Sporadic inclusion body myositis: the genetic contributions to the pathogenesis

Abstract

Sporadic inclusion body myositis (sIBM) is the commonest idiopathic inflammatory muscle disease in people over 50 years old. It is characterized by slowly progressive muscle weakness and atrophy, with typical pathological changes of inflammation, degeneration and mitochondrial abnormality in affected muscle fibres. The cause(s) of sIBM are still unknown, but are considered complex, with the contribution of multiple factors such as environmental triggers, ageing and genetic susceptibility. 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. An international sIBM genetic study is ongoing and whole-exome sequencing will be applied in a large cohort of sIBM patients with the aim of unravelling important genetic risk factors for sIBM.

Sporadic inclusion body myositis: clinical, pathological, and genetic analysis of eight Polish patients

“…However, the precise role of TDP-43 accumulation is still unknown; it may cause neuronal dysfunction and disturb transcriptional regulation and RNA processing. We detected no TARDBP mutation associated with IBM, which is consistent with Qian Gang et al's study (Qian Gang et al, 2014) [9]. We did not detect pathogenic hexanucleotide expansion in C9ORF72, which is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) with TDP-43 inclusions (Weihl et al, 2015) [18].…”

Mitochondrial DNA disturbances and deregulated expression of oxidative phosphorylation and mitochondrial fusion proteins in sporadic inclusion body myositis

“…It has been proposed that its development could be due to a complex interaction of environmental agents, accelerated ageing and genetic susceptibility [2,17]. As muscle tissue has a high dependence on ATP to exert its function, mitochondrial alterations in sIBM could be one of the factors involved in triggering muscle weakness and degeneration, because these alterations have been related to muscle disease by many authors [18][19][20].…”

Sporadic Inclusion Body Myositis

“…MRG'nin tanıda rolünün artması ve sitozolik 5'nükleotidaz 1A otoantikorlarının saptanması erken tanıya yardımcı olabilecek unsurlardır. 3,4,6,7 sICM'nin nadiren multipl skleroz, konnektif doku hastalıkları, romatoid artrit, otoimmün tiroidit ve immünomediated trombositopenik purpura ile birlikteliği rapor edilmiştir. 8 sICM'nin etiyopatogenezinde genetik yatkın-lık, çevresel tetikleyiciler ve yaşlanma gibi sebeplerin rol aldığı düşünülse de kesin nedeni tam olarak çözülmüş değildir.…”

“…Şid-detli etkilenmiş kas dokusunda fiber yapılarının yerini konnektif ve yağ dokusu almaktadır. Rejenere [1][2][3][4]6 İmmünohis-tokimyasal olarak P62 boyamasında, görüntülenen liflerin yaklaşık %20'sinde vakuollü liflerin vakuolsüz sitoplazmalarında kıvrımlı, doğrusal ya da küçük yuvarlak agregatlar şeklinde pozitif reaksiyon izlenmektedir. İntrasitoplazmik inklüzyonlar şeklinde TDP-43 immünoreaktivitesi rapor edilmiştir.…”