Searched for: person:brownr07
Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis
Dewan, Ramita; Chia, Ruth; Ding, Jinhui; Hickman, Richard A; Stein, Thor D; Abramzon, Yevgeniya; Ahmed, Sarah; Sabir, Marya S; Portley, Makayla K; Tucci, Arianna; Ibáñez, Kristina; Shankaracharya, F N U; Keagle, Pamela; Rossi, Giacomina; Caroppo, Paola; Tagliavini, Fabrizio; Waldo, Maria L; Johansson, Per M; Nilsson, Christer F; Rowe, James B; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Jabbari, Edwin; Viollet, Coralie; Glass, Jonathan D; Singleton, Andrew B; Silani, Vincenzo; Ross, Owen A; Ryten, Mina; Torkamani, Ali; Tanaka, Toshiko; Ferrucci, Luigi; Resnick, Susan M; Pickering-Brown, Stuart; Brady, Christopher B; Kowal, Neil; Hardy, John A; Van Deerlin, Vivianna; Vonsattel, Jean Paul; Harms, Matthew B; Morris, Huw R; Ferrari, Raffaele; Landers, John E; Chiò, Adriano; Gibbs, J Raphael; Dalgard, Clifton L; Scholz, Sonja W; Traynor, Bryan J; Adeleye, Adelani; Alba, Camille; Bacikova, Dagmar; Hupalo, Daniel N; Martinez, Elisa McGrath; Pollard, Harvey B; Sukumar, Gauthaman; Soltis, Anthony R; Tuck, Meila; Zhang, Xijun; Wilkerson, Matthew D; Smith, Bradley N; Ticozzi, Nicola; Fallini, Claudia; Gkazi, Athina Soragia; Topp, Simon D; Kost, Jason; Scotter, Emma L; Kenna, Kevin P; Miller, Jack W; Tiloca, Cinzia; Vance, Caroline; Danielson, Eric W; Troakes, Claire; Colombrita, Claudia; Al-Sarraj, Safa; Lewis, Elizabeth A; King, Andrew; Calini, Daniela; Pensato, Viviana; Castellotti, Barbara; de Belleroche, Jacqueline; Baas, Frank; Ten Asbroek, Anneloor L M A; Sapp, Peter C; McKenna-Yasek, Diane; McLaughlin, Russell L; Polak, Meraida; Asress, Seneshaw; Esteban-Pérez, Jesús; Muñoz-Blanco, José Luis; Stevic, Zorica; D'Alfonso, Sandra; Mazzini, Letizia; Comi, Giacomo P; Del Bo, Roberto; Ceroni, Mauro; Gagliardi, Stella; Querin, Giorgia; Bertolin, Cinzia; van Rheenen, Wouter; Diekstra, Frank P; Rademakers, Rosa; van Blitterswijk, Marka; Boylan, Kevin B; Lauria, Giuseppe; Duga, Stefano; Corti, Stefania; Cereda, Cristina; Corrado, Lucia; Sorarù, Gianni; Williams, Kelly L; Nicholson, Garth A; Blair, Ian P; Leblond-Manry, Claire; Rouleau, Guy A; Hardiman, Orla; Morrison, Karen E; Veldink, Jan H; van den Berg, Leonard H; Al-Chalabi, Ammar; Pall, Hardev; Shaw, Pamela J; Turner, Martin R; Talbot, Kevin; Taroni, Franco; GarcÃa-Redondo, Alberto; Wu, Zheyang; Gellera, Cinzia; Ratti, Antonia; Brown, Robert H Jr; Shaw, Christopher E; Ambrose, John C; Arumugam, Prabhu; Baple, Emma L; Bleda, Marta; Boardman-Pretty, Freya; Boissiere, Jeanne M; Boustred, Christopher R; Brittain, H; Caulfield, Mark J; Chan, Georgia C; Craig, Clare E H; Daugherty, Louise C; de Burca, Anna; Devereau, Andrew; Elgar, Greg; Foulger, Rebecca E; Fowler, Tom; Furió-TarÃ, Pedro; Hackett, Joanne M; Halai, Dina; Hamblin, Angela; Henderson, Shirley; Holman, James E; Hubbard, Tim J P; Jackson, Rob; Jones, Louise J; Kasperaviciute, Dalia; Kayikci, Melis; Lahnstein, Lea; Lawson, Kay; Leigh, Sarah E A; Leong, Ivonne U S; Lopez, Javier F; Maleady-Crowe, Fiona; Mason, Joanne; McDonagh, Ellen M; Moutsianas, Loukas; Mueller, Michael; Murugaesu, Nirupa; Need, Anna C; Odhams, Chris A; Patch, Christine; Perez-Gil, Daniel; Polychronopoulos, Dimitris; Pullinger, John; Rahim, Tahrima; Rendon, Augusto; Riesgo-Ferreiro, Pablo; Rogers, Tim; Savage, Kevin; Sawant, Kushmita; Scott, Richard H; Siddiq, Afshan; Sieghart, Alexander; Smedley, Damian; Smith, Katherine R; Sosinsky, Alona; Spooner, William; Stevens, Helen E; Stuckey, Alexander; Sultana, Razvan; Thomas, Ellen R A; Thompson, Simon R; Tregidgo, Carolyn; Walsh, Emma; Watters, Sarah A; Welland, Matthew J; Williams, Eleanor; Witkowska, Katarzyna; Wood, Suzanne M; Zarowiecki, Magdalena; Arepalli, Sampath; Auluck, Pavan; Baloh, Robert H; Bowser, Robert; Brice, Alexis; Broach, James; Camu, William; Chiò, Adriano; Cooper-Knock, John; Corcia, Philippe; Drepper, Carsten; Drory, Vivian E; Dunckley, Travis L; Faghri, Faraz; Farren, Jennifer; Feldman, Eva; Floeter, Mary Kay; Fratta, Pietro; Gerhard, Glenn; Gibson, Summer B; Goutman, Stephen A; Heiman-Patterson, Terry D; Hernandez, Dena G; Hoover, Ben; Jansson, Lilja; Kamel, Freya; Kirby, Janine; Kowall, Neil W; Laaksovirta, Hannu; Landi, Francesco; Le Ber, Isabelle; Lumbroso, Serge; MacGowan, Daniel Jl; Maragakis, Nicholas J; Mora, Gabriele; Mouzat, Kevin; Myllykangas, Liisa; Nalls, Mike A; Orrell, Richard W; Ostrow, Lyle W; Pamphlett, Roger; Pioro, Erik; Pulst, Stefan M; Ravits, John M; Renton, Alan E; Robberecht, Wim; Robey, Ian; Rogaeva, Ekaterina; Rothstein, Jeffrey D; Sendtner, Michael; Shaw, Pamela J; Sidle, Katie C; Simmons, Zachary; Stone, David J; Tienari, Pentti J; Trojanowski, John Q; Troncoso, Juan C; Valori, Miko; Van Damme, Philip; Van Den Bosch, Ludo; Zinman, Lorne; Albani, Diego; Borroni, Barbara; Padovani, Alessandro; Bruni, Amalia; Clarimon, Jordi; Dols-Icardo, Oriol; Illán-Gala, Ignacio; Lleó, Alberto; Danek, Adrian; Galimberti, Daniela; Scarpini, Elio; Serpente, Maria; Graff, Caroline; Chiang, Huei-Hsin; Khoshnood, Behzad; Öijerstedt, Linn; Morris, Christopher M; Nacmias, Benedetta; Sorbi, Sandro; Nielsen, Jorgen E; Hjermind, Lynne E; Novelli, Valeria; Puca, Annibale A; Pastor, Pau; Alvarez, Ignacio; Diez-Fairen, Monica; Aguilar, Miquel; Perneczky, Robert; Diehl-Schimd, Janine; Rogaeva, Ekaterina; Rossi, Mina; Ruiz, Agustin; Boada, Mercè; Hernández, Isabel; Moreno-Grau, Sonia; Schlachetzki, Johannes C; Aarsland, Dag; Alba, Camille; Albert, Marilyn S; Al-Sarraj, Safa; Attems, Johannes; Bacikova, Dagmar; Barrett, Matthew J; Beach, Thomas G; Bekris, Lynn M; Bennett, David A; Besser, Lilah M; Bigio, Eileen H; Black, Sandra E; Boeve, Bradley F; Bohannan, Ryan C; Brett, Francesca; Brice, Alexis; Brunetti, Maura; Caraway, Chad A; Palma, Jose-Alberto; Calvo, Andrea; Canosa, Antonio; Clarimon, Jordi; Dickson, Dennis; Diez-Fairen, Monica; Duyckaerts, Charles; Faber, Kelley; Ferman, Tanis; Flanagan, Margaret E; Floris, Gianluca; Foroud, Tatiana M; Fortea, Juan; Gan-Or, Ziv; Gentleman, Steve; Ghetti, Bernardino; Gibbs, Jesse Raphael; Goate, Alison; Goldstein, David; González-Aramburu, Isabel; Graff-Radford, Neill R; Hodges, Angela K; Hu, Heng-Chen; Hupalo, Daniel; Infante, Jon; Iranzo, Alex; Kaiser, Scott M; Kaufmann, Horacio; Keith, Julia; Kim, Ronald C; Klein, Gregory; Krüger, Rejko; Kukull, Walter; Kuzma, Amanda; Lage, Carmen; Lesage, Suzanne; Lleó, Alberto; Leverenz, James B; Logroscino, Giancarlo; Lopez, Grisel; Love, Seth; Mao, Qinwen; Marti, Maria Jose; Martinez-McGrath, Elisa; Masellis, Mario; Masliah, Eliezer; May, Patrick; McKeith, Ian; Mesulam, Marek-Marsel; Monuki, Edwin S; Morris, Christopher M; Newell, Kathy L; Norcliffe-Kaufmann, Lucy; Palmer, Laura; Pastor, Pau; Perkins, Matthew; Pletnikova, Olga; Molina-Porcel, Laura; Renton, Alan E; Reynolds, Regina H; RodrÃguez-RodrÃguez, Eloy; Rogaeva, Ekaterina; Rohrer, Jonathan D; Sanchez-Juan, Pascual; Scherzer, Clemens R; Serrano, Geidy E; Shakkottai, Vikram; Sidransky, Ellen; Tayebi, Nahid; Thomas, Alan J; Tilley, Bension S; Troakes, Claire; Troncoso, Juan C; Walton, Ronald L; Woltjer, Randy; Wszolek, Zbigniew K; Xiromerisiou, Georgia; Zecca, Chiara; Phatnani, Hemali; Kwan, Justin; Sareen, Dhruv; Broach, James R; Simmons, Zachary; Arcila-Londono, Ximena; Lee, Edward B; Shneider, Neil A; 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; Miller, Timothy M; Chandran, Siddharthan; Pal, Suvankar; Hornstein, Eran; MacGowan, Daniel J; Heiman-Patterson, Terry; Hammell, Molly G; Patsopoulos, Nikolaos A; Butovsky, Oleg; Dubnau, Joshua; Nath, Avindra; Bowser, Robert; Harms, Matt; Aronica, Eleonora; Poss, Mary; Phillips-Cremins, Jennifer; Crary, John; Atassi, Nazem; Lange, Dale J; Adams, Darius J; Stefanis, Leonidas; Gotkine, Marc; Baloh, Robert H; Babu, Suma; Raj, Towfique; Paganoni, Sabrina; Shalem, Ophir; Smith, Colin; Zhang, Bin; Harris, Brent; Broce, Iris; Drory, Vivian; Ravits, John; McMillan, Corey; Menon, Vilas; Wu, Lani; Altschuler, Steven; Amar, Khaled; Archibald, Neil; Bandmann, Oliver; Capps, Erica; Church, Alistair; Coebergh, Jan; Costantini, Alyssa; Critchley, Peter; Ghosh, Boyd Cp; Hu, Michele T M; Kobylecki, Christopher; Leigh, P Nigel; Mann, Carl; Massey, Luke A; Morris, Huw R; Nath, Uma; Pavese, Nicola; Paviour, Dominic; Sharma, Jagdish; Vaughan, Jenny
We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered.
PMID: 33242422
ISSN: 1097-4199
CID: 5429222
Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
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; 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; 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 Luis; 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, 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, Jesús; GarcÃa-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; 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; 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; Tranquilli, Stefania; 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, George; 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; Baloh, Robert H; 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; Gibson, Summer; Gitler, Aaron D; Glass, Jonathan D; Goldstein, David B; Han, Yujun; Harms, Matthew B; 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; Miller, Timothy M; Myers, Richard M; Petrovski, Slavé; Pulst, Stefan M; Raphael, Alya R; Ravits, John M; Ren, Zhong; Rouleau, Guy A; Sapp, Peter C; Shneider, Neil A; Simpson, Ericka; Sims, Katherine B; Staropoli, John F; Waite, Lindsay L; Wang, Quanli; Wimbish, Jack R; Xin, Winnie W; Phatnani, Hemali; Kwan, Justin; Sareen, Dhruv; Broach, James R; Simmons, Zachary; Arcila-Londono, Ximena; Lee, Edward B; Van Deerlin, Vivianna M; Shneider, Neil A; 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; Miller, Timothy M; Chandran, Siddharthan; Pal, Suvankar; 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; Fraenkel, Ernest; Rothstein, Jeffrey D; Svendsen, Clive N; Thompson, Leslie M; Van Eyk, Jenny; Maragakis, Nicholas J; Berry, James D; Glass, Jonathan D; Miller, Timothy M; Kolb, Stephen J; Baloh, Robert H; 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; Corcia, Philippe; Couratier, Philippe; 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; Silani, Vincenzo; Sproviero, William; Tazelaar, Gijs; Ticozzi, Nicola; 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
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.
PMCID:5867896
PMID: 29566793
ISSN: 1097-4199
CID: 5429242
The Advanced Glaucoma Intervention Study, 8: Risk of cataract formation after trabeculectomy
Blackwell, B; Ederer, F; Van Veldhuisen, PC; Sullivan, EK; Dally, LG; Weber, PA; Miller, E; Katz, LJ; Ashburn, F; Beck, A; Costarides, A; Leef, D; Closek, J; Banks, J; Jackson, S; Moore, K; Vela, A; Brown, RH; Lynch, M; Gunsby, J; Lober, K; Marsh, T; Stepka, C; Montgomery, R; Clagett, D; Ashburn, F; Schacht, K; Coyle, E; Garland, MK; Lauber, S; Michelitsch, K; Plavnieks, S; Vayer, L; Burt, E; Hundley, M; Rae, A; Allen, RC; Miller, E; Sporn, A; Fendley, CK; Hoyle, LS; Weber, PA; McKinney, K; Moore, D; Lauderbaugh, T; Baker, ND; Kapetansky, F; Lehmann, D; Black, L; Derick, R; Gloeckner, B; Coleman, K; Cassady, M; Sharf, LJ; Romans, B; Satterwhite, Y; Simmons, L; Vela, MA; Harbin, TS; Brannon, L; LaSalle, J; Degenhardt, G; Bridgman, SA; Ozment, RR; Gunsby, J; Hooper, M; Wright, J; Goldstein, S; Butler, L; Perry, M; Eckel, A; Martin, A; Nummerdor, D; Wille, L; Cyrlin, MN; Dubay, H; Fazio, R; Corbin, PS; Wilensky, JT; Lindenmuth, K; Hillman, D; Carroll, CA; Hatton, J; Sonty, S; Carroll, CA; Higginbotham, EJ; Scholes, G; Uva, R; Fiene, J; Frohlichstein, D; Gates, V; Pappas, L; Rathbone, D; Tadelman, M; Hopkins, G; Lichter, PR; Bergstrom, TJ; Moroi, SE; Pollack-Rundle, CJ; Standardi, C; Abt, L; Van Heck, T; Skuta, GL; Higginbotham, EJ; Schertzer, RM; Wicker, D; Michael, B; Aaron, D; Birk, J; Brown, RS; Dederian, J; Kruscke, L; Ziehm-Scott, J; Papierniak-Dubiel, R; Prum, BE; Newman, SA; Powell, L; Evans, C; Barbour, N; Shoffstall-Tyler, L; Voight, T; Nordlund, JR; Schott, LJ; Fornili, R; Chisholm, J; Harrell, C; Harris, C; Murphy, E; Schwartz, AL; Weiss, H; Boeckl, A; Tillman, C; Boeckl, A; Maloney, L; Cirone, M; Gurley, J; Morris, M; O'Dea, M; Pappas, S; Wehrly, S; Reed, C; Witol, CV; Browning, J; Carmody, K; Driskell, T; Harris, E; Lopez, P; Mercer, R; Monks, V; Vawter, K; Zhao, J; Katz, LJ; Spaeth, GL; Wilson, RP; Myers, J; Samuel, F; Meli, A; Kao, S; Terebuh, A; Beckershoff, CC; Shields, MB; Shafranov, G; Leone, A; Grottole, G; Miller, E; Caprioli, J; Tressler, C; Roche-Manna, M; VanVeldhuisen, PC; Ederer, F; Dally, LG; Blackwell, B; Inman, P; Raitt, S; Lindblad, AS; Knoke, JD; Sullivan, EK; Wu, LL; Entler, G; Phillips, P; Smith, C; Bradford, M; Denekas, M; Wagner, EL; Stine, E; Tomlin, KL; Voss, T; Furberg, CD; Connett, JE; Davis, MD; Dueker, DK; Green, SB; Palmberg, PF; Ederer, F; Gaasterland, DE; Cotch, MF; Leikin, S; Schneiderman, M; Hamilton, MP; Mowery, RL; VanVeldhuisen, PC; Schwartz, AL; Lindblad, AS; Knoke, JD; Sullivan, EK; Schwartz, AL; Kassoff, A; Cotch, MF; Cyrlin, MN; Vela, MA; Caprioli, J; Higginbotham, EJ; Skuta, GL; Katz, LJ; Weber, PA; Allen, RC; Wilensky, JT; Miller, E; Brown, R; Prum, B; Cyrlin, M; Beck, A; Lichter, P; Leef, D; McKinney, K; Reed, C; Uva, R; Samuel, F; Roche-Manna, M; Standardi, C; Coyle, E; Boeckl, A; Pollack-Rundle, CJ; Carroll, CA; Sporn, A; Leone, A; Mowery, RL; Kassoff, A; Katz, LJ; Leef, D; Skuta, GL; Samuel, F; Lindblad, AS; Reed, C; Beckershoff, CC; Entler, G; Wagner, EL; AGIS Investigators
Objectives: To compare the risk of cataract formation in eyes with and without prior trabeculectomy and to assess other risk factors for cataract. Methods: The Advanced Glaucoma Intervention Study (AGIS) has been following 789 eyes in 591 patients with medically uncontrolled open-angle glaucoma. From 1988 to 1992, these eyes were randomly assigned to either an argon laser trabeculoplasty (ALT)-trabeculectomy-trabeculectomy treatment sequence or a trabeculectomy-ALT-trabeculectomy sequence. Cox regression analyses were used to assess risk factors for cataract formation during 7 to 11 years of follow-up. Main Outcome Measures: Cataract, defined as either having had cataract surgery or confirmed severe lens opacity with a best-corrected Early Treatment Diabetic Retinopathy Study visual acuity score less than 65 letters (worse than 20/50). Results: Data are presented on the expected 5-year cumulative probability of cataract formation in each randomized sequence by age and presence of diabetes at study entry. Overall, approximately half of the eyes studied developed cataract. A first trabeculectomy, whether as the first or second AGIS intervention, increased the overall risk of cataract by 78% (risk ratio [RR]=1.78; P < .001). Diabetes (RR=1.47; P=.004) and age at study entry (RR=1.07 per year of age; P < .001) were also risk factors for cataract. When postoperative complications of trabeculectomy were included in the analysis, the increased risk of cataract for eyes with a first trabeculectomy reduced to 47% when complications did not occur (RR=1.47; P=.003) and increased to 104% when complications did occur (RR=2.04; P < .001). Several specific postoperative complications of trabeculectomy were associated with increased risk of cataract, particularly marked inflammation (RR=3.29; P < .001) and flat anterior chamber (RR=1.80; P=.004). Trabeculectomy with complications was also significantly associated with an increased risk of cataract in each of 3 lens regions: nuclear, cortical, and posterior subcapsular. Conclusions: In eyes of AGIS patients, after adjustment for age and diabetes, trabeculectomy increased the risk of cataract formation by 78%. $$:
ISI:000172586600003
ISSN: 0003-9950
CID: 103769
Glaucoma surgery treatment patterns of ASCRS members--2000 survey
Johnstone, M A; Shingleton, B J; Crandall, A S; Brown, R H; Robin, A L
A survey of glaucoma surgery parameters was mailed to all the United States members of the American Society of Cataract and Refractive Surgery in 1999 and 2000. Of the 5659 surveys mailed, 725 (13%) were returned. The survey assessed parameters used in glaucoma surgical treatment. Preferred surgery treatment patterns were cross-tabulated with fellowship training in glaucoma (9.3%) and geographic location. This report summarizes current practice styles and patterns of comprehensive ophthalmologists in the United States as derived from the survey.
PMID: 11709262
ISSN: 0886-3350
CID: 1736922
The advanced glaucoma intervention study, 6: Effect of cataract on visual field and visual acuity
Ederer, F; Sullivan, EK; Van Veldhuisen, PC; Gaasterland, DE; Wu, LL; Sonty, S; Beck, A; Schwartz, AL; Prum, BE; Costarides, A; Leef, D; Closek, J; Banks, J; Jackson, S; Moore, K; Vela, A; Brown, RH; Lynch, M; Gunsby, J; Lober, K; Marsh, T; Stepka, C; Montgomery, R; Clagett, D; Ashburn, F; Schacht, K; Coyle, E; Garland, MK; Lauber, S; Michelitsch, K; Plavnieks, S; Vayer, L; Burt, E; Hundley, M; Rae, A; Allen, RC; Miller, E; Sporn, A; Fendley, CK; Hoyle, LS; Weber, PA; McKinney, K; Moore, D; Lauderbaugh, T; Baker, ND; Kapetansky, F; Lehmann, D; Black, L; Derick, R; Gloeckner, B; Coleman, K; Cassady, M; Sharf, LJ; Romans, B; Satterwhite, Y; Simmons, L; Vela, MA; Harbin, TS; Brannon, L; Wright, J; LaSalle, J; Degenhardt, G; Bridgman, SA; Ozment, RR; Hooper, M; Goldstein, S; Butler, L; Perry, M; Eckel, A; Martin, A; Session, C; Nummerdor, D; Wille, L; Cyrlin, MN; Dubay, H; Fazio, R; Corbin, PS; Wilensky, JT; Lindenmuth, K; Hillman, D; Carroll, CA; Hatton, J; Carroll, CA; Higginbotham, EJ; Scholes, G; Uva, R; Fiene, J; Frohlichstein, D; Gates, V; Pappas, L; Rathbone, D; Tadelman, M; Hopkins, G; Lichter, PR; Bergstrom, TJ; Moroi, SE; Pollack-Rundle, CJ; Standardi, C; Abt, L; Van Heck, T; Skuta, GL; Higginbotham, EJ; Schertzer, RM; Wicker, D; Michael, B; Aaron, D; Birk, J; Brown, RS; Dederian, J; Kruscke, L; Ziehm-Scott, J; Papierniak-Dubiel, R; Prum, BE; Newman, SA; Powell, L; Evans, C; Barbour, N; Shoffstall-Tyler, L; Voight, T; Nordlund, JR; Schott, LJ; Fornili, R; Chisholm, J; Harrell, C; Harris, C; Murphy, E; Schwartz, AL; Weiss, H; Boeckl, A; Tillman, C; Boeckl, A; Maloney, L; Cirone, M; Gurley, J; Morris, M; O'Dea, M; Pappas, S; Wehrly, S; Reed, C; Witol, CV; Browning, J; Carmody, K; Driskell, T; Harris, E; Lopez, P; Mercer, R; Monks, V; Vawter, K; Zhao, J; Katz, LJ; Spaeth, GL; Wilson, RP; Myers, J; Samuel, F; Meli, A; Kao, S; Terebuh, A; Beckershoff, CC; Shields, MB; Shafranov, G; Leone, A; Grottole, G; Miller, E; Caprioli, J; Tressler, C; Roche-Manna, M; VanVeldhuisen, PC; Dally, LG; Blackwell, B; Inman, P; Raitt, S; Lindblad, AS; Knoke, JD; Sullivan, EK; Wu, LL; Entler, G; Phillips, P; Smith, C; Bradford, M; Denekas, M; Wagner, EL; Stine, E; Tomlin, KL; Voss, T; Cotch, MF; Darby, WW; Mowery, RL; Goff, F; Grimes, C; Lynch, G; Furberg, CD; Connett, JE; Daivs, MD; Dueker, DK; Green, SB; Palmberg, PF; Cotch, MF; Leikin, S; Schneiderman, M; Hamilton, MP; Mowery, RL; Schwartz, AL; Lindblad, AS; Knoke, JD; Sullivan, EK; Ederer, F; Schwartz, AL; Kassoff, A; Cotch, MF; Cyrlin, MN; Vela, MA; Caprioli, J; Higginbotham, EJ; Skuta, GL; Katz, LJ; Weber, PA; Allen, RC; Wilensky, JT; Miller, E; Brown, R; Prum, B; Cyrlin, M; Lichter, P; Leef, D; McKinney, K; Reed, C; Uva, R; Samuel, F; Manna, MR; Standardi, C; Coyle, E; Boeckl, A; Pollack-Rundle, CJ; Carroll, CA; Sporn, A; Leone, A; Mowery, RL; Kassoff, A; Katz, LJ; Leef, D; Skuta, GL; Standardi, C; Samuel, F; Lindblad, AS; Reed, C; Beckershoff, CC; Entler, G; Wagner, EL; AGIS Investigators
Objective: To investigate the effect of cataract on visual function and the role of cataract in explaining a race-treatment interaction in outcomes of glaucoma surgery. Methods; The Advanced Glaucoma Intervention Study (AGIS) enrolled 332 black patients (451 eyes) and 249 white patients (325 eyes) with advanced glaucoma. Eyes were randomly assigned to an argon laser trabeculoplasty (ALT)-trabeculectomy-trabeculectomy sequence or a trabeculectomy-ALT-trabeculectomy sequence. From the AGIS experience with cataract surgery during followup, we estimated the expected change in visual function scores from before cataract surgery to after. cataract surgery. Then, for eyes with cataract not removed, we used these estimates of expected change to adjust visual function scores for the presumed effects of cataract. in turn, we used the adjusted scores to obtain cataract-adjusted main outcome measures. Main Outcome Measures: Average percent of eyes with decrease of visual field (APDVF) and average percent of eyes with decrease of visual acuity (APDVA). Results: Within the 2 months before cataract surgery, visual acuity was better ill eyes of white patients than of black patients by an average of approximately 2 lines on the visual acuity test chart. Cataract surgery improved visual acuity and visual field defect scores, with the amounts of improvement greater when preoperative visual acuity was lower. Adjustments for cataract brought about the following relative reductions: for APDVF, a relative reduction of 5% to 11% in black patients and 9% to 11% in white patients; for APDVA, a relative reduction of 45% to 49% in black patients and 31% to 38%, in white patients; and for the APDVF and APDVA race-treatment interactions, relative reductions of 25% and 45%, respectively. Conclusions: On average, visual function scores improved after cataract surgery. The findings of reduced race treatment interactions after adjustment for cataract do not alter our earlier conclusion that the AGIS 7-year results support use of the ALT-trabeculectomy trabeculectomy sequence for black patients and of the trabeculectomy-ALT-trabeculectomy sequence for white patients without life-threatening health problems. The choice of treatment should take into account individual patient characteristics and needs. $$:
ISI:000165738800004
ISSN: 0003-9950
CID: 103770
Glaucoma laser treatment parameters and practices of ASCRS members--1999 survey. American Society of Cataract and Refractive Surgery
Brown, R H; Shingleton, B J; Johnstone, M; Crandall, A; Robin, A
A survey of glaucoma laser parameters and practices was mailed to all United States members of the American Society of Cataract and Refractive Surgery (ASCRS) in March 1999. Approximately 19% (947) of the 5100 surveys were returned. The survey assessed parameters used for laser trabeculoplasty, laser iridotomy, and gonioplasty. Respondents also answered questions about the application of these laser therapies in a wide variety of clinical situations. The results were cross-tabulated by age, number of laser trabeculoplasties performed per month, fellowship training in glaucoma, and geographic location.
PMID: 10831908
ISSN: 0886-3350
CID: 1736912
Remodeling filtering blebs with the neodymium:YAG laser
Lynch, M G; Roesch, M; Brown, R H
PURPOSE: To describe a new method of treating large, overfiltering, leaking blebs using a continuous-wave neodymium:YAG laser. METHODS: Twenty-three eyes of 23 patients underwent YAG laser remodeling because of overfiltration and hypotony (group 1; n = 14); leaking bleb and hypotony (group 2; n = 5); and large, irritating bleb (group 3; n = 4). Using a neodymium:YAG laser in the continuous-wave multimode, a grid pattern of laser treatment was placed over the entire bleb using energy levels between 3.0 and 4.0 J and a laser offset between 0.9 and 1.2 mm. A torpedo patch then was placed directly over the bleb for 48 hours. Steroid therapy was avoided. RESULTS: In group 1, 64% of eyes had an intraocular pressure increase of at least 3.0 mmHg. In group 2, 80% of bleb leaks were sealed. In group 3, 100% of patients had resolution of their discomfort. The elevation in intraocular pressure peaked at 1 to 3 months and diminished thereafter. There was improvement in vision of at least two Snellen acuity lines in 52% of eyes. Complications included the need for laser retreatment (7 eyes), creation of temporary bleb leak by the YAG laser (2 eyes), transient increase in intraocular pressure (2 eyes), and corneal edema (1 eye). CONCLUSION: The continuous-wave neodymium:YAG laser can be used to effectively change the appearance and behavior of filtering blebs, although the duration of treatment effect is unknown.
PMID: 8874446
ISSN: 0161-6420
CID: 1736472
Neodymium: YAG membranectomy for pupillary membranes on posterior chamber intraocular lenses [Case Report]
Gandham, S B; Brown, R H; Katz, L J; Lynch, M G
PURPOSE: To evaluate the effectiveness of neodymium: YAG laser for the removal of membranes from the anterior surface of intraocular lenses. METHODS: Seven patients had reduced vision due to a membrane on the anterior surface of a posterior chamber intraocular lens (PC IOL). Six of the membranes developed after extracapsular cataract surgery and PC IOL combined with trabeculectomy and one after pars plana vitrectomy. Six of the membranes developed in the early postoperative period in association with a fibrinous reaction of the anterior chamber. One formed 7 months after surgery in an eye with iris capture behind the IOL. The membranes persisted despite intensive topical steroid therapy. A neodymium: YAG (Nd:YAG) laser was used to remove the membranes from the anterior of the IOL in all the seven cases. RESULTS: The Nd:YAG laser effectively severed the peripheral connections of the membranes to the iris and lens, creating a clear central zone within the visual axis. The settings were fundamental mode, 1.2-to 3.1-mJ energy per shot and 48.3 +/- 20.1 single pulses. Vision improved significantly in six patients, whereas elevated intraocular pressure was observed in one patient. CONCLUSION: Postoperative pupillary membranes may be successfully lysed with use of the Nd:YAG laser.
PMID: 9098286
ISSN: 0161-6420
CID: 1736482
The use of a new laser lens holder for performing suture lysis in children [Letter]
Beck, A D; Lynch, M G; Noe, R; Brown, R H; Buzawa, D
PMID: 7864741
ISSN: 0003-9950
CID: 1736492
Clinicopathologic features of excised mitomycin filtering blebs [Case Report]
Hutchinson, A K; Grossniklaus, H E; Brown, R H; McManus, P E; Bradley, C K
Using light and electron microscopy, we examined two conjunctival filtering blebs that had been treated with mitomycin just prior to trabeculectomy and were later excised due to ocular hypotony. Light microscopy showed attenuated epithelium, loosely arranged subepithelial connective tissue, and scattered acute and chronic inflammatory cells. Electron microscopy also showed these findings and demonstrated the presence of presumably viable activated fibrocytes in the subepithelial connective tissue. The presence of inflammatory cells in the blebs was attributed to concurrent infections and suggests that mitomycin does not completely suppress, but may attenuate, the inflammatory response. The mechanism of hypotony and bleb failure in the two eyes was most likely a combination of over-filtration and a persistent wound leak due to a lack of postoperative subconjunctival fibrosis secondary to treatment with mitomycin.
PMID: 8285898
ISSN: 0003-9950
CID: 1736502
