CCNF mutations in amyotrophic lateral sclerosis and frontotemporal dementia Williams, KL, Topp, S, Yang, S, Smith, B, Fifita, JA, Warraich, ST, Zhang, KY, Farrawell, N, Vance, C, Hu, X, Chesi, A, Leblond, CS, Lee, A, Rayner, SL, Sundaramoorthy, V, Dobson-Stone, C, Molloy, MP, Van Blitterswijk, M, Dickson, DW, Petersen, RC, Graff-Radford, NR, Boeve, BF, Murray, ME, Pottier, C, Don, E, Winnick, C, McCann, EP, Hogan, A, Daoud, H, Levert, A, Dion, PA, Mitsui, J, Ishiura, H, Takahashi, Y, Goto, J, Kost, J, Gellera, C, Gkazi, AS, Miller, J, Stockton, J, Brooks, WS, Boundy, K, Polak, M, Muñoz-Blanco, JL, Esteban-Pérez, J, Rábano, A, Hardiman, O, Morrison, KE, Ticozzi, N, Silani, V, De Belleroche, J, Glass, JD, Kwok, JBJ, Guillemin, GJ, Chung, RS, Tsuji, S, Brown, RH, García-Redondo, A, Rademakers, R, Landers, JE, Gitler, AD, Rouleau, GA, Cole, NJ, Yerbury, JJ, Atkin, JD, Shaw, CE, Nicholson, GA and Blair, IP 2016, CCNF mutations in amyotrophic lateral sclerosis and frontotemporal dementia, Nature Communications, vol. 7, pp. 1-8, doi: 10.1038/ncomms11253. Attached Files Name Description MIMEType Size Downloads sundaramoorthy-ccnfmutations-2016.pdf Published version application/pdf 709.25KB 6 Title CCNF mutations in amyotrophic lateral sclerosis and frontotemporal dementia Author(s) Williams, KL Topp, S Yang, S Smith, B Fifita, JA Warraich, ST Zhang, KY Farrawell, N Vance, C Hu, X Chesi, A Leblond, CS Lee, A Rayner, SL Sundaramoorthy, V orcid.org/0000-0001-6309-8031 Dobson-Stone, C Molloy, MP Van Blitterswijk, M Dickson, DW Petersen, RC Graff-Radford, NR Boeve, BF Murray, ME Pottier, C Don, E Winnick, C McCann, EP Hogan, A Daoud, H Levert, A Dion, PA Mitsui, J Ishiura, H Takahashi, Y Goto, J Kost, J Gellera, C Gkazi, AS Miller, J Stockton, J Brooks, WS Boundy, K Polak, M Muñoz-Blanco, JL Esteban-Pérez, J Rábano, A Hardiman, O Morrison, KE Ticozzi, N Silani, V De Belleroche, J Glass, JD Kwok, JBJ Guillemin, GJ Chung, RS Tsuji, S Brown, RH García-Redondo, A Rademakers, R Landers, JE Gitler, AD Rouleau, GA Cole, NJ Yerbury, JJ Atkin, JD Shaw, CE Nicholson, GA Blair, IP Journal name Nature Communications Volume number 7 Article ID 11253 Start page 1 End page 8 Total pages 8 Publisher Nature Research Place of publication Berlin, Germany Publication date 2016-04-15 ISSN 2041-1723 Keyword(s) Amyotrophic lateral sclerosis Dementia Disease genetics Intracellular signalling peptides and proteins Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics UBIQUITIN-PROTEASOME SYSTEM LOBAR DEGENERATION PROTEIN ALS GENE FRAMEWORK STRESS TDP-43 RNA Summary Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping, fatal neurodegenerative disorders in which the molecular and pathogenic basis remains poorly understood. Ubiquitinated protein aggregates, of which TDP-43 is a major component, are a characteristic pathological feature of most ALS and FTD patients. Here we use genome-wide linkage analysis in a large ALS/FTD kindred to identify a novel disease locus on chromosome 16p13.3. Whole-exome sequencing identified a CCNF missense mutation at this locus. Interrogation of international cohorts identified additional novel CCNF variants in familial and sporadic ALS and FTD. Enrichment of rare protein-altering CCNF variants was evident in a large sporadic ALS replication cohort. CCNF encodes cyclin F, a component of an E3 ubiquitin-protein ligase complex (SCFCyclin F). Expression of mutant CCNF in neuronal cells caused abnormal ubiquitination and accumulation of ubiquitinated proteins, including TDP-43 and a SCFCyclin F substrate. This implicates common mechanisms, linked to protein homeostasis, underlying neuronal degeneration. Language eng DOI 10.1038/ncomms11253 Indigenous content off HERDC Research category C1 Refereed article in a scholarly journal Copyright notice ©2020, The Author(s) Free to Read? Yes Use Rights Persistent URL http://hdl.handle.net/10536/DRO/DU:30136663 Document type: Journal Article Collections: Faculty of Health School of Medicine Open Access Collection Related Links Link Description Link to full-text (open access)     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au. Versions Version Filter Type Mon, 11 May 2020, 12:40:21 EST Tue, 12 May 2020, 05:02:13 EST Tue, 12 May 2020, 08:06:26 EST Sat, 13 Jun 2020, 02:32:47 EST Sat, 16 Jan 2021, 05:06:51 EST Mon, 08 Feb 2021, 14:44:04 EST Mon, 08 Feb 2021, 14:46:28 EST Filtered Full Citation counts:   Cited 0 times in TR Web of Science Cited 96 times in Scopus Search Google Scholar Access Statistics: 9 Abstract Views, 6 File Downloads  -  Detailed Statistics Created: Mon, 11 May 2020, 12:40:21 EST

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