Rimmed vacuoles in myofibers are thought to be due to the accumulation of autophagic vacuoles, and can be characteristic in certain myopathies with protein inclusions in myofibers. In this study, we performed a detailed clinical, molecular, and pathological characterization of Becker muscular dystrophy patients who have rimmed vacuoles in muscles. Among 65 Becker muscular dystrophy patients, we identified 12 patients who have rimmed vacuoles and 11 patients who have deletions in exons 45–48 in DMD gene. All patients having rimmed vacuoles showed milder clinical features compared to those without rimmed vacuoles. Interestingly, the rimmed vacuoles in Becker muscular dystrophy muscles seem to represent autophagic vacuoles and are also associated with polyubiquitinated protein aggregates. These findings support the notion that rimmed vacuoles can appear in Becker muscular dystrophy, and may be related to the chronic changes in muscle pathology induced by certain mutations in the DMD gene.
Malicdan MC, Noguchi S, Nonaka I, Saftig P, Nishino I (2008) Lysosomal myopathies: an excessive build-up in autophagosomes is too much to handle. Neuromuscul Disord 18: 521–529.
Raben N, Takikita S, Pittis MG, Bembi B, Marie SKN, et al. (2007) Deconstructing Pompe disease by analyzing single muscle fibers: to see the world in a grain of sand. Autophagy 3: 546–552.
Askanas V, Engel WK (2008) Inclusion-body myositis: muscle-fiber molecular pathology and possible pathogenic significance of its similarity to Alzheimer’s and Parkinson’s disease brains. Acta Neuropathol 116: 583–595.
Malicdan MC, Noguchi S, Nishino I (2007) Autophagy in a mouse model of distal myopathy with rimmed vacuoles of hereditary inclusion body myopathy. Autophagy 3: 396–398.
Malicdan MC, Noguchi S, Nonaka I, Hayashi YK, Nishino I (2007) A Gne knockout mouse expressing human GNE D176V mutation develops features similar to distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy. Hum Molec Genet 16: 2669–2682.
Takemitsu M, Nonaka I, Sugita H (1993) Dystrophin-related protein in skeletal muscles in neuromuscular disorders: immunohistochemical study. Acta Neuropathol 85: 256–259.
Deburgrave N, Daoud F, Llense S, Barbot JC, Récan D, et al. (2007) Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene. Hum Mutat 28: 183–195.
Koenig M, Beggs AH, Moyer M, Scherpf S, Heindrich K, et al. (1989) The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. Am J Hum Genet 45: 498–506.
Tasaki N, Yoshida K, Haruta S, Kouno H, Ichinose H, et al. (2001) X-linked dilated cardiomyopathy with a large hot-spot deletion in the dystrophin gene. Intern Med 40: 1215–1221.
Nakamura A, Yoshida K, Fukushima K, Ueda H, Urasawa N, et al. (2008) Follow-up of three patients with a large in-frame deletion of exons 45–55 in the Duchenne muscular dystrophy (DMD) gene. J Clin Neurosci 15: 757–763.
Yazaki M, Yoshida K, Nakamura A, Koyama J, Nanba T, et al. (1999) Clinical characteristics of aged Becker muscular dystrophy patients with onset after 30 years. Eur Neurol 42: 145–149.
Sugie K, Noguchi S, Kozuka Y, Arikawa-Hirasawa E, Tanaka M, et al. (2005) Autophagic vacuoles with sarcolemmal features delineate Danon disease and related myopathies. J Neuropathol Exp Neurol 64: 513–522.
Lawler JM (2011) Exacerbation of pathology by oxidative stress in respiratory and locomotor muscles with Duchenne muscular dystrophy. J Physiol 589: 2161–2170.
Broccolini A, Gidaro T, Cristofaro RD, Morosetti R, Gliubizzi C (2008) Hyposialylation of neprilysin possibly affects its expression and enzymatic activity in hereditary inclusion-body myopathy muscle. J Neurochem105: 971–981.
Broccolini A, Gidaro T, Morosetti R, Mirabella M (2009) Hereditary inclusion-body myopathy: clues on pathogenesis and possible therapy. Muscle Nerve 40: 340–349.
