TDP-43 accumulation is common in myopathies with rimmed vacuoles

Excerpt

TAR-DNA-binding protein-43 (TDP-43) is a nuclear protein that is thought to play a regulatory role in gene expression. Ubiquitinated TDP-43 is found in cytoplasmic inclusions in motor neuron disease (MND), frontotemporal lobar degeneration (FTLD-TDP), and MND with FTLD [4]. This shared histopathological hallmark led to the classification of a new class of diseases, the TDP-43-proteinopathies [3]. Recently, TDP-43-positive inclusions have been described in skeletal muscle in sporadic inclusion body myositis (sIBM) and in IBM due to mutations in the valosin-containing protein (VCP) [6]. These myopathies are accompanied by vacuolar changes commonly known as rimmed vacuoles (although these vacuoles are morphologically not always rimmed). These characteristic morphological changes are not exclusive to sIBM and IBM with VCP-mutations but are also found in oculopharyngeal muscular dystrophy (OPMD) [2] and distal myopathies with rimmed vacuoles (DMRV), both of which are hereditary myopathies with inclusion bodies. Although DMRV are a genetically heterogeneous group of diseases, the term is often used in the context of the Nonaka myopathy with mutations of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene [5]. …