Increase in cathepsin K gene expression in Duchenne muscular dystrophy skeletal muscle

• Published in: Neuropathology 2024-12, Vol.44 (6), p.411-421
• Main Authors: Kimura, Shigemi, Miyake, Noriko, Ozasa, Shiro, Ueno, Hiroe, Ohtani, Yoshinobu, Takaoka, Yutaka, Nishino, Ichizo
• Format: Article
• Language: English
• Subjects: Asymptomatic; Cathepsin K; Cathepsin K - biosynthesis; Cathepsin K - genetics; Cathepsin K - metabolism; Child; Crystallin; Duchenne muscular dystrophy; Duchenne's muscular dystrophy; Dystrophin; Fibrosis; Gene Expression; Humans; K gene; Male; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscular dystrophy; Muscular Dystrophy, Duchenne - genetics; Muscular Dystrophy, Duchenne - metabolism; Muscular Dystrophy, Duchenne - pathology; Musculoskeletal system; Myosin; Necrosis; Patients; Phenotypes; RNA sequence; Skeletal muscle; therapy
• ISSN: 0919-6544; 1440-1789; 1440-1789
• DOI: 10.1111/neup.12995

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 16‐fold change (P