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Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis
Authors :
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 Zucchi, Elisabetta
Publication Year :
2021
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
Details
Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1308940230
Document Type :
Electronic Resource