Conference paper
SQSTM1 and VCP mutations in a series of 205 inclusion body myositis cases
Muscle Study Group Meeting on Experimental Therapeutics Across the Spectrum of Neuromuscular Disease (Snowbird, UT, USA, 19/09/2015–21/09/2015)
2015
Abstract
Introduction: Clinico-pathologically overlapping inherited dis- orders indicate that genetic factors might be involved in sporadic inclusion body myositis (IBM) pathogenesis. Objectives: To identify genetic risk factors associated with IBM.
Methods: Whole-exome sequencing was performed in 205 IBM patients. Muscle tissue was pathologically evaluated and whole- transcriptome expression profiles generated.
Results: We identified eight rare missense mutations in the SQSTM1 and VCP genes in 10 IBM patients (5%). Five of the mutations had been previously reported in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) with Paget’s disease of bone (PDB); p62 staining was increased and MHC-I was up-regulated in the muscle tissue of these patients,
Conclusions: Variants in SQSTM1 and VCP may constitute genetic susceptibility factors for IBM. The occurrence of mutations in SQSTM1 and VCP in IBM, ALS, FTD and PDB rein- forces the link between these disorders, pinpointing converging pathogenic pathways resulting in impaired autophagy-lysosome processing, causing dysregulation of protein homeostasis.
Details
- Title
- SQSTM1 and VCP mutations in a series of 205 inclusion body myositis cases
- Authors/Creators
- Q. Gang (Author/Creator)C. Bettencourt (Author/Creator)S. Brady (Author/Creator)J.L. Holton (Author/Creator)A.M. Pittman (Author/Creator)D. Hughes (Author/Creator)E. Healy (Author/Creator)M. Parton (Author/Creator)D. Hilton-Jones (Author/Creator)P.B. Shieh (Author/Creator)M. Needham (Author/Creator)C. Liang (Author/Creator)E. Zanoteli (Author/Creator)L.V. de Carmargo (Author/Creator)B. De Paepe (Author/Creator)J. De Bleecker (Author/Creator)A. Shaibani (Author/Creator)M. Ripolone (Author/Creator)R. Violano (Author/Creator)M. Moggio (Author/Creator)R.J. Barohn (Author/Creator)M.M. Dimachkie (Author/Creator)M. Mora (Author/Creator)R. Mantegazza (Author/Creator)S. Zanotti (Author/Creator)A.B. Singleton (Author/Creator)M.G. Hanna (Author/Creator)H. Houlden (Author/Creator)P.M. Machado (Author/Creator)
- Conference
- Muscle Study Group Meeting on Experimental Therapeutics Across the Spectrum of Neuromuscular Disease (Snowbird, UT, USA, 19/09/2015–21/09/2015)
- Identifiers
- 991005543059407891
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Conference paper
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