Journal article
Rare variants in SQSTM1 and VCP genes and risk of sporadic inclusion body myositis
Neurobiology of Aging, Vol.47, pp.e1-e9
2016
Abstract
Genetic factors have been suggested to be involved in the pathogenesis of sporadic inclusion body myositis (sIBM). SQSTM1 and VCP are two key genes associated with several neurodegenerative disorders but have yet to be thoroughly investigated in sIBM. A candidate gene analysis was conducted using whole-exome sequencing data from 181 sIBM patients, and whole-transcriptome expression analysis was performed in patients with genetic variants of interest. We identified six rare missense variants in the SQSTM1 and VCP in seven sIBM patients (4.0%). Two variants SQSTM1 p.G194R and the VCP p.R159C were significantly overrepresented in this sIBM cohort compared with controls. Five of these variants had been previously reported in patients with degenerative diseases. The mRNA levels of MHC genes were up-regulated, this elevation being more pronounced in SQSTM1 patient group. We report for the first time potentially pathogenic SQSTM1 variants and expand the spectrum of VCP variants in sIBM. These data suggests that defects in neurodegenerative pathways may confer genetic susceptibility to sIBM and reinforce the mechanistic overlap in these neurodegenerative disorders.
Details
- Title
- Rare variants in SQSTM1 and VCP genes and risk of sporadic inclusion body myositis
- Authors/Creators
- Q. Gang (Author/Creator) - University College LondonC. Bettencourt (Author/Creator) - University College LondonP.M. Machado (Author/Creator) - University College LondonS. Brady (Author/Creator) - University College LondonJ.L. Holton (Author/Creator) - University College LondonA.M. Pittman (Author/Creator) - University College LondonD. Hughes (Author/Creator) - University College LondonE. Healy (Author/Creator) - University College LondonM. Parton (Author/Creator) - University College LondonD. Hilton-Jones (Author/Creator) - John Radcliffe HospitalP.B. Shieh (Author/Creator) - University of California, Los AngelesM. Needham (Author/Creator) - The University of Western AustraliaC. Liang (Author/Creator) - Royal North Shore HospitalE. Zanoteli (Author/Creator) - Universidade de São PauloL.V. de Camargo (Author/Creator) - Universidade de São PauloB. De Paepe (Author/Creator) - Ghent University HospitalJ. De Bleecker (Author/Creator) - Ghent University HospitalA. Shaibani (Author/Creator)M. Ripolone (Author/Creator) - University of MilanR. Violano (Author/Creator) - University of MilanM. Moggio (Author/Creator) - University of MilanR.J. Barohn (Author/Creator) - University of KansasM.M. Dimachkie (Author/Creator) - University of KansasM. Mora (Author/Creator)R. Mantegazza (Author/Creator)S. Zanotti (Author/Creator)A.B. Singleton (Author/Creator) - National Institutes of HealthM.G. Hanna (Author/Creator) - University College LondonH. Houlden (Author/Creator) - University College London
- Publication Details
- Neurobiology of Aging, Vol.47, pp.e1-e9
- Publisher
- Elsevier Inc
- Identifiers
- 991005540369707891
- Copyright
- 2016 The Authors
- Murdoch Affiliation
- School of Health Professions
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.106 Rheumatology
- 1.106.1684 Dermatomyositis
- Web Of Science research areas
- Geriatrics & Gerontology
- Neurosciences
- ESI research areas
- Neuroscience & Behavior