• Login
    View Item 
    •   Home
    • UMass Chan Faculty and Staff Research and Publications
    • UMass Chan Faculty and Researcher Publications
    • View Item
    •   Home
    • UMass Chan Faculty and Staff Research and Publications
    • UMass Chan Faculty and Researcher Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of eScholarship@UMassChanCommunitiesPublication DateAuthorsUMass Chan AffiliationsTitlesDocument TypesKeywordsThis CollectionPublication DateAuthorsUMass Chan AffiliationsTitlesDocument TypesKeywords

    My Account

    LoginRegister

    Help

    AboutSubmission GuidelinesData Deposit PolicySearchingAccessibilityTerms of UseWebsite Migration FAQ

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

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

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    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
    Smith, Bradley N
    Ticozzi, Nicola
    Fallini, Claudia
    Gkazi, Athina Soragia
    Topp, Simon D
    Scotter, Emma L
    Kenna, Kevin P
    Keagle, Pamela
    Tiloca, Cinzia
    Vance, Caroline
    Troakes, Claire
    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
    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
    García-Redondo, Alberto
    Wu, Zheyang
    Glass, Jonathan D
    Gellera, Cinzia
    Ratti, Antonia
    Brown, Robert H
    Silani, Vincenzo
    Shaw, Christopher E
    Landers, John E
    Dalgard, Clifton L
    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
    Abramzon, Yevgeniya
    Ahmed, Sarah
    Arepalli, Sampath
    Baloh, Robert H
    Bowser, Robert
    Brady, Christopher B
    Brice, Alexis
    Broach, James
    Campbell, Roy H
    Camu, William
    Chia, Ruth
    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
    Gibbs, J Raphael
    Gibson, Summer B
    Glass, Jonathan D
    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
    Mora, Gabriele
    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
    Renton, Alan E
    Rivera, Alberto
    Robberecht, Wim
    Rogaeva, Ekaterina
    Rollinson, Sara
    Rothstein, Jeffrey D
    Scholz, Sonja W
    Sendtner, Michael
    Shaw, Pamela J
    Sidle, Katie C
    Simmons, Zachary
    Singleton, Andrew B
    Smith, Nathan
    Stone, David J
    Tienari, Pentti J
    Troncoso, Juan C
    Valori, Miko
    Van Damme, Philip
    Van Deerlin, Vivianna M
    Van Den Bosch, Ludo
    Zinman, Lorne
    Landers, John E
    Chiò, Adriano
    Traynor, Bryan J
    Angelocola, Stefania M
    Ausiello, Francesco P
    Barberis, Marco
    Bartolomei, Ilaria
    Battistini, Stefania
    Bersano, Enrica
    Bisogni, Giulia
    Borghero, Giuseppe
    Brunetti, Maura
    Cabona, Corrado
    Calvo, Andrea
    Canale, Fabrizio
    Canosa, Antonio
    Cantisani, Teresa A
    Capasso, Margherita
    Caponnetto, Claudia
    Cardinali, Patrizio
    Carrera, Paola
    Casale, Federico
    Chiò, Adriano
    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
    Lauria, Giuseppe
    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
    Mora, Gabriele
    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
    Show allShow less
    UMass Chan Affiliations
    Neurology
    Document Type
    Journal Article
    Publication Date
    2021-08-30
    
    Metadata
    Show full item record
    Link to Full Text
    https://doi.org/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.
    Source
    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 Jr, 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; FALS Sequencing Consortium; American Genome Center; International ALS Genomics Consortium; and ITALSGEN Consortium; 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 Jr, 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 1;78(10):1236-1248. doi: 10.1001/jamaneurol.2021.2598. PMID: 34459874; PMCID: PMC8406220.
    DOI
    10.1001/jamaneurol.2021.2598
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/51663
    PubMed ID
    34459874
    ae974a485f413a2113503eed53cd6c53
    10.1001/jamaneurol.2021.2598
    Scopus Count
    Collections
    UMass Chan Faculty and Researcher Publications

    entitlement

    Related items

    Showing items related by title, author, creator and subject.

    • Thumbnail

      Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

      Van Rheenen, Wouter; van der Spek, Rick A A; Bakker, Mark K; van Vugt, Joke J F A; Hop, Paul J; Zwamborn, Ramona A J; de Klein, Niek; Westra, Harm-Jan; Bakker, Olivier B; Deelen, Patrick; et al. (2021-12-06)
      Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
    • Thumbnail

      SRSF2 promotes splicing and transcription of exon 11 included isoform in Ron proto-oncogene

      Moon, Heegyum; Cho, Sunghee; Loh, Tiing Jen; Oh, Hyun Kyung; Jang, Ha Na; Zhou, Jianhua; Kwon, Young-Soo; Liao, D. Joshua; Jun, Youngsoo; Eom, Soohyun; et al. (2014-09-08)
      The product of proto-oncogene Ron is a human receptor for the macrophage-stimulating protein (MSP). Upon activation, Ron is able to induce cell dissociation, migration and matrix invasion. Exon 11 skipping of Ron pre-mRNA produces Ron△165 protein that is constitutively active even in the absence of its ligand. Here we show that knockdown of SRSF2 promotes the decrease of exon 11 inclusion, whereas overexpression of SRSF2 promotes exon 11 inclusion. We demonstrate that SRSF2 promotes exon 11 inclusion through splicing and transcription procedure. We also present evidence that reduced expression of SRSF2 induces a decrease in the splicing of both introns 10 and 11; by contrast, overexpression of SRSF2 induces an increase in the splicing of introns 10 and 11. Through mutation analysis, we show that SRSF2 functionally targets and physically interacts with CGAG sequence on exon 11. In addition, we reveal that the weak strength of splice sites of exon 11 is not required for the function of SRSF2 on the splicing of Ron exon 11. Our results indicate that SRSF2 promotes exon 11 inclusion of Ron proto-oncogene through targeting exon 11. Our study provides a novel mechanism by which Ron is expressed.
    • Thumbnail

      Bi-allelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss

      Richard, Elodie M.; Bakhtiari, Somayeh; Marsh, Ashley P. L; Kaiyrzhanov, Rauan; Wagner, Matias; Shetty, Sheetal; Pagnozzi, Alex; Nordlie, Sandra M.; Guida, Brandon S.; Cornejo, Patricia; et al. (2021-10-10)
      Spermatogenesis-associated 5 like 1 (SPATA5L1) represents an orphan gene encoding a protein of unknown function. We report 28 bi-allelic variants in SPATA5L1 associated with sensorineural hearing loss in 47 individuals from 28 (26 unrelated) families. In addition, 25/47 affected individuals (53%) presented with microcephaly, developmental delay/intellectual disability, cerebral palsy, and/or epilepsy. Modeling indicated damaging effect of variants on the protein, largely via destabilizing effects on protein domains. Brain imaging revealed diminished cerebral volume, thin corpus callosum, and periventricular leukomalacia, and quantitative volumetry demonstrated significantly diminished white matter volumes in several individuals. Immunofluorescent imaging in rat hippocampal neurons revealed localization of Spata5l1 in neuronal and glial cell nuclei and more prominent expression in neurons. In the rodent inner ear, Spata5l1 is expressed in the neurosensory hair cells and inner ear supporting cells. Transcriptomic analysis performed with fibroblasts from affected individuals was able to distinguish affected from controls by principal components. Analysis of differentially expressed genes and networks suggested a role for SPATA5L1 in cell surface adhesion receptor function, intracellular focal adhesions, and DNA replication and mitosis. Collectively, our results indicate that bi-allelic SPATA5L1 variants lead to a human disease characterized by sensorineural hearing loss (SNHL) with or without a nonprogressive mixed neurodevelopmental phenotype.
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Lamar Soutter Library, UMass Chan Medical School | 55 Lake Avenue North | Worcester, MA 01655 USA
    Quick Guide | escholarship@umassmed.edu
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.