Murdoch University Research Repository

Welcome to the Murdoch University Research Repository

The Murdoch University Research Repository is an open access digital collection of research
created by Murdoch University staff, researchers and postgraduate students.

Learn more

SQSTM1 and VCP mutations in a series of 205 inclusion body myositis cases

Gang, Q., Bettencourt, C., Brady, S., Holton, J.L., Pittman, A.M., Hughes, D., Healy, E., Parton, M., Hilton-Jones, D., Shieh, P.B., Needham, M., Liang, C., Zanoteli, E., de Carmargo, L.V., De Paepe, B., De Bleecker, J., Shaibani, A., Ripolone, M., Violano, R., Moggio, M., Barohn, R.J., Dimachkie, M.M., Mora, M., Mantegazza, R., Zanotti, S., Singleton, A.B., Hanna, M.G., Houlden, H. and Machado, P.M. (2015) SQSTM1 and VCP mutations in a series of 205 inclusion body myositis cases. In: Muscle Study Group Meeting on Experimental Therapeutics Across the Spectrum of Neuromuscular Disease, 19 - 21 September 2015, Snowbird, UT, USA

Link to Published Version: http://dx.doi.org/10.1002/mus.24792
*Subscription may be required

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.

Item Type: Conference Paper
Conference Website: http://musclestudygroup.org/
URI: http://researchrepository.murdoch.edu.au/id/eprint/34729
Item Control Page Item Control Page