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.
摘要：
肌营养不良蛋白病是由肌营养不良蛋白基因的改变引起的。严重的表型，杜氏肌营养不良症（DMD），是由于骨骼肌中缺乏肌营养不良蛋白引起的，导致坏死和再生纤维，炎症细胞，和肌肉纤维化。进行性肌肉无力是这种情况的特征发现。这里,我们遇到了一例罕见的10岁无症状肌萎缩蛋白病患者,无肌萎缩蛋白表达,我们调查了没有肌无力的原因,以获得DMD的治疗见解.使用RNA-seq分析，在骨骼肌中的基因表达在无症状的肌营养不良症患者之间进行了比较，三个典型的DMD患者,和两名没有肌营养不良症的患者，他们过着正常的日常生活。组织蛋白酶K(CTSK),肌球蛋白重链3（MYH3），结节调节剂3样基因表现出>8倍的变化，而结晶蛋白mu基因（CRYM）在典型DMD患者中的表达与在无症状肌萎缩蛋白病患者中的表达相比，变化<1/8倍。此外,CTSK和MYH3表达变化>16倍(P<0.01),而CRYM在典型DMD患者中的表达变化<1/16倍(P<0.01),与在无肌萎缩蛋白病者中的表达相比。CTSK在骨骼肌损失中起着至关重要的作用，纤维化，和肌肉注射心脏毒素后的炎症，最常见的诱发肌肉损伤的试剂之一。CTSK表达增加与DMD患者的肌肉损伤或坏死有关。无症状性肌营养不良病患者缺乏肌肉无力可能归因于肌肉中CTSK的低表达。据我们所知,这是首次报告证明CTSK在具有典型表型的DMD患者骨骼肌中的表达明显高于无肌营养不良蛋白病的患者.
