Affiliation:
1. Department of Pediatrics Kumamoto Takumadai Rehabilitation Hospital Kumamoto Japan
2. Data Science Center for Medicine and Hospital Management Toyama University Hospital Toyama Japan
3. Department of Medical Systems Kobe University Graduate School of Medicine Kobe Japan
4. Department of Human Genetics Research Institute, National Center for Global Health and Medicine Tokyo Japan
5. Department of Pediatrics Kumamoto University Hospital Kumamoto Japan
6. Faculty of Health Sciences Kobe Tokiwa University Kobe Japan
7. Department of Neuromuscular Research National Institute of Neuroscience, National Center of Neurology and Psychiatry Tokyo Japan
Abstract
Dystrophinopathy is caused by alterations in the dystrophin gene. The severe phenotype, Duchenne muscular dystrophy (DMD), is caused by a lack of dystrophin in skeletal muscles, resulting in necrosis and regenerating fibers, inflammatory cells, and muscle fibrosis. Progressive muscle weakness is a characteristic finding of this condition. Here, we encountered a rare case of a 10‐year‐old patient with asymptomatic dystrophinopathy with no dystrophin expression and investigated the reason for the absence of muscle weakness to obtain therapeutic insights for DMD. Using RNA‐seq analysis, gene expression in skeletal muscles was compared among patients with asymptomatic dystrophinopathy, three patients with typical DMD, and two patients without dystrophinopathy who were leading normal daily lives. Cathepsin K (CTSK), myosin heavy chain 3 (MYH3), and nodal modulator 3‐like genes exhibited a >8‐fold change, whereas crystallin mu gene (CRYM) showed a <1/8‐fold change in patients with typical DMD compared with their expression in the patient with asymptomatic dystrophinopathy. Additionally, CTSK and MYH3 expression exhibited a >16‐fold change (P < 0.01), whereas CRYM expression showed a <1/16‐fold change (P < 0.01) in patients with typical DMD compared with their expression in those without dystrophinopathy. CTSK plays an essential role in skeletal muscle loss, fibrosis, and inflammation in response to muscles injected with cardiotoxin, one of the most common reagents that induce muscle injury. Increased CTSK expression is associated with muscle injury or necrosis in patients with DMD. The lack of muscle weakness in the patient with asymptomatic dystrophinopathy might be attributed to the low CTSK expression in the muscles. To the best of our knowledge, this is the first report to demonstrate that CTSK expression was significantly higher in the skeletal muscles of patients with DMD with a typical phenotype than in those without dystrophinopathy.