, Baloh, R, Bowser, R, Brady, C, Brice, A, Broach, J, Campbell, R, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, V, Dunckley, T, Eicher, J, England, B, Faghri, F, Feldman, E, Floeter, M, Fratta, P, Geiger, J, Gerhard, G, Gibson, S, Hardy, J, Harms, M, Heiman-Patterson, T, Hernandez, D, Jansson, L, Kirby, J, Kowall, N, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, Macgowan, D, Maragakis, N, Mouzat, K, Murphy, N, Myllykangas, L, Nalls, M, Orrell, R, Ostrow, L, Pamphlett, R, Pickering-Brown, S, Pioro, E, Pletnikova, O, Pliner, H, Pulst, S, Ravits, J, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, J, Scholz, S, Sendtner, M, Sidle, K, Simmons, Z, Singleton, A, Smith, N, Stone, D, Troncoso, J, Valori, M, Van Damme, P, Van Deerlin, V, Van Den Bosch, L, Zinman, L, Angelocola, S, Ausiello, F, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, T, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, F, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D'Errico, E, Demarco, G, Dubbioso, R, Ferrarese, C, Ferraro, P, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, F, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, M, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, M, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, Johnson, Janel O, Chia, Ruth, Miller, Danny E, Li, Rachel, Kumaran, Ravindran, Abramzon, Yevgeniya, Alahmady, Nada, Renton, Alan E, Topp, Simon D, Gibbs, J Raphael, Cookson, Mark R, Sabir, Marya S, Dalgard, Clifton L, Troakes, Claire, Jones, Ashley R, Shatunov, Aleksey, Iacoangeli, Alfredo, Al Khleifat, Ahmad, Ticozzi, Nicola, Silani, Vincenzo, Gellera, Cinzia, Blair, Ian P, Dobson-Stone, Carol, Kwok, John B, Bonkowski, Emily S, Palvadeau, Robin, Tienari, Pentti J, Morrison, Karen E, Shaw, Pamela J, Al-Chalabi, Ammar, Brown, Robert H, Calvo, Andrea, Mora, Gabriele, Al-Saif, Hind, Gotkine, Marc, Leigh, Fawn, Chang, Irene J, Perlman, Seth J, Glass, Ian, Scott, Anna I, Shaw, Christopher E, Basak, A Nazli, Landers, John E, Chiò, Adriano, Crawford, Thomas O, Smith, Bradley N, Traynor, Bryan J, Fallini, Claudia, Gkazi, Athina Soragia, Scotter, Emma L, Kenna, Kevin P, Keagle, Pamela, Tiloca, Cinzia, Vance, Caroline, Colombrita, Claudia, King, Andrew, Pensato, Viviana, Castellotti, Barbara, Baas, Frank, Ten Asbroek, Anneloor L M A, McKenna-Yasek, Diane, McLaughlin, Russell L, Polak, Meraida, Asress, Seneshaw, Esteban-Pérez, Jesús, Stevic, Zorica, D'Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P, Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, van Rheenen, Wouter, Rademakers, Rosa, van Blitterswijk, Marka, Lauria, Giuseppe, Duga, Stefano, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, Sorarù, Gianni, Williams, Kelly L, Nicholson, Garth A, Leblond-Manry, Claire, Rouleau, Guy A, Hardiman, Orla, Veldink, Jan H, van den Berg, Leonard H, Pall, Hardev, Turner, Martin R, Talbot, Kevin, Taroni, Franco, García-Redondo, Alberto, Wu, Zheyang, Glass, Jonathan D, Ratti, Antonia, Adeleye, Adelani, Soltis, Anthony R, Alba, Camille, Viollet, Coralie, Bacikova, Dagmar, Hupalo, Daniel N, Sukumar, Gauthaman, Pollard, Harvey B, Wilkerson, Matthew D, Martinez, Elisa McGrath, Ahmed, Sarah, Arepalli, Sampath, Baloh, Robert H, Bowser, Robert, Brady, Christopher B, Brice, Alexis, Broach, James, Campbell, Roy H, Camu, William, Cooper-Knock, John, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E, Dunckley, Travis L, Eicher, John D, England, Bryce K, Faghri, Faraz, Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro, Geiger, Joshua T, Gerhard, Glenn, Gibson, Summer B, Hardy, John, Harms, Matthew B, Heiman-Patterson, Terry D, Hernandez, Dena G, Jansson, Lilja, Kirby, Janine, Kowall, Neil W, Laaksovirta, Hannu, Landeck, Natalie, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel J L, Maragakis, Nicholas J, Mouzat, Kevin, Murphy, Natalie A, Myllykangas, Liisa, Nalls, Mike A, Orrell, Richard W, Ostrow, Lyle W, Pamphlett, Roger, Pickering-Brown, Stuart, Pioro, Erik P, Pletnikova, Olga, Pliner, Hannah A, Pulst, Stefan M, Ravits, John M, Rivera, Alberto, Robberecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D, Scholz, Sonja W, Sendtner, Michael, Sidle, Katie C, Simmons, Zachary, Singleton, Andrew B, Smith, Nathan, Stone, David J, Troncoso, Juan C, Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M, Van Den Bosch, Ludo, Zinman, Lorne, Angelocola, Stefania M, Ausiello, Francesco P, Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Bersano, Enrica, Bisogni, Giulia, Borghero, Giuseppe, Brunetti, Maura, Cabona, Corrado, Canale, Fabrizio, Canosa, Antonio, Cantisani, Teresa A, Capasso, Margherita, Caponnetto, Claudia, Cardinali, Patrizio, Carrera, Paola, Casale, Federico, Colletti, Tiziana, Conforti, Francesca L, Conte, Amelia, Conti, Elisa, Corbo, Massimo, Cuccu, Stefania, Dalla Bella, Eleonora, D'Errico, Eustachio, DeMarco, Giovanni, Dubbioso, Raffaele, Ferrarese, Carlo, Ferraro, Pilar M, Filippi, Massimo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Gallone, Salvatore, Gianferrari, Giulia, Giannini, Fabio, Grassano, Maurizio, Greco, Lucia, Iazzolino, Barbara, Introna, Alessandro, La Bella, Vincenzo, Lattante, Serena, Liguori, Rocco, Logroscino, Giancarlo, Logullo, Francesco O, Lunetta, Christian, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Manganelli, Fiore, Marangi, Giuseppe, Marinou, Kalliopi, Marrosu, Maria Giovanna, Martinelli, Ilaria, Messina, Sonia, Moglia, Cristina, Mosca, Lorena, Murru, Maria R, Origone, Paola, Passaniti, Carla, Petrelli, Cristina, Petrucci, Antonio, Pozzi, Susanna, Pugliatti, Maura, Quattrini, Angelo, Ricci, Claudia, Riolo, Giulia, Riva, Nilo, Russo, Massimo, Sabatelli, Mario, Salamone, Paolina, Salivetto, Marco, Salvi, Fabrizio, Santarelli, Marialuisa, Sbaiz, Luca, Sideri, Riccardo, Simone, Isabella, Simonini, Cecilia, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Ticca, Anna, Torriello, Antonella, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Vasta, Rosario, Vacchiano, Veria, Vita, Giuseppe, Volanti, Paolo, Zollino, Marcella, and Zucchi, Elisabetta
Abstract: Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective: To identify the genetic variants associated with juvenile ALS. Design, setting, and participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main outcomes and measures: De novo variants present only in the index case and not in unaffected family members. Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis
Published: 2021

16. HFE p.H63D polymorphism does not influence ALS phenotype and survival

Author: Chiò, Adriano, Mora, Gabriele, Sabatelli, Mario, Caponnetto, Claudia, Lunetta, Christian, Traynor, Bryan J., Johnson, Janel O., Nalls, Mike A., Calvo, Andrea, Moglia, Cristina, Borghero, Giuseppe, Monsurrò, Maria Rosaria, La Bella, Vincenzo, Volanti, Paolo, Simone, Isabella, Salvi, Fabrizio, Logullo, Francesco O., Nilo, Riva, Giannini, Fabio, Mandrioli, Jessica, Tanel, Raffaella, Murru, Maria Rita, Mandich, Paola, Zollino, Marcella, Conforti, Francesca L., Penco, Silvana, Brunetti, Maura, Barberis, Marco, and Restagno, Gabriella
Published: 2015
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17. CHCH10 mutations in an Italian cohort of familial and sporadic amyotrophic lateral sclerosis patients

Author: Chiò, Adriano, Mora, Gabriele, Sabatelli, Mario, Caponnetto, Claudia, Traynor, Bryan J., Johnson, Janel O., Nalls, Mike A., Calvo, Andrea, Moglia, Cristina, Borghero, Giuseppe, Monsurrò, Maria Rosaria, La Bella, Vincenzo, Volanti, Paolo, Simone, Isabella, Salvi, Fabrizio, Logullo, Francesco O., Nilo, Riva, Battistini, Stefania, Mandrioli, Jessica, Tanel, Raffaella, Murru, Maria Rita, Mandich, Paola, Zollino, Marcella, Conforti, Francesca L., Brunetti, Maura, Barberis, Marco, Restagno, Gabriella, Penco, Silvana, and Lunetta, Christian
Published: 2015
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18. A small deletion in C9orf72 hides a proportion of expansion carriers in FTLD

Author: Rollinson, Sara, Bennion Callister, Janis, Young, Kate, Ryan, Sarah J., Druyeh, Ronald, Rohrer, Jonathan D., Snowden, Julie, Richardson, Anna, Jones, Matt, Harris, Jenny, Davidson, Yvonne, Robinson, Andrew, Ealing, John, Johnson, Janel O., Traynor, Bryan, Mead, Simon, Mann, David, and Pickering-Brown, Stuart M.
Published: 2015
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19. Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease

Author: Johnson, Janel O., Gibbs, J. Raphael, Megarbane, Andre, Urtizberea, J. Andoni, Hernandez, Dena G., Foley, A. Reghan, Arepalli, Sampath, Pandraud, Amelie, Simón-Sánchez, Javier, Clayton, Peter, Reilly, Mary M., Muntoni, Francesco, Abramzon, Yevgeniya, Houlden, Henry, and Singleton, Andrew B.
Published: 2012
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20. Large Proportion of Amyotrophic Lateral Sclerosis Cases in Sardinia Due to a Single Founder Mutation of the TARDBP Gene

Author: Chiò, Adriano, Borghero, Giuseppe, Pugliatti, Maura, Ticca, Anna, Calvo, Andrea, Moglia, Cristina, Mutani, Roberto, Brunetti, Maura, Ossola, Irene, Marrosu, Maria Giovanna, Murru, Maria Rita, Floris, Gianluca, Cannas, Antonino, Parish, Leslie D., Cossu, Paola, Abramzon, Yevgeniya, Johnson, Janel O., Nalls, Michael A., Arepalli, Sampath, Chong, Sean, Hernandez, Dena G., Traynor, Bryan J., and Restagno, Gabriella
Published: 2011
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21. SCA15 Due to Large ITPR1 Deletions in a Cohort of 333 White Families With Dominant Ataxia

Author: Marelli, Cecilia, van de Leemput, Joyce, Johnson, Janel O., Tison, Francois, Thauvin-Robinet, Christel, Picard, Fabienne, Tranchant, Christine, Hernandez, Dena G., Huttin, Bernard, Boulliat, Jacques, Sangla, Iban, Marescaux, Christian, Brique, Serge, Dollfus, Hélène, Arepalli, Sampath, Benatru, Isabelle, Ollagnon, Elisabeth, Forlani, Sylvie, Hardy, John, Stevanin, Giovanni, Dürr, Alexandra, Singleton, Andrew, and Brice, Alexis
Published: 2011
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22. Smoking-responsive juvenile-onset Parkinsonism

Author: Hanagasi, Hasmet Ayhan, Lees, Andrew, Johnson, Janel O., Singleton, Andrew, and Emre, Murat
Published: 2007
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23. Parkin disease in a Brazilian kindred: Manifesting heterozygotes and clinical follow-up over 10 years

Author: Khan, Naheed L., Horta, Wagner, Eunson, Louise, Graham, Elizabeth, Johnson, Janel O., Chang, Shannon, Davis, Mary, Singleton, Andrew, Wood, Nicholas W., and Lees, Andrew J.
Published: 2005
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24. Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis.

Author: Johnson, Janel O., Chia, Ruth, Miller, Danny E., Li, Rachel, Kumaran, Ravindran, Abramzon, Yevgeniya, Alahmady, Nada, Renton, Alan E., Topp, Simon D., Gibbs, J. Raphael, Cookson, Mark R., Sabir, Marya S., Dalgard, Clifton L., Troakes, Claire, Jones, Ashley R., Shatunov, Aleksey, Iacoangeli, Alfredo, Al Khleifat, Ahmad, Ticozzi, Nicola, and Silani, Vincenzo
Published: 2021
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25. Valosin-containing protein (VCP) mutations in sporadic amyotrophic lateral sclerosis

Author: Abramzon, Yevgeniya, Johnson, Janel O., Scholz, Sonja W., Taylor, J.P., Brunetti, Maura, Calvo, Andrea, Mandrioli, Jessica, Benatar, Michael, Mora, Gabriele, Restagno, Gabriella, Chiò, Adriano, and Traynor, Bryan J.
Published: 2012
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26. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

Author: Nicolas, Aude, Kenna, Kevin P., Renton, Alan E., Ticozzi, Nicola, Faghri, Faraz, Chia, Ruth, Dominov, Janice A., Kenna, Brendan J., Nalls, Mike A., Keagle, Pamela, Rivera, Alberto M., van Rheenen, Wouter, Murphy, Natalie A., van Vugt, Joke J. F. A., Geiger, Joshua T., van der Spek, Rick A., Pliner, Hannah A., Shankaracharya, Smith, Bradley N., Marangi, Giuseppe, Topp, Simon D., Abramzon, Yevgeniya, Gkazi, Athina Soragia, Eicher, John D., Kenna, Aoife, Mora, Gabriele, Calvo, Andrea, Mazzini, Letizia, Riva, Nilo, Mandrioli, Jessica, Caponnetto, Claudia, Battistini, Stefania, Volanti, Paolo, La Bella, Vincenzo, Conforti, Francesca L., Borghero, Giuseppe, Messina, Sonia, Simone, Isabella L., Trojsi, Francesca, Salvi, Fabrizio, Logullo, Francesco O., D'Alfonso, Sandra, Corrado, Lucia, Capasso, Margherita, Ferrucci, Luigi, Moreno, Cristiane de Araujo Martins, Kamalakaran, Sitharthan, Goldstein, David B., Gitler, Aaron D., Harris, Tim, Myers, Richard M., Phatnani, Hemali, Musunuri, Rajeeva Lochan, Evani, Uday Shankar, Abhyankar, Avinash, Zody, Michael C., Kaye, Julia, Finkbeiner, Steven, Wyman, Stacia K., LeNail, Alex, Lima, Leandro, Fraenkel, Ernest, Svendsen, Clive N., Thompson, Leslie M., Van Eyk, Jennifer E., Berry, James D., Miller, Timothy M., Kolb, Stephen J., Cudkowicz, Merit, Baxi, Emily, Benatar, Michael, Taylor, J. Paul, Rampersaud, Evadnie, Wu, Gang, Wuu, Joanne, Lauria, Giuseppe, Verde, Federico, Fogh, Isabella, Tiloca, Cinzia, Comi, Giacomo P., Soraru, Gianni, Cereda, Cristina, Corcia, Philippe, Laaksovirta, Hannu, Myllykangas, Liisa, Jansson, Lilja, Valori, Miko, Ealing, John, Hamdalla, Hisham, Rollinson, Sara, Pickering-Brown, Stuart, Orrell, Richard W., Sidle, Katie C., Malaspina, Andrea, Hardy, John, Singleton, Andrew B., Johnson, Janel O., Arepalli, Sampath, Sapp, Peter C., McKenna-Yasek, Diane, Polak, Meraida, Asress, Seneshaw, Al-Sarraj, Safa, King, Andrew, Troakes, Claire, Vance, Caroline, de Belleroche, Jacqueline, Baas, Frank, ten Asbroek, Anneloor L. M. A., Luis Munoz-Blanco, Jose, Hernandez, Dena G., Ding, Jinhui, Gibbs, J. Raphael, Scholz, Sonja W., Floeter, Mary Kay, Campbell, Roy H., Landi, Francesco, Bowser, Robert, Pulst, Stefan M., Ravits, John M., 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, Mouzat, Kevin, Lumbroso, Serge, Heiman-Patterson, Terry D., Kamel, Freya, Van Den Bosch, Ludo, Baloh, Robert H., Strom, Tim M., Meitinger, Thomas, Shatunov, Aleksey, Van Eijk, Kristel R., de Carvalho, Mamede, Kooyman, Maarten, Middelkoop, Bas, Moisse, Matthieu, McLaughlin, Russell L., Van Es, Michael A., Weber, Markus, Boylan, Kevin B., Van Blitterswijk, Marka, Rademakers, Rosa, Morrison, Karen E., Basak, A. Nazli, Mora, Jesus S., Drory, Vivian E., Shaw, Pamela J., Turner, Martin R., Talbot, Kevin, Hardiman, Orla, Williams, Kelly L., Fifita, Jennifer A., Nicholson, Garth A., Blair, Ian P., Rouleau, Guy A., Esteban-Perez, Jesus, Garcia-Redondo, Alberto, Al-Chalabi, Ammar, Rogaeva, Ekaterina, Zinman, Lorne, Ostrow, Lyle W., Maragakis, Nicholas J., Rothstein, Jeffrey D., Simmons, Zachary, Cooper-Knock, Johnathan, Brice, Alexis, Goutman, Stephen A., Feldman, Eva L., Gibson, Summer B., Taroni, Franco, Ratti, Antonia, Gellera, Cinzia, Van Damme, Philip, Robberecht, Wim, Fratta, Pietro, Sabatelli, Mario, Lunetta, Christian, Ludolph, Albert C., Andersen, Peter M., Weishaupt, Jochen H., Camu, William, Trojanowski, John Q., Van Deerlin, Vivianna M., Brown, Robert H., Jr., van den Berg, Leonard H., Veldink, Jan H., Harms, Matthew B., Glass, Jonathan D., Stone, David J., Tienari, Pentti, Silani, Vincenzo, Chio, Adriano, Shaw, Christopher E., Traynor, Bryan J., Landers, John E., Nicolas, Aude, Kenna, Kevin P., Renton, Alan E., Ticozzi, Nicola, Faghri, Faraz, Chia, Ruth, Dominov, Janice A., Kenna, Brendan J., Nalls, Mike A., Keagle, Pamela, Rivera, Alberto M., van Rheenen, Wouter, Murphy, Natalie A., van Vugt, Joke J. F. A., Geiger, Joshua T., van der Spek, Rick A., Pliner, Hannah A., Shankaracharya, Smith, Bradley N., Marangi, Giuseppe, Topp, Simon D., Abramzon, Yevgeniya, Gkazi, Athina Soragia, Eicher, John D., Kenna, Aoife, Mora, Gabriele, Calvo, Andrea, Mazzini, Letizia, Riva, Nilo, Mandrioli, Jessica, Caponnetto, Claudia, Battistini, Stefania, Volanti, Paolo, La Bella, Vincenzo, Conforti, Francesca L., Borghero, Giuseppe, Messina, Sonia, Simone, Isabella L., Trojsi, Francesca, Salvi, Fabrizio, Logullo, Francesco O., D'Alfonso, Sandra, Corrado, Lucia, Capasso, Margherita, Ferrucci, Luigi, Moreno, Cristiane de Araujo Martins, Kamalakaran, Sitharthan, Goldstein, David B., Gitler, Aaron D., Harris, Tim, Myers, Richard M., Phatnani, Hemali, Musunuri, Rajeeva Lochan, Evani, Uday Shankar, Abhyankar, Avinash, Zody, Michael C., Kaye, Julia, Finkbeiner, Steven, Wyman, Stacia K., LeNail, Alex, Lima, Leandro, Fraenkel, Ernest, Svendsen, Clive N., Thompson, Leslie M., Van Eyk, Jennifer E., Berry, James D., Miller, Timothy M., Kolb, Stephen J., Cudkowicz, Merit, Baxi, Emily, Benatar, Michael, Taylor, J. Paul, Rampersaud, Evadnie, Wu, Gang, Wuu, Joanne, Lauria, Giuseppe, Verde, Federico, Fogh, Isabella, Tiloca, Cinzia, Comi, Giacomo P., Soraru, Gianni, Cereda, Cristina, Corcia, Philippe, Laaksovirta, Hannu, Myllykangas, Liisa, Jansson, Lilja, Valori, Miko, Ealing, John, Hamdalla, Hisham, Rollinson, Sara, Pickering-Brown, Stuart, Orrell, Richard W., Sidle, Katie C., Malaspina, Andrea, Hardy, John, Singleton, Andrew B., Johnson, Janel O., Arepalli, Sampath, Sapp, Peter C., McKenna-Yasek, Diane, Polak, Meraida, Asress, Seneshaw, Al-Sarraj, Safa, King, Andrew, Troakes, Claire, Vance, Caroline, de Belleroche, Jacqueline, Baas, Frank, ten Asbroek, Anneloor L. M. A., Luis Munoz-Blanco, Jose, Hernandez, Dena G., Ding, Jinhui, Gibbs, J. Raphael, Scholz, Sonja W., Floeter, Mary Kay, Campbell, Roy H., Landi, Francesco, Bowser, Robert, Pulst, Stefan M., Ravits, John M., 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, Mouzat, Kevin, Lumbroso, Serge, Heiman-Patterson, Terry D., Kamel, Freya, Van Den Bosch, Ludo, Baloh, Robert H., Strom, Tim M., Meitinger, Thomas, Shatunov, Aleksey, Van Eijk, Kristel R., de Carvalho, Mamede, Kooyman, Maarten, Middelkoop, Bas, Moisse, Matthieu, McLaughlin, Russell L., Van Es, Michael A., Weber, Markus, Boylan, Kevin B., Van Blitterswijk, Marka, Rademakers, Rosa, Morrison, Karen E., Basak, A. Nazli, Mora, Jesus S., Drory, Vivian E., Shaw, Pamela J., Turner, Martin R., Talbot, Kevin, Hardiman, Orla, Williams, Kelly L., Fifita, Jennifer A., Nicholson, Garth A., Blair, Ian P., Rouleau, Guy A., Esteban-Perez, Jesus, Garcia-Redondo, Alberto, Al-Chalabi, Ammar, Rogaeva, Ekaterina, Zinman, Lorne, Ostrow, Lyle W., Maragakis, Nicholas J., Rothstein, Jeffrey D., Simmons, Zachary, Cooper-Knock, Johnathan, Brice, Alexis, Goutman, Stephen A., Feldman, Eva L., Gibson, Summer B., Taroni, Franco, Ratti, Antonia, Gellera, Cinzia, Van Damme, Philip, Robberecht, Wim, Fratta, Pietro, Sabatelli, Mario, Lunetta, Christian, Ludolph, Albert C., Andersen, Peter M., Weishaupt, Jochen H., Camu, William, Trojanowski, John Q., Van Deerlin, Vivianna M., Brown, Robert H., Jr., van den Berg, Leonard H., Veldink, Jan H., Harms, Matthew B., Glass, Jonathan D., Stone, David J., Tienari, Pentti, Silani, Vincenzo, Chio, Adriano, Shaw, Christopher E., Traynor, Bryan J., and Landers, John E.
Abstract: To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
Published: 2018
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27. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

Author: Nicolas, A, Kenna, K, Renton, A, Ticozzi, N, Faghri, F, Chia, R, Dominov, J, Kenna, B, Nalls, M, Keagle, P, Rivera, A, van Rheenen, W, Murphy, N, van Vugt, J, Geiger, J, van der Spek, R, Pliner, H, Shankaracharya, N, Smith, B, Marangi, G, Topp, S, Abramzon, Y, Gkazi, A, Eicher, J, Kenna, A, Logullo, F, Simone, I, Logroscino, G, Salvi, F, Bartolomei, I, Borghero, G, Murru, M, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M, Floris, G, Cannas, A, Capasso, M, Caponnetto, C, Mancardi, G, Origone, P, Mandich, P, Conforti, F, Cavallaro, S, Mora, G, Marinou, K, Sideri, R, Penco, S, Mosca, L, Lunetta, C, Pinter, G, Corbo, M, Riva, N, Carrera, P, Volanti, P, Mandrioli, J, Fini, N, Fasano, A, Tremolizzo, L, Arosio, A, Ferrarese, C, Trojsi, F, Tedeschi, G, Monsurrò, M, Piccirillo, G, Femiano, C, Ticca, A, Ortu, E, La Bella, V, Spataro, R, Colletti, T, Sabatelli, M, Zollino, M, Conte, A, Luigetti, M, Lattante, S, Santarelli, M, Petrucci, A, Pugliatti, M, Pirisi, A, Parish, L, Occhineri, P, Giannini, F, Battistini, S, Ricci, C, Benigni, M, Cau, T, Loi, D, Calvo, A, Moglia, C, Brunetti, M, Barberis, M, Restagno, G, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Canosa, A, Ilardi, A, Manera, U, Grassano, M, Tanel, R, Pisano, F, Mazzini, L, Messina, S, D'Alfonso, S, Corrado, L, Ferrucci, L, Harms, M, Goldstein, D, Shneider, N, Goutman, S, Simmons, Z, Miller, T, Chandran, S, Pal, S, Manousakis, G, Appel, S, Simpson, E, Wang, L, Baloh, R, Gibson, S, Bedlack, R, Lacomis, D, Sareen, D, Sherman, A, Bruijn, L, Penny, M, Moreno, C, Kamalakaran, S, Allen, A, Boone, B, Brown, R, Carulli, J, Chesi, A, Chung, W, Cirulli, E, Cooper, G, Couthouis, J, Day-Williams, A, Dion, P, Gitler, A, Glass, J, Han, Y, Harris, T, Hayes, S, Jones, A, Keebler, J, Krueger, B, Lasseigne, B, Levy, S, Lu, Y, Maniatis, T, McKenna-Yasek, D, Myers, R, Petrovski, S, Pulst, S, Raphael, A, Ravits, J, Ren, Z, Rouleau, G, Sapp, P, Sims, K, Staropoli, J, Waite, L, Wang, Q, Wimbish, J, Xin, W, Phatnani, H, Kwan, J, Broach, J, Arcila-Londono, X, Lee, E, Van Deerlin, V, Fraenkel, E, Ostrow, L, Baas, F, Zaitlen, N, Berry, J, Malaspina, A, Fratta, P, Cox, G, Thompson, L, Finkbeiner, S, Dardiotis, E, Hornstein, E, Macgowan, D, Heiman-Patterson, T, Hammell, M, Patsopoulos, N, Dubnau, J, Nath, A, Musunuri, R, Evani, U, Abhyankar, A, Zody, M, Kaye, J, Wyman, S, Lenail, A, Lima, L, Rothstein, J, Svendsen, C, Van Eyk, J, Maragakis, N, Kolb, S, Cudkowicz, M, Baxi, E, Benatar, M, Taylor, J, Wu, G, Rampersaud, E, Wuu, J, Rademakers, R, Züchner, S, Schule, R, Mccauley, J, Hussain, S, Cooley, A, Wallace, M, Clayman, C, Barohn, R, Statland, J, Swenson, A, Jackson, C, Trivedi, J, Khan, S, Katz, J, Jenkins, L, Burns, T, Gwathmey, K, Caress, J, Mcmillan, C, Elman, L, Pioro, E, Heckmann, J, So, Y, Walk, D, Maiser, S, Zhang, J, Silani, V, Gellera, C, Ratti, A, Taroni, F, Lauria, G, Verde, F, Fogh, I, Tiloca, C, Comi, G, Sorarù, G, Cereda, C, De Marchi, F, Corti, S, Ceroni, M, Siciliano, G, Filosto, M, Inghilleri, M, Peverelli, S, Colombrita, C, Poletti, B, Maderna, L, Del Bo, R, Gagliardi, S, Querin, G, Bertolin, C, Pensato, V, Castellotti, B, Camu, W, Mouzat, K, Lumbroso, S, Corcia, P, Meininger, V, Besson, G, Lagrange, E, Clavelou, P, Guy, N, Couratier, P, Vourch, P, Danel, V, Bernard, E, Lemasson, G, Laaksovirta, H, Myllykangas, L, Jansson, L, Valori, M, Ealing, J, Hamdalla, H, Rollinson, S, Pickering-Brown, S, Orrell, R, Sidle, K, Hardy, J, Singleton, A, Johnson, J, Arepalli, S, Polak, M, Asress, S, Al-Sarraj, S, King, A, Troakes, C, Vance, C, de Belleroche, J, ten Asbroek, A, Muñoz-Blanco, J, Hernandez, D, Ding, J, Gibbs, J, Scholz, S, Floeter, M, Campbell, R, Landi, F, Bowser, R, Kirby, J, Pamphlett, R, Gerhard, G, Dunckley, T, Brady, C, Kowall, N, Troncoso, J, Le Ber, I, Kamel, F, Van Den Bosch, L, Strom, T, Meitinger, T, Shatunov, A, Van Eijk, K, de Carvalho, M, Kooyman, M, Middelkoop, B, Moisse, M, Mclaughlin, R, Van Es, M, Weber, M, Boylan, K, Van Blitterswijk, M, Morrison, K, Basak, A, Mora, J, Drory, V, Shaw, P, Turner, M, Talbot, K, Hardiman, O, Williams, K, Fifita, J, Nicholson, G, Blair, I, Esteban-Pérez, J, García-Redondo, A, Al-Chalabi, A, Al Kheifat, A, Andersen, P, Chio, A, Cooper-Knock, J, Dekker, A, Redondo, A, Gotkine, M, Hide, W, Iacoangeli, A, Kiernan, M, Landers, J, Mill, J, Neto, M, Pardina, J, Newhouse, S, Pinto, S, Pulit, S, Robberecht, W, Shaw, C, Sproviero, W, Tazelaar, G, van Damme, P, van den Berg, L, van Eijk, K, van Es, M, Veldink, J, Zatz, M, Bauer, D, Twine, N, Rogaeva, E, Zinman, L, Brice, A, Feldman, E, Ludolph, A, Weishaupt, J, Trojanowski, J, Stone, D, Tienari, P, Chiò, A, Traynor, B, Nicolas, Aude, Kenna, Kevin P., Renton, Alan E., Ticozzi, Nicola, Faghri, Faraz, Chia, Ruth, Dominov, Janice A., Kenna, Brendan J., Nalls, Mike A., Keagle, Pamela, Rivera, Alberto M., van Rheenen, Wouter, Murphy, Natalie A., van Vugt, Joke J. F. A., Geiger, Joshua T., van der Spek, Rick, Pliner, Hannah A., Shankaracharya, null, Smith, Bradley N., Marangi, Giuseppe, Topp, Simon D., Abramzon, Yevgeniya, Gkazi, Athina Soragia, Eicher, John D., Kenna, Aoife, 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, 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, Mazzini, Letizia, Messina, Sonia, D'Alfonso, Sandra, Corrado, Lucia, Ferrucci, Luigi, Harms, Matthew B., Goldstein, David B., Shneider, Neil A., Goutman, Stephen, Simmons, Zachary, Miller, Timothy M., Chandran, Siddharthan, Pal, Suvankar, Manousakis, George, Appel, Stanley, Simpson, Ericka, Wang, Leo, Baloh, Robert H., Gibson, Summer, Bedlack, Richard S., Lacomis, David, Sareen, Dhruv, Sherman, Alexander, Bruijn, Lucie, Penny, Michelle, Moreno, Cristiane de Araujo Martins, Kamalakaran, Sitharthan, Allen, Andrew 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, Steven, Dardiotis, Efthimios, Hornstein, Eran, MacGowan, Daniel J., Heiman-Patterson, Terry, Hammell, Molly G., Patsopoulos, Nikolaos A., Dubnau, Joshua, Nath, Avindra, Musunuri, Rajeeva Lochan, Evani, Uday Shankar, Abhyankar, Avinash, Zody, Michael C., Kaye, Julia, 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, Wyman, Stacia K., Van Eyk, Jennifer E., 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, Gellera, Cinzia, Ratti, Antonia, Taroni, Franco, Lauria, Giuseppe, Verde, Federico, Fogh, Isabella, Tiloca, Cinzia, Comi, Giacomo P., Sorarù, Gianni, Cereda, Cristina, De Marchi, Fabiola, Corti, Stefania, Ceroni, Mauro, 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, 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, Shatunov, Aleksey, Van Eijk, Kristel R., de Carvalho, Mamede, Kooyman, Maarten, Middelkoop, Bas, Moisse, Mattieu, McLaughlin, Russell L., Van Es, Michael A., Weber, Markus, Boylan, Kevin B., Van Blitterswijk, Marka, Morrison, Karen E., Basak, A. Nazli, Mora, Jesús S., Drory, Vivian E., Shaw, Pamela J., Turner, Martin R., Talbot, Kevin, Hardiman, Orla, Williams, Kelly L., Fifita, Jennifer A., Nicholson, Garth A., Blair, Ian P., Esteban-Pérez, Jesús, García-Redondo, Alberto, Al-Chalabi, Ammar, Al Kheifat, Ahmad, Andersen, Peter, Chio, Adriano, Cooper-Knock, Jonathan, Dekker, Annelot, Drory, Vivian, Redondo, Alberto Garcia, Gotkine, Marc, Hide, Winston, Iacoangeli, Alfredo, Glass, Jonathan, Kenna, Kevin, Kiernan, Matthew, Landers, John, McLaughlin, Russell, Mill, Jonathan, Neto, Miguel Mitne, Pardina, Jesus Mora, Morrison, Karen, Newhouse, Stephen, Pinto, Susana, Pulit, Sara, Robberecht, Wim, Shaw, Pamela, Shaw, Chris, Sproviero, William, Tazelaar, Gijs, van Damme, Philip, van den Berg, Leonard, van Eijk, Kristel, van Es, Michael, van Vugt, Joke, Veldink, Jan, Zatz, Mayana, Bauer, Denis C., Twine, Natalie A., Rogaeva, Ekaterina, Zinman, Lorne, Brice, Alexis, Goutman, Stephen A., Feldman, Eva L., Gibson, Summer B., Ludolph, Albert C., Andersen, Peter M., Weishaupt, Jochen H., Trojanowski, John Q., Brown, Robert H., van den Berg, Leonard H., Veldink, Jan H., Stone, David J., Tienari, Pentti, Chiò, Adriano, Shaw, Christopher E., Traynor, Bryan J., Landers, John E., Nicolas, A, Kenna, K, Renton, A, Ticozzi, N, Faghri, F, Chia, R, Dominov, J, Kenna, B, Nalls, M, Keagle, P, Rivera, A, van Rheenen, W, Murphy, N, van Vugt, J, Geiger, J, van der Spek, R, Pliner, H, Shankaracharya, N, Smith, B, Marangi, G, Topp, S, Abramzon, Y, Gkazi, A, Eicher, J, Kenna, A, Logullo, F, Simone, I, Logroscino, G, Salvi, F, Bartolomei, I, Borghero, G, Murru, M, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M, Floris, G, Cannas, A, Capasso, M, Caponnetto, C, Mancardi, G, Origone, P, Mandich, P, Conforti, F, Cavallaro, S, Mora, G, Marinou, K, Sideri, R, Penco, S, Mosca, L, Lunetta, C, Pinter, G, Corbo, M, Riva, N, Carrera, P, Volanti, P, Mandrioli, J, Fini, N, Fasano, A, Tremolizzo, L, Arosio, A, Ferrarese, C, Trojsi, F, Tedeschi, G, Monsurrò, M, Piccirillo, G, Femiano, C, Ticca, A, Ortu, E, La Bella, V, Spataro, R, Colletti, T, Sabatelli, M, Zollino, M, Conte, A, Luigetti, M, Lattante, S, Santarelli, M, Petrucci, A, Pugliatti, M, Pirisi, A, Parish, L, Occhineri, P, Giannini, F, Battistini, S, Ricci, C, Benigni, M, Cau, T, Loi, D, Calvo, A, Moglia, C, Brunetti, M, Barberis, M, Restagno, G, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Canosa, A, Ilardi, A, Manera, U, Grassano, M, Tanel, R, Pisano, F, Mazzini, L, Messina, S, D'Alfonso, S, Corrado, L, Ferrucci, L, Harms, M, Goldstein, D, Shneider, N, Goutman, S, Simmons, Z, Miller, T, Chandran, S, Pal, S, Manousakis, G, Appel, S, Simpson, E, Wang, L, Baloh, R, Gibson, S, Bedlack, R, Lacomis, D, Sareen, D, Sherman, A, Bruijn, L, Penny, M, Moreno, C, Kamalakaran, S, Allen, A, Boone, B, Brown, R, Carulli, J, Chesi, A, Chung, W, Cirulli, E, Cooper, G, Couthouis, J, Day-Williams, A, Dion, P, Gitler, A, Glass, J, Han, Y, Harris, T, Hayes, S, Jones, A, Keebler, J, Krueger, B, Lasseigne, B, Levy, S, Lu, Y, Maniatis, T, McKenna-Yasek, D, Myers, R, Petrovski, S, Pulst, S, Raphael, A, Ravits, J, Ren, Z, Rouleau, G, Sapp, P, Sims, K, Staropoli, J, Waite, L, Wang, Q, Wimbish, J, Xin, W, Phatnani, H, Kwan, J, Broach, J, Arcila-Londono, X, Lee, E, Van Deerlin, V, Fraenkel, E, Ostrow, L, Baas, F, Zaitlen, N, Berry, J, Malaspina, A, Fratta, P, Cox, G, Thompson, L, Finkbeiner, S, Dardiotis, E, Hornstein, E, Macgowan, D, Heiman-Patterson, T, Hammell, M, Patsopoulos, N, Dubnau, J, Nath, A, Musunuri, R, Evani, U, Abhyankar, A, Zody, M, Kaye, J, Wyman, S, Lenail, A, Lima, L, Rothstein, J, Svendsen, C, Van Eyk, J, Maragakis, N, Kolb, S, Cudkowicz, M, Baxi, E, Benatar, M, Taylor, J, Wu, G, Rampersaud, E, Wuu, J, Rademakers, R, Züchner, S, Schule, R, Mccauley, J, Hussain, S, Cooley, A, Wallace, M, Clayman, C, Barohn, R, Statland, J, Swenson, A, Jackson, C, Trivedi, J, Khan, S, Katz, J, Jenkins, L, Burns, T, Gwathmey, K, Caress, J, Mcmillan, C, Elman, L, Pioro, E, Heckmann, J, So, Y, Walk, D, Maiser, S, Zhang, J, Silani, V, Gellera, C, Ratti, A, Taroni, F, Lauria, G, Verde, F, Fogh, I, Tiloca, C, Comi, G, Sorarù, G, Cereda, C, De Marchi, F, Corti, S, Ceroni, M, Siciliano, G, Filosto, M, Inghilleri, M, Peverelli, S, Colombrita, C, Poletti, B, Maderna, L, Del Bo, R, Gagliardi, S, Querin, G, Bertolin, C, Pensato, V, Castellotti, B, Camu, W, Mouzat, K, Lumbroso, S, Corcia, P, Meininger, V, Besson, G, Lagrange, E, Clavelou, P, Guy, N, Couratier, P, Vourch, P, Danel, V, Bernard, E, Lemasson, G, Laaksovirta, H, Myllykangas, L, Jansson, L, Valori, M, Ealing, J, Hamdalla, H, Rollinson, S, Pickering-Brown, S, Orrell, R, Sidle, K, Hardy, J, Singleton, A, Johnson, J, Arepalli, S, Polak, M, Asress, S, Al-Sarraj, S, King, A, Troakes, C, Vance, C, de Belleroche, J, ten Asbroek, A, Muñoz-Blanco, J, Hernandez, D, Ding, J, Gibbs, J, Scholz, S, Floeter, M, Campbell, R, Landi, F, Bowser, R, Kirby, J, Pamphlett, R, Gerhard, G, Dunckley, T, Brady, C, Kowall, N, Troncoso, J, Le Ber, I, Kamel, F, Van Den Bosch, L, Strom, T, Meitinger, T, Shatunov, A, Van Eijk, K, de Carvalho, M, Kooyman, M, Middelkoop, B, Moisse, M, Mclaughlin, R, Van Es, M, Weber, M, Boylan, K, Van Blitterswijk, M, Morrison, K, Basak, A, Mora, J, Drory, V, Shaw, P, Turner, M, Talbot, K, Hardiman, O, Williams, K, Fifita, J, Nicholson, G, Blair, I, Esteban-Pérez, J, García-Redondo, A, Al-Chalabi, A, Al Kheifat, A, Andersen, P, Chio, A, Cooper-Knock, J, Dekker, A, Redondo, A, Gotkine, M, Hide, W, Iacoangeli, A, Kiernan, M, Landers, J, Mill, J, Neto, M, Pardina, J, Newhouse, S, Pinto, S, Pulit, S, Robberecht, W, Shaw, C, Sproviero, W, Tazelaar, G, van Damme, P, van den Berg, L, van Eijk, K, van Es, M, Veldink, J, Zatz, M, Bauer, D, Twine, N, Rogaeva, E, Zinman, L, Brice, A, Feldman, E, Ludolph, A, Weishaupt, J, Trojanowski, J, Stone, D, Tienari, P, Chiò, A, Traynor, B, Nicolas, Aude, Kenna, Kevin P., Renton, Alan E., Ticozzi, Nicola, Faghri, Faraz, Chia, Ruth, Dominov, Janice A., Kenna, Brendan J., Nalls, Mike A., Keagle, Pamela, Rivera, Alberto M., van Rheenen, Wouter, Murphy, Natalie A., van Vugt, Joke J. F. A., Geiger, Joshua T., van der Spek, Rick, Pliner, Hannah A., Shankaracharya, null, Smith, Bradley N., Marangi, Giuseppe, Topp, Simon D., Abramzon, Yevgeniya, Gkazi, Athina Soragia, Eicher, John D., Kenna, Aoife, 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, 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, Mazzini, Letizia, Messina, Sonia, D'Alfonso, Sandra, Corrado, Lucia, Ferrucci, Luigi, Harms, Matthew B., Goldstein, David B., Shneider, Neil A., Goutman, Stephen, Simmons, Zachary, Miller, Timothy M., Chandran, Siddharthan, Pal, Suvankar, Manousakis, George, Appel, Stanley, Simpson, Ericka, Wang, Leo, Baloh, Robert H., Gibson, Summer, Bedlack, Richard S., Lacomis, David, Sareen, Dhruv, Sherman, Alexander, Bruijn, Lucie, Penny, Michelle, Moreno, Cristiane de Araujo Martins, Kamalakaran, Sitharthan, Allen, Andrew 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, Steven, Dardiotis, Efthimios, Hornstein, Eran, MacGowan, Daniel J., Heiman-Patterson, Terry, Hammell, Molly G., Patsopoulos, Nikolaos A., Dubnau, Joshua, Nath, Avindra, Musunuri, Rajeeva Lochan, Evani, Uday Shankar, Abhyankar, Avinash, Zody, Michael C., Kaye, Julia, 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, Wyman, Stacia K., Van Eyk, Jennifer E., 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, Gellera, Cinzia, Ratti, Antonia, Taroni, Franco, Lauria, Giuseppe, Verde, Federico, Fogh, Isabella, Tiloca, Cinzia, Comi, Giacomo P., Sorarù, Gianni, Cereda, Cristina, De Marchi, Fabiola, Corti, Stefania, Ceroni, Mauro, 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, 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, Shatunov, Aleksey, Van Eijk, Kristel R., de Carvalho, Mamede, Kooyman, Maarten, Middelkoop, Bas, Moisse, Mattieu, McLaughlin, Russell L., Van Es, Michael A., Weber, Markus, Boylan, Kevin B., Van Blitterswijk, Marka, Morrison, Karen E., Basak, A. Nazli, Mora, Jesús S., Drory, Vivian E., Shaw, Pamela J., Turner, Martin R., Talbot, Kevin, Hardiman, Orla, Williams, Kelly L., Fifita, Jennifer A., Nicholson, Garth A., Blair, Ian P., Esteban-Pérez, Jesús, García-Redondo, Alberto, Al-Chalabi, Ammar, Al Kheifat, Ahmad, Andersen, Peter, Chio, Adriano, Cooper-Knock, Jonathan, Dekker, Annelot, Drory, Vivian, Redondo, Alberto Garcia, Gotkine, Marc, Hide, Winston, Iacoangeli, Alfredo, Glass, Jonathan, Kenna, Kevin, Kiernan, Matthew, Landers, John, McLaughlin, Russell, Mill, Jonathan, Neto, Miguel Mitne, Pardina, Jesus Mora, Morrison, Karen, Newhouse, Stephen, Pinto, Susana, Pulit, Sara, Robberecht, Wim, Shaw, Pamela, Shaw, Chris, Sproviero, William, Tazelaar, Gijs, van Damme, Philip, van den Berg, Leonard, van Eijk, Kristel, van Es, Michael, van Vugt, Joke, Veldink, Jan, Zatz, Mayana, Bauer, Denis C., Twine, Natalie A., Rogaeva, Ekaterina, Zinman, Lorne, Brice, Alexis, Goutman, Stephen A., Feldman, Eva L., Gibson, Summer B., Ludolph, Albert C., Andersen, Peter M., Weishaupt, Jochen H., Trojanowski, John Q., Brown, Robert H., 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.
Abstract: To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS. Using a large-scale genome-wide association study and exome sequencing, we identified KIF5A as a novel gene associated with ALS. Our data broaden the phenotype resulting from mutations in KIF5A and highlight the importance of cytoskeletal defects in the pathogenesis of ALS.
Published: 2018

28. Exome Sequencing Reveals VCP Mutations as a Cause of Familial ALS

Author: Johnson, Janel O., Mandrioli, Jessica, Benatar, Michael, Abramzon, Yevgeniya, Van Deerlin, Vivianna M., Trojanowski, John Q., Gibbs, J. Raphael, Brunetti, Maura, Gronka, Susan, Wuu, Joanne, Ding, Jinhui, Mccluskey, Leo, Martinez Lage, Maria, Falcone, Dana, Hernandez, Dena G., Arepalli, Sampath, Chong, Sean, Schymick, Jennifer C., Rothstein, Jeffrey, Landi, Francesco, Wang, Yong Dong, Calvo, Andrea, Mora, Gabriele, Sabatelli, Mario, Battistini, Stefania, Salvi, Fabrizio, Spataro, Rossella, Sola, Patrizia, Borghero, Giuseppe, Giannini, Fabio, Ricci, Claudia, Moglia, Cristina, Ossola, Irene, Canosa, Antonio, Gallo, Sara, Bartolomei, Ilaria, Marinou, Kalliopi, Papetti, Laura, Conte, Amelia, Luigetti, Marco, La Bella, Vincenzo, Paladino, Piera, Caponnetto, Claudia, Volanti, Paolo, Marrosu, Maria Teresa, Murru, Maria Rita, Galassi, Giuliana, Scholz, Sonja W., Taylor, J. Paul, Restagno, Gabriella, Chiò, Adriano, Traynor, Bryan J., MONSURRO', Maria Rosaria, TEDESCHI, Gioacchino, Johnson, JO, Mandrioli, J, Benatar, M, Abramzon, Y, Van Deerlin, VM, Trojanowski, JQ, Gibbs, JR, Brunetti, M, Gronka, S, Wuu, J, Ding, J, McCluskey, L, Martinez-Lage, M, Falcone, D, Hernandez, DG, Arepalli, S, Chong, S, Schymick, JC, Rothstein, J, Landi, F, Wang, Y-D, Calvo, A, Mora, G, Sabatelli, M, Monsurrò, MR, Battistini, S, Salvi, F, Spataro, R, Sola, P, Borghero, G, Galassi, G, Scholz, SW, Taylor, JP, Restagno, G, Chiò, A, Traynor, BJ, Johnson, Janel O., Mandrioli, Jessica, Benatar, Michael, Abramzon, Yevgeniya, Van Deerlin, Vivianna M., Trojanowski, John Q., Gibbs, J. Raphael, Brunetti, Maura, Gronka, Susan, Wuu, Joanne, Ding, Jinhui, Mccluskey, Leo, Martinez Lage, Maria, Falcone, Dana, Hernandez, Dena G., Arepalli, Sampath, Chong, Sean, Schymick, Jennifer C., Rothstein, Jeffrey, Landi, Francesco, Wang, Yong Dong, Calvo, Andrea, Mora, Gabriele, Sabatelli, Mario, Monsurro', Maria Rosaria, Battistini, Stefania, Salvi, Fabrizio, Spataro, Rossella, Sola, Patrizia, Borghero, Giuseppe, Giannini, Fabio, Ricci, Claudia, Moglia, Cristina, Ossola, Irene, Canosa, Antonio, Gallo, Sara, Tedeschi, Gioacchino, Bartolomei, Ilaria, Marinou, Kalliopi, Papetti, Laura, Conte, Amelia, Luigetti, Marco, La Bella, Vincenzo, Paladino, Piera, Caponnetto, Claudia, Volanti, Paolo, Marrosu, Maria Teresa, Murru, Maria Rita, Galassi, Giuliana, Scholz, Sonja W., Taylor, J. Paul, Restagno, Gabriella, Chiò, Adriano, and Traynor, Bryan J.
Subjects: Adenosine Triphosphatase, Male, Cell Cycle Proteins, UBQLN2, Cohort Studies, 0302 clinical medicine, Reference Values, Valosin Containing Protein, Cell Cycle Protein, Reference Value, Amyotrophic lateral sclerosis, Exome sequencing, Adenosine Triphosphatases, Genetics, 0303 health sciences, General Neuroscience, Exons, Middle Aged, Pedigree, 3. Good health, Multisystem proteinopathy, Female, Settore MED/26 - Neurologia, Case-Control Studie, Chromosomes, Human, Pair 9, Human, Frontotemporal dementia, Neuroscience(all), Valosin-containing protein, Exon, Biology, Protein degradation, TARDBP, Article, 03 medical and health sciences, medicine, Humans, Aged, 030304 developmental biology, Amyotrophic lateral sclerosis, familial ALS, exome sequencing, Neuroscience (all), business.industry, Amyotrophic Lateral Sclerosis, medicine.disease, Amino Acid Substitution, Case-Control Studies, Mutation, biology.protein, Cohort Studie, business, 030217 neurology & neurosurgery, Amyotrophic Lateral Sclerosi
Abstract: Summary Using exome sequencing, we identified a p.R191Q amino acid change in the valosin-containing protein ( VCP ) gene in an Italian family with autosomal dominantly inherited amyotrophic lateral sclerosis (ALS). Mutations in VCP have previously been identified in families with Inclusion Body Myopathy, Paget disease, and Frontotemporal Dementia (IBMPFD). Screening of VCP in a cohort of 210 familial ALS cases and 78 autopsy-proven ALS cases identified four additional mutations including a p.R155H mutation in a pathologically proven case of ALS. VCP protein is essential for maturation of ubiquitin-containing autophagosomes, and mutant VCP toxicity is partially mediated through its effect on TDP-43 protein, a major constituent of ubiquitin inclusions that neuropathologically characterize ALS. Our data broaden the phenotype of IBMPFD to include motor neuron degeneration, suggest that VCP mutations may account for ∼1%–2% of familial ALS, and provide evidence directly implicating defects in the ubiquitination/protein degradation pathway in motor neuron degeneration.
Published: 2010

29. Genome-Wide Analyses Identify KIF5A as a Novel ALS Gene

Author: Nicolas, Aude, primary, Kenna, Kevin P., additional, Renton, Alan E., additional, Ticozzi, Nicola, additional, Faghri, Faraz, additional, Chia, Ruth, additional, Dominov, Janice A., additional, Kenna, Brendan J., additional, Nalls, Mike A., additional, Keagle, Pamela, additional, Rivera, Alberto M., additional, Rheenen, Wouter van, additional, Murphy, Natalie A., additional, Vugt, Joke J.F.A. van, additional, Geiger, Joshua T., additional, Van der Spek, Rick A., additional, Pliner, Hannah A., additional, Smith, Bradley N., additional, Marangi, Giuseppe, additional, Topp, Simon D., additional, Abramzon, Yevgeniya, additional, Gkazi, Athina Soragia, additional, Eicher, John D., additional, Kenna, Aoife, additional, Consortium, ITALSGEN, additional, Mora, Gabriele, additional, Calvo, Andrea, additional, Mazzini, Letizia, additional, Riva, Nilo, additional, Mandrioli, Jessica, additional, Caponnetto, Claudia, additional, Battistini, Stefania, additional, Volanti, Paolo, additional, Bella, Vincenzo La, additional, Conforti, Francesca L., additional, Borghero, Giuseppe, additional, Messina, Sonia, additional, Simone, Isabella L., additional, Trojsi, Francesca, additional, Salvi, Fabrizio, additional, Logullo, Francesco O., additional, D’Alfonso, Sandra, additional, Corrado, Lucia, additional, Capasso, Margherita, additional, Ferrucci, Luigi, additional, (GTAC) Consortium, Genomic Translation for ALS Care, additional, Martins Moreno, Cristiane de Araujo, additional, Kamalakaran, Sitharthan, additional, Goldstein, David B., additional, Consortium, The ALS Sequencing, additional, Gitler, Aaron D., additional, Harris, Tim, additional, Myers, Richard M., additional, Consortium, NYGC ALS, additional, Phatnani, Hemali, additional, Musunuri, Rajeeva Lochan, additional, Evani, Uday Shankar, additional, Abhyankar, Avinash, additional, Zody, Michael Charles, additional, Foundation, Answer ALS, additional, Kaye, Julia, additional, Finkbeiner, Steven, additional, Wyman, Stacia, additional, Lenail, Alex, additional, Lima, Leandro, additional, Fraenkel, Ernest, additional, Svendsen, Clive N., additional, Thompson, Leslie M., additional, Van Eyk, Jennifer E., additional, Berry, James D., additional, Miller, Timothy M., additional, Kolb, Stephen J., additional, Cudkowicz, Merit, additional, Baxi, Emily, additional, Development (CReATe) Consortium, Clinical Research in ALS and Relate, additional, Benatar, Michael, additional, Taylor, J. Paul, additional, Rampersaud, Evadnie, additional, Wu, Gang, additional, Wuu, Joanne, additional, Consortium, SLAGEN, additional, Lauria, Giuseppe, additional, Verde, Federico, additional, Fogh, Isabella, additional, Tiloca, Cinzia, additional, Comi, Giacomo P., additional, Sorarù, Gianni, additional, Cereda, Cristina, additional, Consortium, French ALS, additional, Corcia, Philippe, additional, Laaksovirta, Hannu, additional, Myllykangas, Liisa, additional, Jansson, Lilja, additional, Valori, Miko, additional, Ealing, John, additional, Hamdallah, Hesham, additional, Rollinson, Sara, additional, Pickering-Brown, Stuart, additional, Orrell, Richard W., additional, Sidle, Katie C., additional, Malaspina, Andrea, additional, Hardy, John, additional, Singleton, Andrew B., additional, Johnson, Janel O., additional, Arepalli, Sampath, additional, Sapp, Peter C., additional, McKenna-Yasek, Diane, additional, Polak, Meraida, additional, Asress, Seneshaw, additional, Al-Sarraj, Safa, additional, King, Andrew, additional, Troakes, Claire, additional, Vance, Caroline, additional, Belleroche, Jacqueline de, additional, Baas, Frank, additional, Asbroek, Anneloor LMA ten, additional, Muñoz-Blanco, José Luis, additional, Hernandez, Dena G., additional, Ding, Jinhui, additional, Gibbs, J. Raphael, additional, Scholz, Sonja W., additional, Floeter, Mary Kay, additional, Campbell, Roy H., additional, Landi, Francesco, additional, Pulst, Stefan M., additional, Ravits, John M., additional, MacGowan, Daniel J. L., additional, Kirby, Janine, additional, Pioro, Erik, additional, Pamphlett, Roger, additional, Broach, James, additional, Gerhard, Glenn, additional, Dunckley, Travis L., additional, Brady, Christopher B., additional, Kowall, Neil W., additional, Troncoso, Juan C., additional, Le Ber, Isabelle, additional, Mouzat, Kevin, additional, Lumbroso, Serge, additional, Heiman-Patterson, Terry D., additional, Kamel, Freya, additional, Bosch, Ludo Van Den, additional, Baloh, Robert H., additional, Strom, Tim M., additional, Meitinger, Thomas, additional, Shatunov, Aleksey, additional, Van Eijk, Kristel R., additional, de Carvalho, Mamede, additional, Kooyman, Maarten, additional, Middelkoop, Bas, additional, Moisse, Matthieu, additional, McLaughlin, Russell L., additional, Van Es, Michael A., additional, Weber, Markus, additional, Boylan, Kevin B., additional, Van Blitterswijk, Marka, additional, Rademakers, Rosa, additional, Morrison, Karen E., additional, Basak, A. Nazli, additional, Mora, Jesús S., additional, Drory, Vivian E., additional, Shaw, Pamela J., additional, Turner, Martin R., additional, Talbot, Kevin, additional, Hardiman, Orla, additional, Williams, Kelly L., additional, Fifita, Jennifer A., additional, Nicholson, Garth A., additional, Blair, Ian P., additional, Rouleau, Guy A., additional, Esteban-Pérez, Jesús, additional, García-Redondo, Alberto, additional, Al-Chalabi, Ammar, additional, Rogaeva, Ekaterina, additional, Zinman, Lorne, additional, Ostrow, Lyle, additional, Maragakis, Nicholas J., additional, Rothstein, Jeffrey D., additional, Simmons, Zachary, additional, Cooper-Knock, Johnathan, additional, Brice, Alexis, additional, Goutman, Stephen A., additional, Feldman, Eva L., additional, Gibson, Summer B., additional, Taroni, Franco, additional, Ratti, Antonia, additional, Gellera, Cinzia, additional, Van Damme, Philip, additional, Robberecht, Wim, additional, Fratta, Pietro, additional, Sabatelli, Mario, additional, Lunetta, Christian, additional, Ludolph, Albert C., additional, Andersen, Peter M., additional, Weishaupt, Jochen H., additional, Camu, William, additional, Trojanowski, John Q., additional, Van Deerlin, Vivianna M., additional, Brown, Robert H., additional, van den Berg, Leonard H., additional, Veldink, Jan H., additional, Harms, Matthew B., additional, Glass, Jonathan D., additional, Stone, David J., additional, Tienari, Pentti, additional, Silani, Vincenzo, additional, Chiò, Adriano, additional, Shaw, Christopher E., additional, Traynor, Bryan J., additional, and Landers, John E., additional
Published: 2018
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30. ATNX2 is not a regulatory gene in Italian ALS patients with C9ORF72 GGGGCC expansion

Author: Chiò, Adriano, Mora, Gabriele, Sabatelli, Mario, Caponnetto, Claudia, Lunetta, Christian, Traynor, Bryan J., Johnson, Janel O., Nalls, Mike A., Calvo, Andrea, Moglia, Cristina, Borghero, Giuseppe, Trojsi, Francesca, La Bella, Vincenzo, Volanti, Paolo, Simone, Isabella, Salvi, Fabrizio, Logullo, Francesco O., Riva, Nilo, Carrera, Paola, Giannini, Fabio, Mandrioli, Jessica, Tanel, Raffaella, Capasso, Margherita, Tremolizzo, Lucio, Battistini, Stefania, Murru, Maria Rita, Origone, Paola, Zollino, Marcella, Penco, Silvana, Mazzini, Letizia, D’Alfonso, Sandra, Restagno, Gabriella, Brunetti, Maura, Barberis, Marco, and Conforti, Francesca L.
Subjects: Male, DNA Repeat Expansion, C9orf72 Protein, Italy, Amyotrophic Lateral Sclerosis, Humans, Proteins, Female, Middle Aged, Article, Genetic Association Studies, Aged, Ataxin-2
Abstract: There are indications that both familial amyotrophic lateral sclerosis (ALS) and sporadic ALS phenotype and prognosis are partly regulated by genetic and environmental factors, supporting the theory that ALS is a multifactorial disease. The aim of this article was to assess the role of ATXN2 intermediate length repeats in a large series of Italian and Sardinian ALS patients and controls carrying a pathogenetic C9ORF72 GGGGCC hexanucleotide repeat. A total of 1972 ALS cases were identified through the database of the Italian ALS Genetic consortium, a collaborative effort including 18 ALS centers throughout Italy. The study population included: (1) 276 Italian and 57 Sardinian ALS cases who carried the C9ORF72 expansion; (2) 1340 Italian and 299 Sardinian ALS cases not carrying the C9ORF72 expansion. A total of healthy 1043 controls were also assessed. Most Italian and Sardinian cases and controls were homozygous for 22/22 or 23/23 repeats or heterozygous for 22/23 repeats of the ATXN2 gene. ATXN2 intermediate length repeats alleles (≥28) were detected in 3 (0.6%) Italian ALS cases carrying the C9ORF72 expansion, in none of the Sardinian ALS cases carrying the expansion, in 60 (4.3%) Italian cases not carrying the expansion, and in 6 (2.0%) Sardinian ALS cases without C9ORF72 expansion. Intermediate length repeat alleles were found in 12 (1.5%) Italian controls and 1 (0.84%) Sardinian controls. Therefore, ALS patients with C9ORF72 expansion showed a lower frequency of ATXN2 polyQ intermediate length repeats than both controls (Italian cases, p = 0.137; Sardinian cases, p = 0.0001) and ALS patients without C9ORF72 expansion (Italian cases, p = 0.005; Sardinian cases, p = 0.178). In our large study on Italian and Sardinian ALS patients with C9ORF72 GGGGCC hexanucleotide repeat expansion, compared to age-, gender- and ethnic-matched controls, ATXN2 polyQ intermediate length does not represent a modifier of ALS risk, differently from non-C9ORF72 mutated patients.
Published: 2015

31. CHCH10 mutations in an Italian cohort of familial and sporadic ALS patients

Author: Chiò, Adriano, Mora, Gabriele, Sabatelli, Mario, Caponnetto, Claudia, Traynor, Bryan J., Johnson, Janel O., Nalls, Mike A., Calvo, Andrea, Moglia, Cristina, Borghero, Giuseppe, Monsurrò, Maria Rosaria, La Bella, Vincenzo, Volanti, Paolo, Simone, Isabella, Salvi, Fabrizio, Logullo, Francesco O., Nilo, Riva, Battistini, Stefania, Mandrioli, Jessica, Tanel, Raffaella, Murru, Maria Rita, Mandich, Paola, Zollino, Marcella, Conforti, Francesca L., Brunetti, Maura, Barberis, Marco, Restagno, Gabriella, Penco, Silvana, and Lunetta, Christian
Subjects: Male, Amyotrophic Lateral Sclerosis, Middle Aged, Article, Cohort Studies, Mitochondrial Proteins, Italy, Frontotemporal Dementia, mental disorders, Mutation, Humans, Female, Genetic Predisposition to Disease, Genetic Association Studies, Aged
Abstract: Mutations in CHCHD10 have recently been described as a cause of frontotemporal dementia (FTD) co-morbid with amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the frequency and clinical characteristics of CHCHD10 mutations in Italian patients diagnosed with familial (n = 64) and apparently sporadic ALS (n = 224). Three apparently sporadic patients were found to carry c.100C>T (p.Pro34Ser) heterozygous variant in the exon 2 of CHCHD10. This mutation had been previously described in two unrelated French patients with FTD-ALS. However, our patients had a typical ALS, without evidence of FTD, cerebellar or extrapyramidal signs, or sensorineural deficits. We confirm that CHCHD10 mutations account for ∼1% of Italian ALS patients and are a cause of disease in subject without dementia or other atypical clinical signs.
Published: 2015

32. A Genome-Wide Association Study of Myasthenia Gravis

Author: Maestri, Michelangelo, Bartoccioni, Emanuela, Nalls, Michael A., Pasnoor, Mamatha, Sabatelli, Mario, McVey, April, Marangi, Giuseppe, Abramzon, Yevgeniya, Dimachkie, Mazen M., Kissel, John, Macek, Mark, Arepalli, Sampath, Pliner, Hannah A., Scholz, Sonja W., Chiò, Adriano, Scuderi, Flavia, Ricciardi, Roberta, Freimer, Miriam, Hernandez, Dena G., Gibbs, J. Raphael, Chaudhry, Vinay, Benatar, Michael, Errichiello, Edoardo, Provenzano, Carlo, Chong, Sean, Barohn, Richard J., Evoli, Amelia, Johnson, Janel O., Corse, Andrea, Rowin, Julie, Renton, Alan E., and Restagno, Gabriella
Subjects: immune system diseases, nervous system diseases
Abstract: Myasthenia gravis is a chronic, autoimmune, neuromuscular disease characterized by fluctuating weakness of voluntary muscle groups. Although genetic factors are known to play a role in this neuroimmunological condition, the genetic etiology underlying myasthenia gravis is not well understood.
Published: 2015
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33. A 7.5Mb duplication at chromosome 11q21-11q22.3 is associated with a novel spastic ataxia syndrome

Author: Johnson, Janel O, Stevanin, Giovanni, van de Leemput, Joyce, Hernandez, Dena G, Arepalli, Sampath, Forlani, Sylvie, Zonozi, Ryan, Gibbs, J. Raphael, Brice, Alexis, Durr, Alexandra, and Singleton, Andrew B
Subjects: Male, Genotype, Genetic Linkage, Chromosomes, Human, Pair 11, Chromosome Mapping, Trisomy, Middle Aged, Polymorphism, Single Nucleotide, Article, Pedigree, Optic Atrophy, Phenotype, Muscle Spasticity, Intellectual Disability, Humans, Spinocerebellar Ataxias, Genetic Predisposition to Disease, France
Abstract: The autosomal dominant spinocerebellar ataxias are most commonly caused by nucleotide repeat expansions followed by base-pair changes in functionally important genes. Structural variation has recently been shown to underlie spinocerebellar ataxia types 15 and 20.We applied single-nucleotide polymorphism (SNP) genotyping to determine whether structural variation causes spinocerebellar ataxia in a family from France.We identified an approximately 7.5-megabasepair duplication on chromosome 11q21-11q22.3 that segregates with disease. This duplication contains an estimated 44 genes. Duplications at this locus were not found in control individuals.We have identified a new spastic ataxia syndrome caused by a genomic duplication, which we have denoted as spinocerebellar ataxia type 39. Finding additional families with this phenotype will be important to identify the genetic lesion underlying disease.
Published: 2014

34. Association of a NovelACTA1Mutation With a Dominant Progressive Scapuloperoneal Myopathy in an Extended Family

Author: Zukosky, Kristen, primary, Meilleur, Katherine, additional, Traynor, Bryan J., additional, Dastgir, Jahannaz, additional, Medne, Livija, additional, Devoto, Marcella, additional, Collins, James, additional, Rooney, Jachinta, additional, Zou, Yaqun, additional, Yang, Michele L., additional, Gibbs, J. Raphael, additional, Meier, Markus, additional, Stetefeld, Joerg, additional, Finkel, Richard S., additional, Schessl, Joachim, additional, Elman, Lauren, additional, Felice, Kevin, additional, Ferguson, Toby A., additional, Ceyhan-Birsoy, Ozge, additional, Beggs, Alan H., additional, Tennekoon, Gihan, additional, Johnson, Janel O., additional, and Bönnemann, Carsten G., additional
Published: 2015
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35. Mutation inCPT1CAssociated With Pure Autosomal Dominant Spastic Paraplegia

Author: Rinaldi, Carlo, primary, Schmidt, Thomas, additional, Situ, Alan J., additional, Johnson, Janel O., additional, Lee, Philip R., additional, Chen, Ke-lian, additional, Bott, Laura C., additional, Fadó, Rut, additional, Harmison, George H., additional, Parodi, Sara, additional, Grunseich, Christopher, additional, Renvoisé, Benoît, additional, Biesecker, Leslie G., additional, De Michele, Giuseppe, additional, Santorelli, Filippo M., additional, Filla, Alessandro, additional, Stevanin, Giovanni, additional, Dürr, Alexandra, additional, Brice, Alexis, additional, Casals, Núria, additional, Traynor, Bryan J., additional, Blackstone, Craig, additional, Ulmer, Tobias S., additional, and Fischbeck, Kenneth H., additional
Published: 2015
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36. A 7.5-Mb duplication at chromosome 11q21-11q22.3 is associated with a novel spastic ataxia syndrome

Author: Johnson, Janel O., primary, Stevanin, Giovanni, additional, van de Leemput, Joyce, additional, Hernandez, Dena G., additional, Arepalli, Sampath, additional, Forlani, Sylvie, additional, Zonozi, Reza, additional, Gibbs, J. Raphael, additional, Brice, Alexis, additional, Durr, Alexandra, additional, and Singleton, Andrew B., additional
Published: 2014
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37. A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD

Author: Renton, Alan E., primary, Majounie, Elisa, additional, Waite, Adrian, additional, Simón-Sánchez, Javier, additional, Rollinson, Sara, additional, Gibbs, J. Raphael, additional, Schymick, Jennifer C., additional, Laaksovirta, Hannu, additional, van Swieten, John C., additional, Myllykangas, Liisa, additional, Kalimo, Hannu, additional, Paetau, Anders, additional, Abramzon, Yevgeniya, additional, Remes, Anne M., additional, Kaganovich, Alice, additional, Scholz, Sonja W., additional, Duckworth, Jamie, additional, Ding, Jinhui, additional, Harmer, Daniel W., additional, Hernandez, Dena G., additional, Johnson, Janel O., additional, Mok, Kin, additional, Ryten, Mina, additional, Trabzuni, Danyah, additional, Guerreiro, Rita J., additional, Orrell, Richard W., additional, Neal, James, additional, Murray, Alex, additional, Pearson, Justin, additional, Jansen, Iris E., additional, Sondervan, David, additional, Seelaar, Harro, additional, Blake, Derek, additional, Young, Kate, additional, Halliwell, Nicola, additional, Callister, Janis Bennion, additional, Toulson, Greg, additional, Richardson, Anna, additional, Gerhard, Alex, additional, Snowden, Julie, additional, Mann, David, additional, Neary, David, additional, Nalls, Michael A., additional, Peuralinna, Terhi, additional, Jansson, Lilja, additional, Isoviita, Veli-Matti, additional, Kaivorinne, Anna-Lotta, additional, Hölttä-Vuori, Maarit, additional, Ikonen, Elina, additional, Sulkava, Raimo, additional, Benatar, Michael, additional, Wuu, Joanne, additional, Chiò, Adriano, additional, Restagno, Gabriella, additional, Borghero, Giuseppe, additional, Sabatelli, Mario, additional, Heckerman, David, additional, Rogaeva, Ekaterina, additional, Zinman, Lorne, additional, Rothstein, Jeffrey D., additional, Sendtner, Michael, additional, Drepper, Carsten, additional, Eichler, Evan E., additional, Alkan, Can, additional, Abdullaev, Ziedulla, additional, Pack, Svetlana D., additional, Dutra, Amalia, additional, Pak, Evgenia, additional, Hardy, John, additional, Singleton, Andrew, additional, Williams, Nigel M., additional, Heutink, Peter, additional, Pickering-Brown, Stuart, additional, Morris, Huw R., additional, Tienari, Pentti J., additional, and Traynor, Bryan J., additional
Published: 2011
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38. Exome Sequencing Reveals VCP Mutations as a Cause of Familial ALS

Author: Johnson, Janel O., primary, Mandrioli, Jessica, additional, Benatar, Michael, additional, Abramzon, Yevgeniya, additional, Van Deerlin, Vivianna M., additional, Trojanowski, John Q., additional, Gibbs, J. Raphael, additional, Brunetti, Maura, additional, Gronka, Susan, additional, Wuu, Joanne, additional, Ding, Jinhui, additional, McCluskey, Leo, additional, Martinez-Lage, Maria, additional, Falcone, Dana, additional, Hernandez, Dena G., additional, Arepalli, Sampath, additional, Chong, Sean, additional, Schymick, Jennifer C., additional, Rothstein, Jeffrey, additional, Landi, Francesco, additional, Wang, Yong-Dong, additional, Calvo, Andrea, additional, Mora, Gabriele, additional, Sabatelli, Mario, additional, Monsurrò, Maria Rosaria, additional, Battistini, Stefania, additional, Salvi, Fabrizio, additional, Spataro, Rossella, additional, Sola, Patrizia, additional, Borghero, Giuseppe, additional, Galassi, Giuliana, additional, Scholz, Sonja W., additional, Taylor, J. Paul, additional, Restagno, Gabriella, additional, Chiò, Adriano, additional, and Traynor, Bryan J., additional
Published: 2011
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39. Exome Sequencing in Brown-Vialetto-Van Laere Syndrome

Author: Johnson, Janel O., primary, Gibbs, J. Raphael, additional, Van Maldergem, Lionel, additional, Houlden, Henry, additional, and Singleton, Andrew B., additional
Published: 2010
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40. A candidate gene for autoimmune myasthenia gravis.

Author: Landouré, Guida, Knight, Melanie A., Stanescu, Horia, Taye, Addis A., Yijun Shi, Diallo, Oumarou, Johnson, Janel O., Hernandez, Dena, Traynor, Bryan J., Biesecker, Leslie G., Elkahloun, Abdel, Rinaldi, Carlo, Vincent, Angela, Willcox, Nick, Kleta, Robert, Fischbeck, Kenneth H., and Burnett, Barrington G.
Published: 2012
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41. Exome sequencing in an SCA14 family demonstrates its utility in diagnosing heterogeneous diseases.

Author: Sailer A, Scholz SW, Gibbs JR, Tucci A, Johnson JO, Wood NW, Plagnol V, Hummerich H, Ding J, Hernandez D, Hardy J, Federoff HJ, Traynor BJ, Singleton AB, Houlden H, Sailer, Anna, Scholz, Sonja W, Gibbs, J Raphael, Tucci, Arianna, and Johnson, Janel O
Published: 2012
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42. Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis.

Author: Johnson, Janel O, Pioro, Erik P, Boehringer, Ashley, Chia, Ruth, Feit, Howard, Renton, Alan E, Pliner, Hannah A, Abramzon, Yevgeniya, Marangi, Giuseppe, Winborn, Brett J, Gibbs, J Raphael, Nalls, Michael A, Morgan, Sarah, Shoai, Maryam, Hardy, John, Pittman, Alan, Orrell, Richard W, Malaspina, Andrea, Sidle, Katie C, and Fratta, Pietro
Subjects: *AMYOTROPHIC lateral sclerosis, *MOTOR neurons, *RNA, *RIBOSOMAL DNA, *HUNTINGTON disease, *CENTRAL nervous system
Abstract: MATR3 is an RNA- and DNA-binding protein that interacts with TDP-43, a disease protein linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Using exome sequencing, we identified mutations in MATR3 in ALS kindreds. We also observed MATR3 pathology in ALS-affected spinal cords with and without MATR3 mutations. Our data provide more evidence supporting the role of aberrant RNA processing in motor neuron degeneration. [ABSTRACT FROM AUTHOR]
Published: 2014
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43. Exome Sequencing Identifies a Novel TRPV4 Mutation in a CMT2C Family

Author: Gaudet, Rachelle, Landouré, Guida, Sullivan, Jeremy M., Johnson, Janel O., Munns, Clare H., Shi, Yijun, Diallo, Oumarou, Ludlow, Christy L., Fischbeck, Kenneth H., Traynor, Bryan J., Burnett, Barrington G., Sumner, Charlotte J., and Gibbs, Raphael J.
Subjects: peripheral neuropathy, genetics
Abstract: Molecular and Cellular Biology
Published: 2013
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44. EXOME SEQUENCING IDENTIFIES A NOVEL TRPV4 MUTATION IN A CMT2C FAMILY.

Author: Landouré, Guida, Sullivan, Jeremy M., Johnson, Janel O., Munns, Clare H., Yijun Shi, Diallo, Oumarou, Gibbs, J. Raphael, Gaudet, Rachelle, Ludlow, Christy L., Fischbeck, Kenneth H., Traynor, Bryan J., Burnett, Barrington G., and Sumner, Charlotte J.
Published: 2012
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45. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

Author: Aude Nicolas, Kevin P. Kenna, Alan E. Renton, Nicola Ticozzi, Faraz Faghri, Ruth Chia, Janice A. Dominov, Brendan J. Kenna, Mike A. Nalls, Pamela Keagle, Alberto M. Rivera, Wouter van Rheenen, Natalie A. Murphy, Joke J.F.A. van Vugt, Joshua T. Geiger, Rick A. Van der Spek, Hannah A. Pliner, null Shankaracharya, Bradley N. Smith, Giuseppe Marangi, Simon D. Topp, Yevgeniya Abramzon, Athina Soragia Gkazi, John D. Eicher, Aoife Kenna, Gabriele Mora, Andrea Calvo, Letizia Mazzini, Nilo Riva, Jessica Mandrioli, Claudia Caponnetto, Stefania Battistini, Paolo Volanti, Vincenzo La Bella, Francesca L. Conforti, Giuseppe Borghero, Sonia Messina, Isabella L. Simone, Francesca Trojsi, Fabrizio Salvi, Francesco O. Logullo, Sandra D’Alfonso, Lucia Corrado, Margherita Capasso, Luigi Ferrucci, Cristiane de Araujo Martins Moreno, Sitharthan Kamalakaran, David B. Goldstein, Aaron D. Gitler, Tim Harris, Richard M. Myers, Hemali Phatnani, Rajeeva Lochan Musunuri, Uday Shankar Evani, Avinash Abhyankar, Michael C. Zody, Julia Kaye, Steven Finkbeiner, Stacia K. Wyman, Alex LeNail, Leandro Lima, Ernest Fraenkel, Clive N. Svendsen, Leslie M. Thompson, Jennifer E. Van Eyk, James D. Berry, Timothy M. Miller, Stephen J. Kolb, Merit Cudkowicz, Emily Baxi, Michael Benatar, J. Paul Taylor, Evadnie Rampersaud, Gang Wu, Joanne Wuu, Giuseppe Lauria, Federico Verde, Isabella Fogh, Cinzia Tiloca, Giacomo P. Comi, Gianni Sorarù, Cristina Cereda, Philippe Corcia, Hannu Laaksovirta, Liisa Myllykangas, Lilja Jansson, Miko Valori, John Ealing, Hisham Hamdalla, Sara Rollinson, Stuart Pickering-Brown, Richard W. Orrell, Katie C. Sidle, Andrea Malaspina, John Hardy, Andrew B. Singleton, Janel O. Johnson, Sampath Arepalli, Peter C. Sapp, Diane McKenna-Yasek, Meraida Polak, Seneshaw Asress, Safa Al-Sarraj, Andrew King, Claire Troakes, Caroline Vance, Jacqueline de Belleroche, Frank Baas, Anneloor L.M.A. ten Asbroek, José Luis Muñoz-Blanco, Dena G. Hernandez, Jinhui Ding, J. Raphael Gibbs, Sonja W. Scholz, Mary Kay Floeter, Roy H. Campbell, Francesco Landi, Robert Bowser, Stefan M. Pulst, John M. Ravits, Daniel J.L. MacGowan, Janine Kirby, Erik P. Pioro, Roger Pamphlett, James Broach, Glenn Gerhard, Travis L. Dunckley, Christopher B. Brady, Neil W. Kowall, Juan C. Troncoso, Isabelle Le Ber, Kevin Mouzat, Serge Lumbroso, Terry D. Heiman-Patterson, Freya Kamel, Ludo Van Den Bosch, Robert H. Baloh, Tim M. Strom, Thomas Meitinger, Aleksey Shatunov, Kristel R. Van Eijk, Mamede de Carvalho, Maarten Kooyman, Bas Middelkoop, Matthieu Moisse, Russell L. McLaughlin, Michael A. Van Es, Markus Weber, Kevin B. Boylan, Marka Van Blitterswijk, Rosa Rademakers, Karen E. Morrison, A. Nazli Basak, Jesús S. Mora, Vivian E. Drory, Pamela J. Shaw, Martin R. Turner, Kevin Talbot, Orla Hardiman, Kelly L. Williams, Jennifer A. Fifita, Garth A. Nicholson, Ian P. Blair, Guy A. Rouleau, Jesús Esteban-Pérez, Alberto García-Redondo, Ammar Al-Chalabi, Ekaterina Rogaeva, Lorne Zinman, Lyle W. Ostrow, Nicholas J. Maragakis, Jeffrey D. Rothstein, Zachary Simmons, Johnathan Cooper-Knock, Alexis Brice, Stephen A. Goutman, Eva L. Feldman, Summer B. Gibson, Franco Taroni, Antonia Ratti, Cinzia Gellera, Philip Van Damme, Wim Robberecht, Pietro Fratta, Mario Sabatelli, Christian Lunetta, Albert C. Ludolph, Peter M. Andersen, Jochen H. Weishaupt, William Camu, John Q. Trojanowski, Vivianna M. Van Deerlin, Robert H. Brown, Leonard H. van den Berg, Jan H. Veldink, Matthew B. Harms, Jonathan D. Glass, David J. Stone, Pentti Tienari, Vincenzo Silani, Adriano Chiò, Christopher E. Shaw, Bryan J. Traynor, John E. Landers, Isabella Simone, Giancarlo Logroscino, Ilaria Bartolomei, Maria Rita Murru, Emanuela Costantino, Carla Pani, Roberta Puddu, Carla Caredda, Valeria Piras, Stefania Tranquilli, Stefania Cuccu, Daniela Corongiu, Maurizio Melis, Antonio Milia, Francesco Marrosu, Maria Giovanna Marrosu, Gianluca Floris, Antonino Cannas, Gianluigi Mancardi, Paola Origone, Paola Mandich, Sebastiano Cavallaro, Kalliopi Marinou, Riccardo Sideri, Silvana Penco, Lorena Mosca, Giuseppe Lauria Pinter, Massimo Corbo, Paola Carrera, Nicola Fini, Antonio Fasano, Lucio Tremolizzo, Alessandro Arosio, Carlo Ferrarese, Gioacchino Tedeschi, Maria Rosaria Monsurrò, Giovanni Piccirillo, Cinzia Femiano, Anna Ticca, Enzo Ortu, Rossella Spataro, Tiziana Colletti, Marcella Zollino, Amelia Conte, Marco Luigetti, Serena Lattante, Marialuisa Santarelli, Antonio Petrucci, Maura Pugliatti, Angelo Pirisi, Leslie D. Parish, Patrizia Occhineri, Fabio Giannini, Claudia Ricci, Michele Benigni, Tea B. Cau, Daniela Loi, Cristina Moglia, Maura Brunetti, Marco Barberis, Gabriella Restagno, Federico Casale, Giuseppe Marrali, Giuseppe Fuda, Irene Ossola, Stefania Cammarosano, Antonio Canosa, Antonio Ilardi, Umberto Manera, Maurizio Grassano, Raffaella Tanel, Fabrizio Pisano, Neil A. Shneider, Stephen Goutman, Siddharthan Chandran, Suvankar Pal, George Manousakis, Stanley H. Appel, Ericka Simpson, Leo Wang, Summer Gibson, Richard Bedlack, David Lacomis, Dhruv Sareen, Alexander Sherman, Lucie Bruijn, Michelle Penny, Andrew S. Allen, Stanley Appel, Richard S. Bedlack, Braden E. Boone, Robert Brown, John P. Carulli, Alessandra Chesi, Wendy K. Chung, Elizabeth T. Cirulli, Gregory M. Cooper, Julien Couthouis, Aaron G. Day-Williams, Patrick A. Dion, Yujun Han, Sebastian D. Hayes, Angela L. Jones, Jonathan Keebler, Brian J. Krueger, Brittany N. Lasseigne, Shawn E. Levy, Yi-Fan Lu, Tom Maniatis, Slavé Petrovski, Alya R. Raphael, Zhong Ren, Katherine B. Sims, John F. Staropoli, Lindsay L. Waite, Quanli Wang, Jack R. Wimbish, Winnie W. Xin, Justin Kwan, James R. Broach, Ximena Arcila-Londono, Edward B. Lee, Noah Zaitlen, Gregory A. Cox, Steve Finkbeiner, Efthimios Dardiotis, Eran Hornstein, Daniel J. MacGowan, Terry Heiman-Patterson, Molly G. Hammell, Nikolaos A. Patsopoulos, Joshua Dubnau, Avindra Nath, Stacia Wyman, Alexander LeNail, Jenny Van Eyk, Stephan Züchner, Rebecca Schule, Jacob McCauley, Sumaira Hussain, Anne Cooley, Marielle Wallace, Christine Clayman, Richard Barohn, Jeffrey Statland, John Ravits, Andrea Swenson, Carlayne Jackson, Jaya Trivedi, Shaida Khan, Jonathan Katz, Liberty Jenkins, Ted Burns, Kelly Gwathmey, James Caress, Corey McMillan, Lauren Elman, Erik Pioro, Jeannine Heckmann, Yuen So, David Walk, Samuel Maiser, Jinghui Zhang, Fabiola De Marchi, Stefania Corti, Mauro Ceroni, Gabriele Siciliano, Massimiliano Filosto, Maurizio Inghilleri, Silvia Peverelli, Claudia Colombrita, Barbara Poletti, Luca Maderna, Roberto Del Bo, Stella Gagliardi, Giorgia Querin, Cinzia Bertolin, Viviana Pensato, Barbara Castellotti, Vincent Meininger, Gérard Besson, Emmeline Lagrange, Pierre Clavelou, Nathalie Guy, Philippe Couratier, Patrick Vourch, Véronique Danel, Emilien Bernard, Gwendal Lemasson, Ahmad Al Kheifat, Peter Andersen, Adriano Chio, Jonathan Cooper-Knock, Annelot Dekker, Vivian Drory, Alberto Garcia Redondo, Marc Gotkine, Winston Hide, Alfredo Iacoangeli, Jonathan Glass, Kevin Kenna, Matthew Kiernan, John Landers, Russell McLaughlin, Jonathan Mill, Miguel Mitne Neto, Mattieu Moisse, Jesus Mora Pardina, Karen Morrison, Stephen Newhouse, Susana Pinto, Sara Pulit, Pamela Shaw, Chris Shaw, William Sproviero, Gijs Tazelaar, Philip van Damme, Leonard van den Berg, Rick van der Spek, Kristel van Eijk, Michael van Es, Joke van Vugt, Jan Veldink, Mayana Zatz, Denis C. Bauer, Natalie A. Twine, Department of Neurosciences, Pentti Tienari / Principal Investigator, Neurologian yksikkö, Research Programs Unit, Clinicum, Research Programme for Molecular Neurology, University of Helsinki, Medicum, Department of Pathology, HUS Neurocenter, Nicolas A., Kenna K.P., Renton A.E., Ticozzi N., Faghri F., Chia R., Dominov J.A., Kenna B.J., Nalls M.A., Keagle P., Rivera A.M., van Rheenen W., Murphy N.A., van Vugt J.J.F.A., Geiger J.T., Van der Spek R.A., Pliner H.A., Shankaracharya, Smith B.N., Marangi G., Topp S.D., Abramzon Y., Gkazi A.S., Eicher J.D., Kenna A., Logullo F.O., Simone I.L., Logroscino G., Salvi F., Bartolomei I., Borghero G., Murru M.R., Costantino E., Pani C., Puddu R., Caredda C., Piras V., Tranquilli S., Cuccu S., Corongiu D., Melis M., Milia A., Marrosu F., Marrosu M.G., Floris G., Cannas A., Capasso M., Caponnetto C., Mancardi G., Origone P., Mandich P., Conforti F.L., Cavallaro S., Mora G., Marinou K., Sideri R., Penco S., Mosca L., Lunetta C., Pinter G.L., Corbo M., Riva N., Carrera P., Volanti P., Mandrioli J., Fini N., Fasano A., Tremolizzo L., Arosio A., Ferrarese C., Trojsi F., Tedeschi G., Monsurro M.R., Piccirillo G., Femiano C., Ticca A., Ortu E., La Bella V., Spataro R., Colletti T., Sabatelli M., Zollino M., Conte A., Luigetti M., Lattante S., Santarelli M., Petrucci A., Pugliatti M., Pirisi A., Parish L.D., Occhineri P., Giannini F., Battistini S., Ricci C., Benigni M., Cau T.B., Loi D., Calvo A., Moglia C., Brunetti M., Barberis M., Restagno G., Casale F., Marrali G., Fuda G., Ossola I., Cammarosano S., Canosa A., Ilardi A., Manera U., Grassano M., Tanel R., Pisano F., Mazzini L., Messina S., D'Alfonso S., Corrado L., Ferrucci L., Harms M.B., Goldstein D.B., Shneider N.A., Goutman S.A., Simmons Z., Miller T.M., Chandran S., Pal S., Manousakis G., Appel S.H., Simpson E., Wang L., Baloh R.H., Gibson S.B., Bedlack R., Lacomis D., Sareen D., Sherman A., Bruijn L., Penny M., Moreno C.D.A.M., Kamalakaran S., Allen A.S., Boone B.E., Brown R.H., Carulli J.P., Chesi A., Chung W.K., Cirulli E.T., Cooper G.M., Couthouis J., Day-Williams A.G., Dion P.A., Gitler A.D., Glass J.D., Han Y., Harris T., Hayes S.D., Jones A.L., Keebler J., Krueger B.J., Lasseigne B.N., Levy S.E., Lu Y.-F., Maniatis T., McKenna-Yasek D., Myers R.M., Petrovski S., Pulst S.M., Raphael A.R., Ravits J.M., Ren Z., Rouleau G.A., Sapp P.C., Sims K.B., Staropoli J.F., Waite L.L., Wang Q., Wimbish J.R., Xin W.W., Phatnani H., Kwan J., Broach J., Arcila-Londono X., Lee E.B., Van Deerlin V.M., Fraenkel E., Ostrow L.W., Baas F., Zaitlen N., Berry J.D., Malaspina A., Fratta P., Cox G.A., Thompson L.M., Finkbeiner S., Dardiotis E., Hornstein E., MacGowan D.J.L., Heiman-Patterson T., Hammell M.G., Patsopoulos N.A., Dubnau J., Nath A., Musunuri R.L., Evani U.S., Abhyankar A., Zody M.C., Kaye J., Wyman S.K., LeNail A., Lima L., Rothstein J.D., Svendsen C.N., Van Eyk J.E., Maragakis N.J., Kolb S.J., Cudkowicz M., Baxi E., Benatar M., Taylor J.P., Wu G., Rampersaud E., Wuu J., Rademakers R., Zuchner S., Schule R., McCauley J., Hussain S., Cooley A., Wallace M., Clayman C., Barohn R., Statland J., Swenson A., Jackson C., Trivedi J., Khan S., Katz J., Jenkins L., Burns T., Gwathmey K., Caress J., McMillan C., Elman L., Pioro E.P., Heckmann J., So Y., Walk D., Maiser S., Zhang J., Silani V., Gellera C., Ratti A., Taroni F., Lauria G., Verde F., Fogh I., Tiloca C., Comi G.P., Soraru G., Cereda C., De Marchi F., Corti S., Ceroni M., Siciliano G., Filosto M., Inghilleri M., Peverelli S., Colombrita C., Poletti B., Maderna L., Del Bo R., Gagliardi S., Querin G., Bertolin C., Pensato V., Castellotti B., Camu W., Mouzat K., Lumbroso S., Corcia P., Meininger V., Besson G., Lagrange E., Clavelou P., Guy N., Couratier P., Vourch P., Danel V., Bernard E., Lemasson G., Laaksovirta H., Myllykangas L., Jansson L., Valori M., Ealing J., Hamdalla H., Rollinson S., Pickering-Brown S., Orrell R.W., Sidle K.C., Hardy J., Singleton A.B., Johnson J.O., Arepalli S., Polak M., Asress S., Al-Sarraj S., King A., Troakes C., Vance C., de Belleroche J., ten Asbroek A.L.M.A., Munoz-Blanco J.L., Hernandez D.G., Ding J., Gibbs J.R., Scholz S.W., Floeter M.K., Campbell R.H., Landi F., Bowser R., Kirby J., Pamphlett R., Gerhard G., Dunckley T.L., Brady C.B., Kowall N.W., Troncoso J.C., Le Ber I., Heiman-Patterson T.D., Kamel F., Van Den Bosch L., Strom T.M., Meitinger T., Shatunov A., Van Eijk K.R., de Carvalho M., Kooyman M., Middelkoop B., Moisse M., McLaughlin R.L., Van Es M.A., Weber M., Boylan K.B., Van Blitterswijk M., Morrison K.E., Basak A.N., Mora J.S., Drory V.E., Shaw P.J., Turner M.R., Talbot K., Hardiman O., Williams K.L., Fifita J.A., Nicholson G.A., Blair I.P., Esteban-Perez J., Garcia-Redondo A., Al-Chalabi A., Al Kheifat A., Andersen P.M., Chio A., Cooper-Knock J., Dekker A., Redondo A.G., Gotkine M., Hide W., Iacoangeli A., Kiernan M., Landers J.E., Mill J., Neto M.M., Pardina J.M., Newhouse S., Pinto S., Pulit S., Robberecht W., Shaw C., Sproviero W., Tazelaar G., Van Damme P., van den Berg L.H., van Vugt J., Veldink J.H., Zatz M., Bauer D.C., Twine N.A., Rogaeva E., Zinman L., Brice A., Feldman E.L., Ludolph A.C., Weishaupt J.H., Trojanowski J.Q., Stone D.J., Tienari P., Shaw C.E., Traynor B.J., ITALSGEN Consortium, Genomic Translation ALS Care GTAC, ALS Sequencing Consortium, NYGC ALS Consortium, Answer ALS Fdn, Clinical Res ALS Related Disorders, SLAGEN Consortium, French ALS Consortium, Project MinE ALS Sequencing Consor, Medical Research Council (MRC), ANS - Complex Trait Genetics, Human Genetics, ARD - Amsterdam Reproduction and Development, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Università cattolica del Sacro Cuore [Roma] (Unicatt), Centre référent Sclérose Latérale Amyotrophique [CHRU Montpellier] (SLA CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1), Lunar and Planetary Laboratory [Tucson] (LPL), University of Arizona, Università degli studi di Torino (UNITO), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), New York Genome Center [New York], New York Genome Center, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), St Jude Children's Research Hospital, Howard Hughes Medical Institute [Chevy Chase] (HHMI), Howard Hughes Medical Institute (HHMI), Centre de compétence de la Sclérose Latérale Amyotrophique [CHRU Tours] (SLA CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), University College of London [London] (UCL), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), King‘s College London, University of New Haven [Connecticut], Princeton University, Laboratoire de Biochimie [CHRU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Helmholtz-Zentrum München (HZM), University Medical Center [Utrecht], Deutsches Forschungszentrum für Künstliche Intelligenz GmbH = German Research Center for Artificial Intelligence (DFKI), Mayo Clinic [Jacksonville], Trinity College Dublin, Maurice Wohl Clinical Neuroscience Institut, Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Repositório da Universidade de Lisboa, Nicolas, A, Kenna, K, Renton, A, Ticozzi, N, Faghri, F, Chia, R, Dominov, J, Kenna, B, Nalls, M, Keagle, P, Rivera, A, van Rheenen, W, Murphy, N, van Vugt, J, Geiger, J, van der Spek, R, Pliner, H, Shankaracharya, N, Smith, B, Marangi, G, Topp, S, Abramzon, Y, Gkazi, A, Eicher, J, Kenna, A, Logullo, F, Simone, I, Logroscino, G, Salvi, F, Bartolomei, I, Borghero, G, Murru, M, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M, Floris, G, Cannas, A, Capasso, M, Caponnetto, C, Mancardi, G, Origone, P, Mandich, P, Conforti, F, Cavallaro, S, Mora, G, Marinou, K, Sideri, R, Penco, S, Mosca, L, Lunetta, C, Pinter, G, Corbo, M, Riva, N, Carrera, P, Volanti, P, Mandrioli, J, Fini, N, Fasano, A, Tremolizzo, L, Arosio, A, Ferrarese, C, Trojsi, F, Tedeschi, G, Monsurrò, M, Piccirillo, G, Femiano, C, Ticca, A, Ortu, E, La Bella, V, Spataro, R, Colletti, T, Sabatelli, M, Zollino, M, Conte, A, Luigetti, M, Lattante, S, Santarelli, M, Petrucci, A, Pugliatti, M, Pirisi, A, Parish, L, Occhineri, P, Giannini, F, Battistini, S, Ricci, C, Benigni, M, Cau, T, Loi, D, Calvo, A, Moglia, C, Brunetti, M, Barberis, M, Restagno, G, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Canosa, A, Ilardi, A, Manera, U, Grassano, M, Tanel, R, Pisano, F, Mazzini, L, Messina, S, D'Alfonso, S, Corrado, L, Ferrucci, L, Harms, M, Goldstein, D, Shneider, N, Goutman, S, Simmons, Z, Miller, T, Chandran, S, Pal, S, Manousakis, G, Appel, S, Simpson, E, Wang, L, Baloh, R, Gibson, S, Bedlack, R, Lacomis, D, Sareen, D, Sherman, A, Bruijn, L, Penny, M, Moreno, C, Kamalakaran, S, Allen, A, Boone, B, Brown, R, Carulli, J, Chesi, A, Chung, W, Cirulli, E, Cooper, G, Couthouis, J, Day-Williams, A, Dion, P, Gitler, A, Glass, J, Han, Y, Harris, T, Hayes, S, Jones, A, Keebler, J, Krueger, B, Lasseigne, B, Levy, S, Lu, Y, Maniatis, T, McKenna-Yasek, D, Myers, R, Petrovski, S, Pulst, S, Raphael, A, Ravits, J, Ren, Z, Rouleau, G, Sapp, P, Sims, K, Staropoli, J, Waite, L, Wang, Q, Wimbish, J, Xin, W, Phatnani, H, Kwan, J, Broach, J, Arcila-Londono, X, Lee, E, Van Deerlin, V, Fraenkel, E, Ostrow, L, Baas, F, Zaitlen, N, Berry, J, Malaspina, A, Fratta, P, Cox, G, Thompson, L, Finkbeiner, S, Dardiotis, E, Hornstein, E, Macgowan, D, Heiman-Patterson, T, Hammell, M, Patsopoulos, N, Dubnau, J, Nath, A, Musunuri, R, Evani, U, Abhyankar, A, Zody, M, Kaye, J, Wyman, S, Lenail, A, Lima, L, Rothstein, J, Svendsen, C, Van Eyk, J, Maragakis, N, Kolb, S, Cudkowicz, M, Baxi, E, Benatar, M, Taylor, J, Wu, G, Rampersaud, E, Wuu, J, Rademakers, R, Züchner, S, Schule, R, Mccauley, J, Hussain, S, Cooley, A, Wallace, M, Clayman, C, Barohn, R, Statland, J, Swenson, A, Jackson, C, Trivedi, J, Khan, S, Katz, J, Jenkins, L, Burns, T, Gwathmey, K, Caress, J, Mcmillan, C, Elman, L, Pioro, E, Heckmann, J, So, Y, Walk, D, Maiser, S, Zhang, J, Silani, V, Gellera, C, Ratti, A, Taroni, F, Lauria, G, Verde, F, Fogh, I, Tiloca, C, Comi, G, Sorarù, G, Cereda, C, De Marchi, F, Corti, S, Ceroni, M, Siciliano, G, Filosto, M, Inghilleri, M, Peverelli, S, Colombrita, C, Poletti, B, Maderna, L, Del Bo, R, Gagliardi, S, Querin, G, Bertolin, C, Pensato, V, Castellotti, B, Camu, W, Mouzat, K, Lumbroso, S, Corcia, P, Meininger, V, Besson, G, Lagrange, E, Clavelou, P, Guy, N, Couratier, P, Vourch, P, Danel, V, Bernard, E, Lemasson, G, Laaksovirta, H, Myllykangas, L, Jansson, L, Valori, M, Ealing, J, Hamdalla, H, Rollinson, S, Pickering-Brown, S, Orrell, R, Sidle, K, Hardy, J, Singleton, A, Johnson, J, Arepalli, S, Polak, M, Asress, S, Al-Sarraj, S, King, A, Troakes, C, Vance, C, de Belleroche, J, ten Asbroek, A, Muñoz-Blanco, J, Hernandez, D, Ding, J, Gibbs, J, Scholz, S, Floeter, M, Campbell, R, Landi, F, Bowser, R, Kirby, J, Pamphlett, R, Gerhard, G, Dunckley, T, Brady, C, Kowall, N, Troncoso, J, Le Ber, I, Kamel, F, Van Den Bosch, L, Strom, T, Meitinger, T, Shatunov, A, Van Eijk, K, de Carvalho, M, Kooyman, M, Middelkoop, B, Moisse, M, Mclaughlin, R, Van Es, M, Weber, M, Boylan, K, Van Blitterswijk, M, Morrison, K, Basak, A, Mora, J, Drory, V, Shaw, P, Turner, M, Talbot, K, Hardiman, O, Williams, K, Fifita, J, Nicholson, G, Blair, I, Esteban-Pérez, J, García-Redondo, A, Al-Chalabi, A, Al Kheifat, A, Andersen, P, Chio, A, Cooper-Knock, J, Dekker, A, Redondo, A, Gotkine, M, Hide, W, Iacoangeli, A, Kiernan, M, Landers, J, Mill, J, Neto, M, Pardina, J, Newhouse, S, Pinto, S, Pulit, S, Robberecht, W, Shaw, C, Sproviero, W, Tazelaar, G, van Damme, P, van den Berg, L, van Eijk, K, van Es, M, Veldink, J, Zatz, M, Bauer, D, Twine, N, Rogaeva, E, Zinman, L, Brice, A, Feldman, E, Ludolph, A, Weishaupt, J, Trojanowski, J, Stone, D, Tienari, P, Chiò, A, Traynor, B, Nicolas, Aude, Kenna, Kevin P, Renton, Alan E, Ticozzi, Nicola, Faghri, Faraz, Chia, Ruth, Dominov, Janice A, Kenna, Brendan J, Nalls, Mike A, Keagle, Pamela, Rivera, Alberto M, van Rheenen, Wouter, Murphy, Natalie A, van Vugt, Joke J F A, Geiger, Joshua T, Van der Spek, Rick A, Pliner, Hannah A, Shankaracharya, Null, Smith, Bradley N, Marangi, Giuseppe, Topp, Simon D, Abramzon, Yevgeniya, Gkazi, Athina Soragia, Eicher, John D, Kenna, Aoife, Mora, Gabriele, Calvo, Andrea, Mazzini, Letizia, Riva, Nilo, Mandrioli, Jessica, Caponnetto, Claudia, Battistini, Stefania, Volanti, Paolo, La Bella, Vincenzo, Conforti, Francesca L, Borghero, Giuseppe, Messina, Sonia, Simone, Isabella L, Trojsi, Francesca, Salvi, Fabrizio, Logullo, Francesco O, D'Alfonso, Sandra, Corrado, Lucia, Capasso, Margherita, Ferrucci, Luigi, Logullo, Fo, Murru, Mr, Marrosu, Mg, Conforti, Fl, Pinter, Gl, Tedeschi, Gioacchino, Monsurrò, Maria Rosaria, Parish, Ld, Cau, Tb, Moreno, Cristiane de Araujo Martin, Kamalakaran, Sitharthan, Goldstein, David B, Gitler, Aaron D, Harris, Tim, Myers, Richard M, Phatnani, Hemali, Musunuri, Rajeeva Lochan, Evani, Uday Shankar, Abhyankar, Avinash, Zody, Michael C, Kaye, Julia, Finkbeiner, Steven, Wyman, Stacia K, Lenail, Alex, Lima, Leandro, Fraenkel, Ernest, Svendsen, Clive N, Thompson, Leslie M, Van Eyk, Jennifer E, Berry, James D, Miller, Timothy M, Kolb, Stephen J, Cudkowicz, Merit, Baxi, Emily, Benatar, Michael, Taylor, J Paul, Rampersaud, Evadnie, Wu, Gang, Wuu, Joanne, Lauria, Giuseppe, Verde, Federico, Fogh, Isabella, Tiloca, Cinzia, Comi, Giacomo P, Sorarù, Gianni, Cereda, Cristina, Corcia, Philippe, Laaksovirta, Hannu, Myllykangas, Liisa, Jansson, Lilja, Valori, Miko, Ealing, John, Hamdalla, Hisham, Rollinson, Sara, Pickering-Brown, Stuart, Orrell, Richard W, Sidle, Katie C, Malaspina, Andrea, Hardy, John, Singleton, Andrew B, Johnson, Janel O, Arepalli, Sampath, Sapp, Peter C, McKenna-Yasek, Diane, Polak, Meraida, Asress, Seneshaw, Al-Sarraj, Safa, King, Andrew, Troakes, Claire, Vance, Caroline, de Belleroche, Jacqueline, Baas, Frank, Ten Asbroek, Anneloor L M A, Muñoz-Blanco, José Lui, Hernandez, Dena G, Ding, Jinhui, Gibbs, J Raphael, Scholz, Sonja W, Floeter, Mary Kay, Campbell, Roy H, Landi, Francesco, Bowser, Robert, Pulst, Stefan M, Ravits, John M, Macgowan, Daniel J L, Kirby, Janine, Pioro, Erik P, Pamphlett, Roger, Broach, Jame, Gerhard, Glenn, Dunckley, Travis L, Brady, Christopher B, Kowall, Neil W, Troncoso, Juan C, Le Ber, Isabelle, Mouzat, Kevin, Lumbroso, Serge, Heiman-Patterson, Terry D, Kamel, Freya, Van Den Bosch, Ludo, Baloh, Robert H, Strom, Tim M, Meitinger, Thoma, Shatunov, Aleksey, Van Eijk, Kristel R, de Carvalho, Mamede, Kooyman, Maarten, Middelkoop, Ba, Moisse, Matthieu, Mclaughlin, Russell L, Van Es, Michael A, Weber, Marku, Boylan, Kevin B, Van Blitterswijk, Marka, Rademakers, Rosa, Morrison, Karen E, Basak, A Nazli, Mora, Jesús S, Drory, Vivian E, Shaw, Pamela J, Turner, Martin R, Talbot, Kevin, Hardiman, Orla, Williams, Kelly L, Fifita, Jennifer A, Nicholson, Garth A, Blair, Ian P, Rouleau, Guy A, Esteban-Pérez, Jesú, García-Redondo, Alberto, Al-Chalabi, Ammar, Rogaeva, Ekaterina, Zinman, Lorne, Ostrow, Lyle W, Maragakis, Nicholas J, Rothstein, Jeffrey D, Simmons, Zachary, Cooper-Knock, Johnathan, Brice, Alexi, Goutman, Stephen A, Feldman, Eva L, Gibson, Summer B, Taroni, Franco, Ratti, Antonia, Gellera, Cinzia, Van Damme, Philip, Robberecht, Wim, Fratta, Pietro, Sabatelli, Mario, Lunetta, Christian, Ludolph, Albert C, Andersen, Peter M, Weishaupt, Jochen H, Camu, William, Trojanowski, John Q, Van Deerlin, Vivianna M, Brown, Robert H, van den Berg, Leonard H, Veldink, Jan H, Harms, Matthew B, Glass, Jonathan D, Stone, David J, Tienari, Pentti, Silani, Vincenzo, Chiò, Adriano, Shaw, Christopher E, Traynor, Bryan J, Landers, John E, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Male, Als gene, Genome-wide association study, FAMILIAL ALS, ALS, axonal transport, cargo, GWAS, KIF5A, WES, WGS, 0302 clinical medicine, 80 and over, Psychology, Aetiology, Aged, 80 and over, 0303 health sciences, French ALS Consortium, Kinesin, KINESIN HEAVY-CHAIN, Cognitive Sciences, Human, Hereditary spastic paraplegia, Neuroscience(all), Single-nucleotide polymorphism, TARGETED DISRUPTION, Article, 03 medical and health sciences, Genetics, Humans, Amino Acid Sequence, Loss function, Aged, HEXANUCLEOTIDE REPEAT, Neuroscience (all), MUTATIONS, Amyotrophic Lateral Sclerosis, 3112 Neurosciences, 1702 Cognitive Science, medicine.disease, ITALSGEN Consortium, Answer ALS Foundation, 030104 developmental biology, ALS Sequencing Consortium, Human medicine, 1109 Neurosciences, 030217 neurology & neurosurgery, 0301 basic medicine, [SDV]Life Sciences [q-bio], Kinesins, Neurodegenerative, Genetic analysis, Genome, AMYOTROPHIC-LATERAL-SCLEROSIS, 3124 Neurology and psychiatry, Cohort Studies, Pathogenesis, Loss of Function Mutation, Missense mutation, 2.1 Biological and endogenous factors, Amyotrophic lateral sclerosis, NYGC ALS Consortium, General Neuroscience, ALS, axonal transport, cargo, GWAS, KIF5A, WES, WGS, Middle Aged, Phenotype, Settore MED/26 - NEUROLOGIA, Neurological, Project MinE ALS Sequencing Consortium, Female, Adult, Biology, GENOTYPE IMPUTATION, Genome-Wide Association Study, Young Adult, NO, Rare Diseases, medicine, SLAGEN Consortium, Gene, 030304 developmental biology, Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium, Neurology & Neurosurgery, Human Genome, Neurosciences, AXONAL-TRANSPORT, Brain Disorders, Family member, DNA-DAMAGE, MOTOR-NEURONS, 3111 Biomedicine, Cohort Studie, Genomic Translation for ALS Care (GTAC) Consortium, Amyotrophic Lateral Sclerosi
Abstract: © 2018 Elsevier Inc., To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
Published: 2018

46. ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion

Author: Chiò, A, Mora, G, Sabatelli, M, Caponnetto, C, Lunetta, C, Traynor, B. J, Johnson, J. O, Nalls, M. A, Calvo, A, Moglia, C, Borghero, G, Trojsi, F, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F. O, Riva, N, Carrera, P, Giannini, F, Mandrioli, J, Tanel, R, Capasso, M, Tremolizzo, L, Battistini, S, Murru, M. R, Origone, P, Zollino, M, Penco, S, Mazzini, L, D'Alfonso, S, Restagno, G, Brunetti, M, Barberis, M, Conforti, F. L, Logroscino, G, Bartolomei, I, Mancardi, G, Mandich, P, Marinou, K, Sideri, R, Mosca, L, Lauria Pinter, G, Corbo, M, Fini, N, Fasano, A, Arosio, A, Ferrarese, C, Tedeschi, G, Monsurrò, M. R, Piccirillo, G, Femiano, C, Bersano, A, Corrado, L, Bagarotti, A, Spataro, R, Colletti, T, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Ricci, C, Benigni, M, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Manera, U, Bertuzzo, D, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M. G, Floris, G, Cannas, A, Ticca, A, Pugliatti, M, Pirisi, A, Parish, L. D, Occhineri, P, Ortu, E, Cau, T. B, Loi, D, Chiò, A., Mora, G., Sabatelli, M., Caponnetto, C., Lunetta, C., Traynor, B., Johnson, J., Nalls, M., Calvo, A., Moglia, C., Borghero, G., Trojsi, F., LA BELLA, V., Volanti, P., Simone, I., Salvi, F., Logullo, F., Riva, N., Carrera, P., Giannini, F., Mandrioli, J., Tanel, R., Capasso, M., Tremolizzo, L., Battistini, S., Murru, M., Origone, P., Zollino, M., Penco, S., Mazzini, L., D'Alfonso, S., Restagno, G., Brunetti, M., Barberis, M., Conforti, F., Chiò, Adriano, Mora, Gabriele, Sabatelli, Mario, Caponnetto, Claudia, Lunetta, Christian, Traynor, Bryan J, Johnson, Janel O, Nalls, Mike A, Calvo, Andrea, Moglia, Cristina, Borghero, Giuseppe, Trojsi, Francesca, La Bella, Vincenzo, Volanti, Paolo, Simone, Isabella, Salvi, Fabrizio, Logullo, Francesco O, Riva, Nilo, Carrera, Paola, Giannini, Fabio, Mandrioli, Jessica, Tanel, Raffaella, Capasso, Margherita, Tremolizzo, Lucio, Battistini, Stefania, Murru, Maria Rita, Origone, Paola, Zollino, Marcella, Penco, Silvana, Logroscino, G, Bartolomei, I, Mancardi, G, Mandich, P, Marinou, K, Sideri, R, Mosca, L, Pinter, Gl, Corbo, M, Fini, N, Fasano, A, Arosio, A, Ferrarese, C, Tedeschi, Gioacchino, Monsurro', Maria Rosaria, Piccirillo, G, Femiano, C, Bersano, A, Corrado, L, Bagarotti, A, Spataro, R, Colletti, T, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Ricci, C, Benigni, M, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Manera, U, Bertuzzo, D, Tanel, R, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, Mg, Floris, G, Cannas, A, Ticca, A, Pugliatti, M, Pirisi, A, Parish, Ld, Occhineri, P, Ortu, E, Cau, Tb, Loi, D, Mazzini, Letizia, D'Alfonso, Sandra, Restagno, Gabriella, Brunetti, Maura, Barberis, Marco, Conforti, Francesca L., Chiò, A, Mora, G, Sabatelli, M, Caponnetto, C, Lunetta, C, Traynor, B, Johnson, J, Nalls, M, Calvo, A, Moglia, C, Borghero, G, Trojsi, F, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F, Riva, N, Carrera, P, Giannini, F, Mandrioli, J, Capasso, M, Tremolizzo, L, Battistini, S, Murru, M, Origone, P, Zollino, M, Penco, S, Mazzini, L, D'Alfonso, S, Restagno, G, Brunetti, M, Barberis, M, Conforti, F, Lauria Pinter, G, Tedeschi, G, Monsurrò, M, Marrosu, M, Parish, L, and Cau, T
Subjects: Male, 0301 basic medicine, Aging, C9ORF72, Genetic Association Studie, 030105 genetics & heredity, Biology, Settore MED/03 - GENETICA MEDICA, 03 medical and health sciences, 0302 clinical medicine, C9orf72, medicine, Allele, Amyotrophic lateral sclerosis, Amyotrophic lateral sclerosi, Aged, Ataxin-2, Regulator gene, ATXN2, Phenotype, Neuroscience (all), Medicine (all), Developmental Biology, Geriatrics and Gerontology, Neurology (clinical), Genetics, DNA Repeat Expansion, Protein, General Neuroscience, Middle Aged, medicine.disease, 3. Good health, C9orf72 Protein, Italy, Population study, Female, Settore MED/26 - Neurologia, Trinucleotide repeat expansion, 030217 neurology & neurosurgery, Human
Abstract: There are indications that both familial amyotrophic lateral sclerosis (ALS) and sporadic ALS phenotype and prognosis are partly regulated by genetic and environmental factors, supporting the theory that ALS is a multifactorial disease. The aim of this article was to assess the role of ATXN2 intermediate length repeats in a large series of Italian and Sardinian ALS patients and controls carrying a pathogenetic C9ORF72 GGGGCC hexanucleotide repeat. A total of 1972 ALS cases were identified through the database of the Italian ALS Genetic consortium, a collaborative effort including 18 ALS centers throughout Italy. The study population included: (1) 276 Italian and 57 Sardinian ALS cases who carried the C9ORF72 expansion; (2) 1340 Italian and 299 Sardinian ALS cases not carrying the C9ORF72 expansion. A total of healthy 1043 controls were also assessed. Most Italian and Sardinian cases and controls were homozygous for 22/22 or 23/23 repeats or heterozygous for 22/23 repeats of the ATXN2 gene. ATXN2 intermediate length repeats alleles (≥28) were detected in 3 (0.6%) Italian ALS cases carrying the C9ORF72 expansion, in none of the Sardinian ALS cases carrying the expansion, in 60 (4.3%) Italian cases not carrying the expansion, and in 6 (2.0%) Sardinian ALS cases without C9ORF72 expansion. Intermediate length repeat alleles were found in 12 (1.5%) Italian controls and 1 (0.84%) Sardinian controls. Therefore, ALS patients with C9ORF72 expansion showed a lower frequency of ATXN2 polyQ intermediate length repeats than both controls (Italian cases, p = 0.137; Sardinian cases, p = 0.0001) and ALS patients without C9ORF72 expansion (Italian cases, p = 0.005; Sardinian cases, p = 0.178). In our large study on Italian and Sardinian ALS patients with C9ORF72 GGGGCC hexanucleotide repeat expansion, compared to age-, gender- and ethnic-matched controls, ATXN2 polyQ intermediate length does not represent a modifier of ALS risk, differently from non- C9ORF72 mutated patients.
Published: 2015

47. Mutation inCPT1CAssociated With Pure Autosomal Dominant Spastic Paraplegia

Author: Alessandro Filla, Craig Blackstone, Rut Fadó, Leslie G. Biesecker, Carlo Rinaldi, Giuseppe De Michele, Tobias S. Ulmer, Sara Parodi, Benoît Renvoisé, Philip R. Lee, Thomas Schmidt, Alexis Brice, Alexandra Durr, Núria Casals, Christopher Grunseich, Filippo M. Santorelli, Alan J. Situ, Giovanni Stevanin, George H. Harmison, Janel O. Johnson, Laura C. Bott, Bryan J. Traynor, Kenneth H. Fischbeck, Ke lian Chen, Rinaldi, Carlo, Schmidt, Thoma, Situ, Alan J, Johnson, Janel O, Lee, Philip R, Chen, Ke Lian, Bott, Laura C, Fadó, Rut, Harmison, George H, Parodi, Sara, Grunseich, Christopher, Renvoisé, Benoît, Biesecker, Leslie G, DE MICHELE, Giuseppe, Santorelli, Filippo M, Filla, Alessandro, Stevanin, Giovanni, Dürr, Alexandra, Brice, Alexi, Casals, Núria, Traynor, Bryan J, Blackstone, Craig, Ulmer, Tobias S, and Fischbeck, Kenneth H.
Subjects: Adult, Gene isoform, Dominant-Negative Mutation, Biology, Article, Gene product, Mice, Exon, symbols.namesake, Genetic linkage, Animals, Humans, Gene, Exome sequencing, Mice, Knockout, Genetics, Sanger sequencing, Carnitine O-Palmitoyltransferase, Animal, Spastic Paraplegia, Hereditary, Middle Aged, Pedigree, Italy, Mutation, symbols, Neurology (clinical), Human
Abstract: The family of genes implicated in hereditary spastic paraplegias (HSPs) is quickly expanding, mostly owing to the widespread availability of next-generation DNA sequencing methods. Nevertheless, a genetic diagnosis remains unavailable for many patients.To identify the genetic cause for a novel form of pure autosomal dominant HSP.We examined and followed up with a family presenting to a tertiary referral center for evaluation of HSP for a decade until August 2014. Whole-exome sequencing was performed in 4 patients from the same family and was integrated with linkage analysis. Sanger sequencing was used to confirm the presence of the candidate variant in the remaining affected and unaffected members of the family and screen the additional patients with HSP. Five affected and 6 unaffected participants from a 3-generation family with pure adult-onset autosomal dominant HSP of unknown genetic origin were included. Additionally, 163 unrelated participants with pure HSP of unknown genetic cause were screened.Mutation in the neuronal isoform of carnitine palmitoyl-transferase (CPT1C) gene.We identified the nucleotide substitution c.109CT in exon 3 of CPT1C, which determined the base substitution of an evolutionarily conserved Cys residue for an Arg in the gene product. This variant strictly cosegregated with the disease phenotype and was absent in online single-nucleotide polymorphism databases and in 712 additional exomes of control participants. We showed that CPT1C, which localizes to the endoplasmic reticulum, is expressed in motor neurons and interacts with atlastin-1, an endoplasmic reticulum protein encoded by the ATL1 gene known to be mutated in pure HSPs. The mutation, as indicated by nuclear magnetic resonance spectroscopy studies, alters the protein conformation and reduces the mean (SD) number (213.0 [46.99] vs 81.9 [14.2]; P .01) and size (0.29 [0.01] vs 0.26 [0.01]; P .05) of lipid droplets on overexpression in cells. We also observed a reduction of mean (SD) lipid droplets in primary cortical neurons isolated from Cpt1c-/- mice as compared with wild-type mice (1.0 [0.12] vs 0.44 [0.05]; P .001), suggesting a dominant negative mechanism for the mutation.This study expands the genetics of autosomal dominant HSP and is the first, to our knowledge, to link mutation in CPT1C with a human disease. The association of the CPT1C mutation with changes in lipid droplet biogenesis supports a role for altered lipid-mediated signal transduction in HSP pathogenesis.
Published: 2015

48. C9orf72 repeat expansions in patients with ALS and FTD

Author: Rademakers, Rosa, Majounie, Elisa, Renton, Alan E, Mok, Kin, Dopper, Elise G P, Waite, Adrian, Rollinson, Sara, Chiò, Adriano, Restagno, Gabriella, Nicolaou, Nayia, Simon-Sanchez, Javier, van Swieten, John C, Abramzon, Yevgeniya, Johnson, Janel O, Sendtner, Michael, Pamphlett, Roger, Orrell, Richard W, Mead, Simon, Sidle, Katie C, and Houlden, Henry
Subjects: *AGE factors in disease, *AMYOTROPHIC lateral sclerosis, *CHROMOSOMES, *DNA, *GENES, *GENOMES, *LONGITUDINAL method, *RESEARCH funding, *CROSS-sectional method, *FRONTOTEMPORAL dementia, *GENOTYPES
Abstract: Background: We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).Methods: We screened 4448 patients diagnosed with ALS (El Escorial criteria) and 1425 patients with FTD (Lund-Manchester criteria) from 17 regions worldwide for the GGGGCC hexanucleotide expansion using a repeat-primed PCR assay. We assessed familial disease status on the basis of self-reported family history of similar neurodegenerative diseases at the time of sample collection. We compared haplotype data for 262 patients carrying the expansion with the known Finnish founder risk haplotype across the chromosomal locus. We calculated age-related penetrance using the Kaplan-Meier method with data for 603 individuals with the expansion.Findings: In patients with sporadic ALS, we identified the repeat expansion in 236 (7·0%) of 3377 white individuals from the USA, Europe, and Australia, two (4·1%) of 49 black individuals from the USA, and six (8·3%) of 72 Hispanic individuals from the USA. The mutation was present in 217 (39·3%) of 552 white individuals with familial ALS from Europe and the USA. 59 (6·0%) of 981 white Europeans with sporadic FTD had the mutation, as did 99 (24·8%) of 400 white Europeans with familial FTD. Data for other ethnic groups were sparse, but we identified one Asian patient with familial ALS (from 20 assessed) and two with familial FTD (from three assessed) who carried the mutation. The mutation was not carried by the three Native Americans or 360 patients from Asia or the Pacific Islands with sporadic ALS who were tested, or by 41 Asian patients with sporadic FTD. All patients with the repeat expansion had (partly or fully) the founder haplotype, suggesting a one-off expansion occurring about 1500 years ago. The pathogenic expansion was non-penetrant in individuals younger than 35 years, 50% penetrant by 58 years, and almost fully penetrant by 80 years.Interpretation: A common Mendelian genetic lesion in C9orf72 is implicated in many cases of sporadic and familial ALS and FTD. Testing for this pathogenic expansion should be considered in the management and genetic counselling of patients with these fatal neurodegenerative diseases.Funding: Full funding sources listed at end of paper (see Acknowledgments). [ABSTRACT FROM AUTHOR]
Published: 2012
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49. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene.

Author: Nicolas A, Kenna KP, Renton AE, Ticozzi N, Faghri F, Chia R, Dominov JA, Kenna BJ, Nalls MA, Keagle P, Rivera AM, van Rheenen W, Murphy NA, van Vugt JJFA, Geiger JT, Van der Spek RA, Pliner HA, Shankaracharya, Smith BN, Marangi G, Topp SD, Abramzon Y, Gkazi AS, Eicher JD, Kenna A, Mora G, Calvo A, Mazzini L, Riva N, Mandrioli J, Caponnetto C, Battistini S, Volanti P, La Bella V, Conforti FL, Borghero G, Messina S, Simone IL, Trojsi F, Salvi F, Logullo FO, D'Alfonso S, Corrado L, Capasso M, Ferrucci L, Moreno CAM, Kamalakaran S, Goldstein DB, Gitler AD, Harris T, Myers RM, Phatnani H, Musunuri RL, Evani US, Abhyankar A, Zody MC, Kaye J, Finkbeiner S, Wyman SK, LeNail A, Lima L, Fraenkel E, Svendsen CN, Thompson LM, Van Eyk JE, Berry JD, Miller TM, Kolb SJ, Cudkowicz M, Baxi E, Benatar M, Taylor JP, Rampersaud E, Wu G, Wuu J, Lauria G, Verde F, Fogh I, Tiloca C, Comi GP, Sorarù G, Cereda C, Corcia P, Laaksovirta H, Myllykangas L, Jansson L, Valori M, Ealing J, Hamdalla H, Rollinson S, Pickering-Brown S, Orrell RW, Sidle KC, Malaspina A, Hardy J, Singleton AB, Johnson JO, Arepalli S, Sapp PC, McKenna-Yasek D, Polak M, Asress S, Al-Sarraj S, King A, Troakes C, Vance C, de Belleroche J, Baas F, Ten Asbroek ALMA, Muñoz-Blanco JL, Hernandez DG, Ding J, Gibbs JR, Scholz SW, Floeter MK, Campbell RH, Landi F, Bowser R, Pulst SM, Ravits JM, MacGowan DJL, Kirby J, Pioro EP, Pamphlett R, Broach J, Gerhard G, Dunckley TL, Brady CB, Kowall NW, Troncoso JC, Le Ber I, Mouzat K, Lumbroso S, Heiman-Patterson TD, Kamel F, Van Den Bosch L, Baloh RH, Strom TM, Meitinger T, Shatunov A, Van Eijk KR, de Carvalho M, Kooyman M, Middelkoop B, Moisse M, McLaughlin RL, Van Es MA, Weber M, Boylan KB, Van Blitterswijk M, Rademakers R, Morrison KE, Basak AN, Mora JS, Drory VE, Shaw PJ, Turner MR, Talbot K, Hardiman O, Williams KL, Fifita JA, Nicholson GA, Blair IP, Rouleau GA, Esteban-Pérez J, García-Redondo A, Al-Chalabi A, Rogaeva E, Zinman L, Ostrow LW, Maragakis NJ, Rothstein JD, Simmons Z, Cooper-Knock J, Brice A, Goutman SA, Feldman EL, Gibson SB, Taroni F, Ratti A, Gellera C, Van Damme P, Robberecht W, Fratta P, Sabatelli M, Lunetta C, Ludolph AC, Andersen PM, Weishaupt JH, Camu W, Trojanowski JQ, Van Deerlin VM, Brown RH Jr, van den Berg LH, Veldink JH, Harms MB, Glass JD, Stone DJ, Tienari P, Silani V, Chiò A, Shaw CE, Traynor BJ, and Landers JE
Subjects: Adult, Aged, Aged, 80 and over, Amino Acid Sequence, Amyotrophic Lateral Sclerosis epidemiology, Cohort Studies, Female, Humans, Male, Middle Aged, Young Adult, Amyotrophic Lateral Sclerosis diagnosis, Amyotrophic Lateral Sclerosis genetics, Genome-Wide Association Study methods, Kinesins genetics, Loss of Function Mutation genetics
Abstract: To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS., (Copyright © 2018 Elsevier Inc. All rights reserved.)
Published: 2018
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50. Small deletion in C9orf72 hides a proportion of expansion carriers in FTLD.

Author: Rollinson S, Bennion Callister J, Young K, Ryan SJ, Druyeh R, Rohrer JD, Snowden J, Richardson A, Jones M, Harris J, Davidson Y, Robinson A, Ealing J, Johnson JO, Traynor B, Mead S, Mann D, and Pickering-Brown SM
Subjects: Adult, Aged, Aged, 80 and over, C9orf72 Protein, Cohort Studies, Female, Frontotemporal Lobar Degeneration epidemiology, Genetic Testing methods, Humans, Male, Middle Aged, Polymerase Chain Reaction methods, Sequence Analysis, DNA methods, Young Adult, DNA Repeat Expansion genetics, Frontotemporal Lobar Degeneration genetics, Gene Deletion, Heterozygote, Mutation genetics, Proteins genetics
Abstract: Frontotemporal lobar degeneration is a highly familial disease and the most common known genetic cause is the repeat expansion mutation in the gene C9orf72. We have identified 2 brothers with an expansion mutation in C9orf72 using Southern blotting that is undetectable using repeat-primed polymerase chain reaction. Sequencing using high concentrations of DNA denaturants of a bacterial artificial chromosome clone obtained from one of the brothers identified a 10-base pair deletion adjacent to the expansion that presumably confers strong secondary structure that interferes with the genotyping. Using an alternative method, we have identified missed expansion carriers in our cohort, and this number has increased by approximately 25%. This observation has important implications for patients undergoing genetic testing for C9orf72., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2015
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