Genetics of inclusion‐body myositis

  title={Genetics of inclusion‐body myositis},
  author={Merrilee Needham and Frank L Mastaglia and Michael J. Garlepp},
  journal={Muscle \& Nerve},
Sporadic inclusion‐body myositis (sIBM) is the most common acquired muscle disease in Caucasians over the age of 50 years. Pathologically it is marked by inflammatory, degenerative, and mitochondrial changes that interact in a yet‐unknown way to cause progressive muscle degeneration and weakness. The cause of the disease is unknown, but it is thought to involve a complex interplay between environmental factors, genetic susceptibility, and aging. The strongest evidence for genetic susceptibility… 
Sporadic inclusion body myositis: the genetic contributions to the pathogenesis
This review summarizes the current understanding of the genetic contributions to sIBM and provides some insights for future research in this mysterious disease with the advantage of the rapid development of advanced genetic technology.
Sporadic inclusion body myositis: variability in prevalence and phenotype and influence of the MHC.
  • F. Mastaglia
  • Biology, Medicine
    Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology
  • 2009
Recent observations indicate that the clinical phenotype at presentation is also quite variable and that the influence of the MHC is more complex than previously appreciated with HLA alleles also having modifying effects on the age-at-onset, severity and rate of progression of the disease.
Investigating novel therapeutic approaches for sporadic inclusion body myositis (sIBM)
The results of this Thesis show that β-APP over-expression in vitro recapitulates many of the characteristic features of sIBM and can be used successfully to screen potential therapies.
Genetic advances in sporadic inclusion body myositis
Advances in the genetics of sIBM over the past 2 years facilitated by the use of next-generation sequencing will be key tools to unravel the genetics and its contribution to disease aetiopathogenesis.
Genetics in inclusion body myositis
The pathogenesis of IBM is likely multifactorial, including inflammatory and degenerative changes, and mitochondrial abnormalities, and there has been considerable progress in understanding of the genetic architecture of IBM, using complementary genetic approaches to investigate these different pathways.
Advances in inclusion body myositis: genetics, pathogenesis and clinical aspects
Understanding the aetiopathogeneis is vital to identify future treatment targets, and understanding the natural history and the roles of biomarkers including the anti-CN1a antibody is vital for designing future clinical trials in IBM.
Genetic Investigations of Sporadic Inclusion Body Myositis and Myopathies with Structural Abnormalities and Protein Aggregates in Muscle
The collection of a large series of sIBM patients through the IIBMGC has been shown here to reveal important genetic findings and will be a valuable resource for the future.
Increase in number of sporadic inclusion body myositis (sIBM) in Japan
A retrospective survey of Japanese patients of sIBM diagnosed at the National Center of Neurology and Psychiatry (NCNP) finds that the prevalence of s IBM in Japan is 9.83 per million in 2003, suggesting an increase in the number of patients.


Sporadic inclusion body myositis—diagnosis, pathogenesis and therapeutic strategies
  • M. Dalakas
  • Biology, Medicine
    Nature Clinical Practice Neurology
  • 2006
Emerging data imply that continuous upregulation of cytokines and major histocompatibility complex class I on the muscle fibers causes an endoplasmic reticulum stress response, resulting in intracellular accumulation of misfolded glycoproteins and activation of the transcription factor NFκB, leading to further cytokine activation.
Hereditary inclusion body myopathy maps to chromosome 9p1-q1.
Genomewide linkage analyses identified the recessive IBM locus on chromosome 9 band p1-q1 (maximum lod score at D9S166 = 5.32, theta = 0.0) as the Friedreich's Ataxia gene, raising the possibility that HIBM may be a related neurogenic disorder.
Familial inflammatory inclusion body myositis.
Sporadic and familial inflammatory IBM share the same clinical, biological, MRI, and histological features.
Inclusion-body myositis
It is proposed that the identified abnormal accumulation, misfolding, and aggregation of proteins, perhaps provoked by the aging milieu and aggravated by the oxidative stress, lead to the s-IBM-specific vacuolar degeneration and atrophy of muscle fibers.
Molecular pathology and pathogenesis of inclusion‐body myositis
The basic hypothesis is that overexpression of AβPP within the aging muscle fibers is an early upstream event causing a subsequent pathogenic cascade that leads to sporadic inclusion‐body myositis.
Mutations spectrum of GNE in hereditary inclusion body myopathy sparing the quadriceps
This study brings to 17 the number of reported GNE mutations in quadriceps sparing myopathy, occurring either in the epimerase or the kinase domain of the enzyme, which is particularly common in Middle Eastern Jews.
Apolipoprotein E ϵ4 in inclusion body myositis
The frequency of the ϵ4 allele of apolipoprotein E (APO E) has been strongly associated with familial and late‐onset AD and data suggest that APO E genotype may be one of the factors involved in determining the predisposition to the development of IBM.
HLA associations with inclusion body myositis
The phenotype and phenotype data provide support for an autoimmune etiology for, and genetic predisposition to, IBM.
Inclusion body myositis and myopathies
Inclusion‐Body Myositis: Newest Concepts of Pathogenesis and Relation to Aging and Alzheimer Disease
  • W. Engel
  • Biology
    Journal of neuropathology and experimental neurology
  • 2001
Evidence is provided supporting the hypothesis that overexpression of AβPP within the aging muscle fibers is an early upstream event causing the subsequent pathogenic cascade, and the remarkable pathologic similarities between s-IBM muscle and Alzheimer disease (AD) brain are discussed.