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Johnson JO, Chia R, Miller DE, et al. Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis. JAMA Neurol. 2021;78(10):1236-1248doi: 10.1001/jamaneurol.2021.2598.
Johnson, J. O., Chia, R., Miller, D. E., Li, R., Kumaran, R., Abramzon, Y., Alahmady, N., Renton, A. E., Topp, S. D., Gibbs, J. R., Cookson, M. R., Sabir, M. S., Dalgard, C. L., Troakes, C., Jones, A. R., Shatunov, A., Iacoangeli, A., Al Khleifat, A., Ticozzi, N., Silani, V., Gellera, C., Blair, I. P., Dobson-Stone, C., Kwok, J. B., Bonkowski, E. S., Palvadeau, R., Tienari, P. J., Morrison, K. E., Shaw, P. J., Al-Chalabi, A., Brown, R. H., Calvo, A., Mora, G., Al-Saif, H., Gotkine, M., Leigh, F., Chang, I. J., Perlman, S. J., Glass, I., Scott, A. I., Shaw, C. E., Basak, A. N., Landers, J. E., Chiò, A., Crawford, T. O., Smith, B. N., Traynor, B. J., Smith, B. N., Ticozzi, N., Fallini, C., Gkazi, A. S., Topp, S. D., Scotter, E. L., Kenna, K. P., Keagle, P., Tiloca, C., Vance, C., Troakes, C., Colombrita, C., King, A., Pensato, V., Castellotti, B., Baas, F., Ten Asbroek, A. L. M. A., McKenna-Yasek, D., McLaughlin, R. L., Polak, M., Asress, S., Esteban-Pérez, J., Stevic, Z., D'Alfonso, S., Mazzini, L., Comi, G. P., 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. L., Nicholson, G. A., Blair, I. P., Leblond-Manry, C., Rouleau, G. A., Hardiman, O., Morrison, K. E., Veldink, J. H., van den Berg, L. H., Al-Chalabi, A., Pall, H., Shaw, P. J., Turner, M. R., Talbot, K., Taroni, F., García-Redondo, A., Wu, Z., Glass, J. D., Gellera, C., Ratti, A., Brown, R. H., Silani, V., Shaw, C. E., Landers, J. E., Dalgard, C. L., Adeleye, A., Soltis, A. R., Alba, C., Viollet, C., Bacikova, D., Hupalo, D. N., Sukumar, G., Pollard, H. B., Wilkerson, M. D., Martinez, E. M., Abramzon, Y., Ahmed, S., Arepalli, S., Baloh, R. H., Bowser, R., Brady, C. B., Brice, A., Broach, J., Campbell, R. H., Camu, W., Chia, R., Cooper-Knock, J., Ding, J., Drepper, C., Drory, V. E., Dunckley, T. L., Eicher, J. D., England, B. K., Faghri, F., Feldman, E., Floeter, M. K., Fratta, P., Geiger, J. T., Gerhard, G., Gibbs, J. R., Gibson, S. B., Glass, J. D., Hardy, J., Harms, M. B., Heiman-Patterson, T. D., Hernandez, D. G., Jansson, L., Kirby, J., Kowall, N. W., Laaksovirta, H., Landeck, N., Landi, F., Le Ber, I., Lumbroso, S., MacGowan, D. J. L., Maragakis, N. J., Mora, G., Mouzat, K., Murphy, N. A., Myllykangas, L., Nalls, M. A., Orrell, R. W., Ostrow, L. W., Pamphlett, R., Pickering-Brown, S., Pioro, E. P., Pletnikova, O., Pliner, H. A., Pulst, S. M., Ravits, J. M., Renton, A. E., Rivera, A., Robberecht, W., Rogaeva, E., Rollinson, S., Rothstein, J. D., Scholz, S. W., Sendtner, M., Shaw, P. J., Sidle, K. C., Simmons, Z., Singleton, A. B., Smith, N., Stone, D. J., Tienari, P. J., Troncoso, J. C., Valori, M., Van Damme, P., Van Deerlin, V. M., Van Den Bosch, L., Zinman, L., Landers, J. E., Chiò, A., Traynor, B. J., Angelocola, S. M., Ausiello, F. P., Barberis, M., Bartolomei, I., Battistini, S., Bersano, E., Bisogni, G., Borghero, G., Brunetti, M., Cabona, C., Calvo, A., Canale, F., Canosa, A., Cantisani, T. A., Capasso, M., Caponnetto, C., Cardinali, P., Carrera, P., Casale, F., Chiò, A., Colletti, T., Conforti, F. L., Conte, A., Conti, E., Corbo, M., Cuccu, S., Dalla Bella, E., D'Errico, E., DeMarco, G., Dubbioso, R., Ferrarese, C., Ferraro, P. M., 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., Lauria, G., Liguori, R., Logroscino, G., Logullo, F. O., Lunetta, C., Mandich, P., Mandrioli, J., Manera, U., Manganelli, F., Marangi, G., Marinou, K., Marrosu, M. G., Martinelli, I., Messina, S., Moglia, C., Mora, G., Mosca, L., Murru, M. R., 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. (2021). Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis. JAMA neurology, 78(10), 1236-1248. https://doi.org/10.1001/jamaneurol.2021.2598
Johnson, Janel O, et al. "Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis." JAMA neurology vol. 78,10 (2021): 1236-1248. doi: https://doi.org/10.1001/jamaneurol.2021.2598
Johnson JO, Chia R, Miller DE, Li R, Kumaran R, Abramzon Y, Alahmady N, Renton AE, Topp SD, Gibbs JR, Cookson MR, Sabir MS, Dalgard CL, Troakes C, Jones AR, Shatunov A, Iacoangeli A, Al Khleifat A, Ticozzi N, Silani V, Gellera C, Blair IP, Dobson-Stone C, Kwok JB, Bonkowski ES, Palvadeau R, Tienari PJ, Morrison KE, Shaw PJ, Al-Chalabi A, Brown RH, Calvo A, Mora G, Al-Saif H, Gotkine M, Leigh F, Chang IJ, Perlman SJ, Glass I, Scott AI, Shaw CE, Basak AN, Landers JE, Chiò A, Crawford TO, Smith BN, Traynor BJ, Smith BN, Ticozzi N, Fallini C, Gkazi AS, Topp SD, Scotter EL, Kenna KP, Keagle P, Tiloca C, Vance C, Troakes C, Colombrita C, King A, Pensato V, Castellotti B, Baas F, Ten Asbroek ALMA, McKenna-Yasek D, McLaughlin RL, Polak M, Asress S, Esteban-Pérez J, Stevic Z, D'Alfonso S, Mazzini L, Comi GP, 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 KL, Nicholson GA, Blair IP, Leblond-Manry C, Rouleau GA, Hardiman O, Morrison KE, Veldink JH, van den Berg LH, Al-Chalabi A, Pall H, Shaw PJ, Turner MR, Talbot K, Taroni F, García-Redondo A, Wu Z, Glass JD, Gellera C, Ratti A, Brown RH, Silani V, Shaw CE, Landers JE, Dalgard CL, Adeleye A, Soltis AR, Alba C, Viollet C, Bacikova D, Hupalo DN, Sukumar G, Pollard HB, Wilkerson MD, Martinez EM, Abramzon Y, Ahmed S, Arepalli S, Baloh RH, Bowser R, Brady CB, Brice A, Broach J, Campbell RH, Camu W, Chia R, Cooper-Knock J, Ding J, Drepper C, Drory VE, Dunckley TL, Eicher JD, England BK, Faghri F, Feldman E, Floeter MK, Fratta P, Geiger JT, Gerhard G, Gibbs JR, Gibson SB, Glass JD, Hardy J, Harms MB, Heiman-Patterson TD, Hernandez DG, Jansson L, Kirby J, Kowall NW, Laaksovirta H, Landeck N, Landi F, Le Ber I, Lumbroso S, MacGowan DJL, Maragakis NJ, Mora G, Mouzat K, Murphy NA, Myllykangas L, Nalls MA, Orrell RW, Ostrow LW, Pamphlett R, Pickering-Brown S, Pioro EP, Pletnikova O, Pliner HA, Pulst SM, Ravits JM, Renton AE, Rivera A, Robberecht W, Rogaeva E, Rollinson S, Rothstein JD, Scholz SW, Sendtner M, Shaw PJ, Sidle KC, Simmons Z, Singleton AB, Smith N, Stone DJ, Tienari PJ, Troncoso JC, Valori M, Van Damme P, Van Deerlin VM, Van Den Bosch L, Zinman L, Landers JE, Chiò A, Traynor BJ, Angelocola SM, Ausiello FP, Barberis M, Bartolomei I, Battistini S, Bersano E, Bisogni G, Borghero G, Brunetti M, Cabona C, Calvo A, Canale F, Canosa A, Cantisani TA, Capasso M, Caponnetto C, Cardinali P, Carrera P, Casale F, Chiò A, Colletti T, Conforti FL, Conte A, Conti E, Corbo M, Cuccu S, Dalla Bella E, D'Errico E, DeMarco G, Dubbioso R, Ferrarese C, Ferraro PM, 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, Lauria G, Liguori R, Logroscino G, Logullo FO, Lunetta C, Mandich P, Mandrioli J, Manera U, Manganelli F, Marangi G, Marinou K, Marrosu MG, Martinelli I, Messina S, Moglia C, Mora G, Mosca L, Murru MR, 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. Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis. JAMA Neurol. 2021 Oct 01;78(10):1236-1248. doi: 10.1001/jamaneurol.2021.2598. PMID: 34459874; PMCID: PMC8406220.
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JAMA Neurol. 2021 Oct 01;78(10):1236-1248. doi: 10.1001/jamaneurol.2021.2598.

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

JAMA neurology

Janel O Johnson, Ruth Chia, Danny E Miller, Rachel Li, Ravindran Kumaran, Yevgeniya Abramzon, Nada Alahmady, Alan E Renton, Simon D Topp, J Raphael Gibbs, Mark R Cookson, Marya S Sabir, Clifton L Dalgard, Claire Troakes, Ashley R Jones, Aleksey Shatunov, Alfredo Iacoangeli, Ahmad Al Khleifat, Nicola Ticozzi, Vincenzo Silani, Cinzia Gellera, Ian P Blair, Carol Dobson-Stone, John B Kwok, Emily S Bonkowski, Robin Palvadeau, Pentti J Tienari, Karen E Morrison, Pamela J Shaw, Ammar Al-Chalabi, Robert H Brown, Andrea Calvo, Gabriele Mora, Hind Al-Saif, Marc Gotkine, Fawn Leigh, Irene J Chang, Seth J Perlman, Ian Glass, Anna I Scott, Christopher E Shaw, A Nazli Basak, John E Landers, Adriano Chiò, Thomas O Crawford, Bradley N Smith, Bryan J Traynor, Bradley N Smith, Nicola Ticozzi, Claudia Fallini, Athina Soragia Gkazi, Simon D Topp, Emma L Scotter, Kevin P Kenna, Pamela Keagle, Cinzia Tiloca, Caroline Vance, Claire Troakes, Claudia Colombrita, Andrew King, Viviana Pensato, Barbara Castellotti, Frank Baas, Anneloor L M A Ten Asbroek, Diane McKenna-Yasek, Russell L McLaughlin, Meraida Polak, Seneshaw Asress, Jesús Esteban-Pérez, Zorica Stevic, Sandra D'Alfonso, Letizia Mazzini, Giacomo P Comi, Roberto Del Bo, Mauro Ceroni, Stella Gagliardi, Giorgia Querin, Cinzia Bertolin, Wouter van Rheenen, Rosa Rademakers, Marka van Blitterswijk, Giuseppe Lauria, Stefano Duga, Stefania Corti, Cristina Cereda, Lucia Corrado, Gianni Sorarù, Kelly L Williams, Garth A Nicholson, Ian P Blair, Claire Leblond-Manry, Guy A Rouleau, Orla Hardiman, Karen E Morrison, Jan H Veldink, Leonard H van den Berg, Ammar Al-Chalabi, Hardev Pall, Pamela J Shaw, Martin R Turner, Kevin Talbot, Franco Taroni, Alberto García-Redondo, Zheyang Wu, Jonathan D Glass, Cinzia Gellera, Antonia Ratti, Robert H Brown, Vincenzo Silani, Christopher E Shaw, John E Landers, Clifton L Dalgard, Adelani Adeleye, Anthony R Soltis, Camille Alba, Coralie Viollet, Dagmar Bacikova, Daniel N Hupalo, Gauthaman Sukumar, Harvey B Pollard, Matthew D Wilkerson, Elisa McGrath Martinez, Yevgeniya Abramzon, Sarah Ahmed, Sampath Arepalli, Robert H Baloh, Robert Bowser, Christopher B Brady, Alexis Brice, James Broach, Roy H Campbell, William Camu, Ruth Chia, John Cooper-Knock, Jinhui Ding, Carsten Drepper, Vivian E Drory, Travis L Dunckley, John D Eicher, Bryce K England, Faraz Faghri, Eva Feldman, Mary Kay Floeter, Pietro Fratta, Joshua T Geiger, Glenn Gerhard, J Raphael Gibbs, Summer B Gibson, Jonathan D Glass, John Hardy, Matthew B Harms, Terry D Heiman-Patterson, Dena G Hernandez, Lilja Jansson, Janine Kirby, Neil W Kowall, Hannu Laaksovirta, Natalie Landeck, Francesco Landi, Isabelle Le Ber, Serge Lumbroso, Daniel J L MacGowan, Nicholas J Maragakis, Gabriele Mora, Kevin Mouzat, Natalie A Murphy, Liisa Myllykangas, Mike A Nalls, Richard W Orrell, Lyle W Ostrow, Roger Pamphlett, Stuart Pickering-Brown, Erik P Pioro, Olga Pletnikova, Hannah A Pliner, Stefan M Pulst, John M Ravits, Alan E Renton, Alberto Rivera, Wim Robberecht, Ekaterina Rogaeva, Sara Rollinson, Jeffrey D Rothstein, Sonja W Scholz, Michael Sendtner, Pamela J Shaw, Katie C Sidle, Zachary Simmons, Andrew B Singleton, Nathan Smith, David J Stone, Pentti J Tienari, Juan C Troncoso, Miko Valori, Philip Van Damme, Vivianna M Van Deerlin, Ludo Van Den Bosch, Lorne Zinman, John E Landers, Adriano Chiò, Bryan J Traynor, Stefania M Angelocola, Francesco P Ausiello, Marco Barberis, Ilaria Bartolomei, Stefania Battistini, Enrica Bersano, Giulia Bisogni, Giuseppe Borghero, Maura Brunetti, Corrado Cabona, Andrea Calvo, Fabrizio Canale, Antonio Canosa, Teresa A Cantisani, Margherita Capasso, Claudia Caponnetto, Patrizio Cardinali, Paola Carrera, Federico Casale, Adriano Chiò, Tiziana Colletti, Francesca L Conforti, Amelia Conte, Elisa Conti, Massimo Corbo, Stefania Cuccu, Eleonora Dalla Bella, Eustachio D'Errico, Giovanni DeMarco, Raffaele Dubbioso, Carlo Ferrarese, Pilar M Ferraro, Massimo Filippi, Nicola Fini, Gianluca Floris, Giuseppe Fuda, Salvatore Gallone, Giulia Gianferrari, Fabio Giannini, Maurizio Grassano, Lucia Greco, Barbara Iazzolino, Alessandro Introna, Vincenzo La Bella, Serena Lattante, Giuseppe Lauria, Rocco Liguori, Giancarlo Logroscino, Francesco O Logullo, Christian Lunetta, Paola Mandich, Jessica Mandrioli, Umberto Manera, Fiore Manganelli, Giuseppe Marangi, Kalliopi Marinou, Maria Giovanna Marrosu, Ilaria Martinelli, Sonia Messina, Cristina Moglia, Gabriele Mora, Lorena Mosca, Maria R Murru, Paola Origone, Carla Passaniti, Cristina Petrelli, Antonio Petrucci, Susanna Pozzi, Maura Pugliatti, Angelo Quattrini, Claudia Ricci, Giulia Riolo, Nilo Riva, Massimo Russo, Mario Sabatelli, Paolina Salamone, Marco Salivetto, Fabrizio Salvi, Marialuisa Santarelli, Luca Sbaiz, Riccardo Sideri, Isabella Simone, Cecilia Simonini, Rossella Spataro, Raffaella Tanel, Gioacchino Tedeschi, Anna Ticca, Antonella Torriello, Stefania Tranquilli, Lucio Tremolizzo, Francesca Trojsi, Rosario Vasta, Veria Vacchiano, Giuseppe Vita, Paolo Volanti, Marcella Zollino, Elisabetta Zucchi

Affiliations

  1. Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
  2. Division of Medical Genetics, Department of Medicine, University of Washington, Seattle.
  3. Department of Pediatrics, Division of Genetic Medicine, Seattle Children's Hospital, University of Washington, Seattle.
  4. Department of Pediatrics, Children's Hospital of Richmond at VCU, Richmond, Virginia.
  5. Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
  6. Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.
  7. Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
  8. Department of Biology, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.
  9. Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York.
  10. Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, New York.
  11. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
  12. UK Dementia Research Institute at King's College London, London, United Kingdom.
  13. Computational Biology Group, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
  14. Neurodegenerative Diseases Research Unit, Laboratory of Neurogenetics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
  15. Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
  16. The American Genome Center, Collaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
  17. Istituto Auxologico Italiano, IRCCS, Department of Neurology-Stroke Unit and Laboratory of Neuroscience, Milan, Italy.
  18. Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milan, Italy.
  19. Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico 'Carlo Besta,' Milan, Italy.
  20. Centre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
  21. The University of Sydney, Brain and Mind Centre and School of Medical Sciences, Faculty of Medicine and Health, Camperdown, Australia.
  22. School of Medical Sciences, University of New South Wales, Kensington, Australia.
  23. Suna and Inan K?rac Foundation, Neurodegeneration Research Laboratory, KUTTAM, School of Medicine, Koc University, Istanbul, Turkey.
  24. Department of Neurology, Helsinki University Hospital and Translational Immunology Programme, Biomedicum, University of Helsinki, Helsinki, Finland.
  25. Faculty of Medicine, Health and Life Sciences, Queen's University Belfast, Belfast, United Kingdom.
  26. Sheffield Institute for Translational Neuroscience, Department of Neuroscience, University of Sheffield, Sheffield, United Kingdom.
  27. Department of Neurology, King's College Hospital, London, United Kingdom.
  28. Department of Neurology, University of Massachusetts Medical School, Worcester.
  29. ALS Center, 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy.
  30. ALS Center, ICS Maugeri, IRCCS, Milan, Italy.
  31. Department of Neurology, Children's Hospital of Richmond at VCU, Richmond, Virginia.
  32. Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
  33. Department of Neurology, Seattle Children's Hospital, University of Washington, Seattle.
  34. Department of Laboratories, Seattle Children's Hospital, Seattle, Washington.
  35. Department of Laboratory Medicine, University of Washington, Seattle.
  36. Neurology 1, AOU Città della Salute e della Scienza, Turin, Italy.
  37. Department of Neurology, Johns Hopkins University, Baltimore, Maryland.
  38. Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland.
  39. National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.
  40. Centre for Neurodegeneration Research, King's College London, Department of Clinical Neuroscience, Institute of Psychiatry, London, United Kingdom.
  41. Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy.
  42. Centre for Brain Research, University of Auckland, Auckland, New Zealand.
  43. Department of Neurology, IRCCS Istituto Auxologico Italiano, Milan, Italy.
  44. Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, United Kingdom.
  45. Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico 'Carlo Besta,' Milan, Italy.
  46. Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
  47. Department of Neurogenetics and Neurology, Academic Medical Centre, Amsterdam, the Netherlands.
  48. Population Genetics Laboratory, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Republic of Ireland.
  49. Department of Neurology, Emory University, Atlanta, Georgia.
  50. Unidad de ELA, Instituto de Investigación Hospital 12 de Octubre de Madrid, SERMAS, and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER U-723), Madrid, Spain.
  51. Neurology Clinic, Clinical Center of Serbia School of Medicine, University of Belgrade, Belgrade, Serbia.
  52. Department of Health Sciences, University of Eastern Piedmont, Novara, Italy.
  53. ALS Center, Azienda Ospedaliero Universitaria Maggiore della Carità, Novara, Italy.
  54. Neurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
  55. Department of Brain and Behavior, University of Pavia, Pavia, Italy.
  56. General Neurology Unit, IRCCS Mondino Foundation, Pavia, Italy.
  57. Genomic and Post-Genomic Center, Mondino Foundation-IRCCS, Pavia, Italy.
  58. Department of Neurosciences, University of Padova, Padova, Italy.
  59. Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
  60. Department of Neuroscience, Mayo Clinic, Jacksonville, Florida.
  61. 3rd Neurology Unit, Motor Neuron Diseases Center, Fondazione IRCCS Istituto Neurologico 'Carlo Besta,' Milan, Italy.
  62. Humanitas Clinical and Research Center-IRCCS, Milan, Italy.
  63. Department of Biomedical Sciences, Humanitas University, Milan, Italy.
  64. Molecular Medicine Laboratory, Clinical Sciences Building, Concord Hospital, Concord, Australia.
  65. Human Genetics and Cognitive Functions Unit, Institut Pasteur, Paris, France.
  66. Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
  67. Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Republic of Ireland.
  68. School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom.
  69. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
  70. Department of Bioinformatics and Computational Biology, Worcester Polytechnic Institute, Worcester, Massachusetts.
  71. Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland.
  72. Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland.
  73. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London, United Kingdom.
  74. Neurodegenerative Diseases Research Unit, Laboratory of Neurogenetics, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.
  75. Genomics Technology Group, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland.
  76. Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California.
  77. Division of Neurology, Barrow Neurological Institute, Phoenix, Arizona.
  78. Research and Development Service, Veterans Affairs Boston Healthcare System, Boston, Massachusetts.
  79. Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Université Pierre et Marie Curie, Paris, France.
  80. INSERM U975, Paris, France.
  81. Department of Biochemistry, Penn State College of Medicine, Hershey, Pennsylvania.
  82. Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana.
  83. ALS Reference Center, Gui de Chauliac Hospital, CHU and University of Montpellier, Montpellier, France.
  84. Department of Neuroscience, University of Sheffield, Sheffield, United Kingdom.
  85. Computational Biology Group, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland.
  86. Institute for Clinical Neurobiology, University of Würzburg, Würzburg, Germany.
  87. Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
  88. Neurodegenerative Disease Research Center, Biodesign Institute, Arizona State University, Tempe.
  89. Department of Genetics and Pharmacogenomics, Merck Research Laboratories, Merck, West Point, Pennsylvania.
  90. Human Genetics Branch, National Institute of Mental Health, Bethesda, Maryland.
  91. Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland.
  92. Department of Neurology, University of Michigan, Ann Arbor.
  93. Motor Neuron Disorders Unit, Laboratory of Neurogenetics, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.
  94. Department of Pathology, Penn State College of Medicine, Hershey, Pennsylvania.
  95. Department of Neurology, University of Utah School of Medicine, Salt Lake City.
  96. Department of Neurology, Emory University School of Medicine, Atlanta, Georgia.
  97. Department of Molecular Neuroscience and Reta Lila Weston Laboratories, Institute of Neurology, University College London, London, United Kingdom.
  98. Department of Neurology, Columbia University, New York, New York.
  99. Department of Neurology, Drexel University College of Medicine, Philadelphia, Pennsylvania.
  100. Department of Neurology, Temple University, Philadelphia, Pennsylvania.
  101. Department of Neurology, University of Helsinki, Helsinki, Finland.
  102. Department of Neurology, Veterans Affairs Boston Healthcare System, Boston, Massachusetts.
  103. Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland.
  104. Department of Geriatrics, Neurosciences and Orthopedics, Center for Geriatric Medicine, Catholic University of Sacred Heart, Rome, Italy.
  105. INM, INSERM, University of Montpellier, CHU Nîmes, Nîmes, France.
  106. Neuromuscular Division and ALS Center, Beth Israel Medical Center, Albert Einstein College of Medicine, New York, New York.
  107. Department of Pathology, Haartman Institute/HUSLAB, University of Helsinki and Folkhalsan Research Center (LM), Helsinki, Finland.
  108. Data Tecnica International, Glen Echo, Maryland.
  109. Department of Clinical Neuroscience, Institute of Neurology, University College London, London, United Kingdom.
  110. Discipline of Pathology, Brain and Mind Centre, University of Sydney, Camperdown, Australia.
  111. Faculty of Human and Medical Sciences, University of Manchester, Manchester, United Kingdom.
  112. Department of Neurology, Cleveland Clinic, Cleveland, Ohio.
  113. Clinical and Neuropathology Core, Johns Hopkins University, Baltimore, Maryland.
  114. Department of Neuroscience, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease, University of California San Diego, La Jolla.
  115. Nash Family Department of Neuroscience, Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, New York.
  116. Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium.
  117. Tanz Centre for Research of Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
  118. Department of Neurology, Institute for Clinical Neurobiology, University of Würzburg, Würzburg, Germany.
  119. Department of Neurology, Penn State College of Medicine, Hershey, Pennsylvania.
  120. VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, University of Leuven, Leuven, Belgium.
  121. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia.
  122. Division of Neurology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
  123. 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy.
  124. Neuroscience Institute of Torino, University of Turin, Turin, Italy.
  125. Neurology Unit, AV4 ASUR Marche, Fermo, Italy.
  126. Department of Medical Genetic, Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Torino, Italy.
  127. Center for Diagnosis and Cure of Rare Diseases, Department of Neurology, IRCCS Institute of Neurological Sciences, Bologna, Italy.
  128. Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy.
  129. 3rd Neurology Unit and Motor Neuron Diseases Centre, IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy.
  130. NeuroMuscular Omnicentre (NEMO), Serena Onlus, Foundation Pol. A. Gemelli, Roma, Italy.
  131. Neurologic Unit, Monserrato University Hospital, Cagliari University, Cagliari, Italy.
  132. Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal-Child Sciences, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  133. Division of Neurology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
  134. Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli," Caserta, Italy.
  135. Struttura complessa di Neurofisiopatologia, Azienda Ospedaliera di Perugia, Perugia, Italy.
  136. Unit of Neurology, Ospedale Clinicizzato SS Annunziata, Chieti, Italy.
  137. Unit of Genomics for the Diagnosis of Human Pathologies, IRCCS San Raffaele Scientific Institute, Milan, Italy.
  138. ALS Clinical Research Center, BiND, University of Palermo, Palermo, Italy.
  139. Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
  140. Neurology Unit, "San Gerardo" Hospital, Monza, Italy.
  141. School of Medicine and Surgery and Milan Center for Neuroscience (NeuroMI), University of Milano-Bicocca, Milan, Italy.
  142. Department of Neurorehabilitation Sciences, Casa Cura Policlinico, Milan, Italy.
  143. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro," Policlinic, Bari, Italy.
  144. Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Napoli, Italy.
  145. Neurology Unit and Rehabilitation Unit, IRCCS "San Raffaele Scientific Institute," Milan, Italy.
  146. Neuroimaging Research Unit, Division of Neuroscience, IRCCS "San Raffaele Scientific Institute," Milan, Italy.
  147. Neurophysiology Service, IRCCS "San Raffaele Scientific Institute," Milan, Italy.
  148. Vita-Salute San Raffaele University, Milan, Italy.
  149. Department of Neurosciences, Ospedale Civile S. Agostino Estense, Azienda Ospedaliero Universitaria di Modena, Modena, Italy.
  150. NeuroMuscular Omnicentre (NEMO) Clinical Center Milano, Fondazione Serena Onlus, Milan, Italy.
  151. Genetica Medica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.
  152. Dipartimento Universitario Scienze della Vita e Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Roma, Italy.
  153. Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, Milan, Italy.
  154. Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
  155. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
  156. Center for Neurodegenerative Diseases and the Aging Brain, Department of Clinical Research in Neurology, Pia Fondazione Cardinale G. Panico, Tricase, Italy.
  157. Neurology Unit, AV3, ASUR Marche, Macerata, Italy.
  158. Medical Genetics Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  159. Department of Neurorehabilitation, Istituti Clinici Scientifici Maugeri IRCCS, Institute of Milan, Milan, Italy.
  160. Department of Neurology, Azienda Universitario Ospedaliera di Cagliari and University of Cagliari, Cagliari, Italy.
  161. NeuroMuscular Omnicentre (NEMO) Sud, Fondazione Aurora, OUC Neurology and Neuromuscular Disorders, University of Messina, Messina, Italy.
  162. Department of Laboratory Medicine, Medical Genetics, Niguarda Ca' Granda Hospital, Milan, Italy.
  163. Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli," Napoli, Italy.
  164. Neurology Department, San Camillo Hospital, Roma, Italy.
  165. Department of Biomedical and Surgical Sciences, Section of Neurological, Psychiatric and Psychological Sciences, University of Ferrara, Ferrara, Italy.
  166. Department of Neurology, IRCCS "San Raffaele Scientific Institute," Milan, Italy.
  167. OUC Neurology and Neuromuscular Disorders, University of Messina, Messina, Italy.
  168. NeuroMuscular Omnicentre (NEMO)-Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Roma, Italy.
  169. Department of Medicine, Azienda Complesso Ospedaliero, San Filippo Neri, Roma, Italy.
  170. Operative Unit of Neurology, S. Chiara Hospital, Trento, Italy.
  171. Department of Neurology, Azienda Ospedaliera San Francesco, Nuoro, Italy.
  172. ALS Center, Operative Unit of Neurology, AOU "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy.
  173. Neurorehabilitation Unit-ALS Center, Istituti Clinici Scientifici (ICS) Maugeri, Mistretta, Italy.
  174. Sezione di Medicina Genomica, Dipartimento Scienze della Vita e Sanità Pubblica, Facoltà di Medicina e Chirurgia, Università Cattolica Sacro Cuore, Roma, Italy.
  175. Unità di Genetica Medica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.

PMID: 34459874 PMCID: PMC8406220 DOI: 10.1001/jamaneurol.2021.2598

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 pathway.

CONCLUSIONS AND RELEVANCE: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.

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