Abstract
Purpose of reviewTo review the advances in our understanding of the genetics of inclusion body myositis (IBM) in the past year.Recent findingsOne large genetic association study focusing on immune-related genes in IBM has refined the association within the human leukocyte antigen (HLA) region to HLA-DRB1 alleles, and identified certain amino acid positions in HLA-DRB1 that may explain this risk. A suggestive association with CCR5 may indicate genetic overlap with other autoimmune diseases. Sequencing studies of candidate genes involved in related neuromuscular or neurodegenerative diseases have identified rare variants in VCP and SQSTM1. Proteomic studies of rimmed vacuoles in IBM and subsequent genetic analyses of candidate genes identified rare missense variants in FYCO1. Complex, large-scale mitochondrial deletions in cytochrome c oxidase-deficient muscle fibres expand our understanding of mitochondrial abnormalities in IBM.SummaryThe pathogenesis of IBM is likely multifactorial, including inflammatory and degenerative changes, and mitochondrial abnormalities. There has been considerable progress in our understanding of the genetic architecture of IBM, using complementary genetic approaches to investigate these different pathways.
Highlights
Sporadic inclusion body myositis (IBM) is the most common acquired muscle disease presenting in people over 50 years of age
A recent study used whole exome sequencing (WES) in 181 IBM patients focusing on p62, named sequestosome 1 (SQSTM1), and valosin-containing protein gene (VCP) genes, both of which are known to harbour genetic variants associated with amyotrophic lateral sclerosis (ALS), Paget’s disease of the bone (PDB) and frontotemporal dementia (FTD) [31&&]
As SQSTM1 is involved in the autophagy pathway, and VCP is involved in proteasomal degradation of misfolded proteins, this further supports the role of autophagic alterations and aggregation of proteins in the pathogenesis of IBM
Summary
Sporadic inclusion body myositis (IBM) is the most common acquired muscle disease presenting in people over 50 years of age. The primary cause of IBM remains unknown, genetic factors likely influence disease aCentre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, bGreater Manchester Neurosciences Centre, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, Stott Lane, Salford and cCentre for Epidemiology, Division of Population Health, Health Services Research and Primary Care, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
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