EMBO：复旦大学马竞/张天宇/宋楠等发现眼皮下垂元凶，并揭示其在骨骼肌发育中重要作用

Core Viewpoint - The study identifies FOXK2 gene mutations as a key cause of congenital myopathy associated with ptosis, expanding the understanding of FOXK2's role in skeletal muscle development and potential treatment strategies involving coenzyme Q10 [3][17]. Group 1: Genetic Findings - The research team discovered five novel mutations in the FOXK2 gene through whole-exome sequencing and Sanger sequencing in five affected families [5]. - Traditionally, ZFHX4 and COL25A1 were considered the main pathogenic genes, but many cases remained unexplained until this study [5]. Group 2: Mechanistic Insights - Animal models, including zebrafish and mice, were used to demonstrate the consequences of FOXK2 gene mutations, revealing disordered muscle fiber arrangement and decreased protein stability [8][14]. - FOXK2 regulates mitochondrial function through dual pathways: activating antioxidant genes and maintaining chromatin openness for mitochondrial-related gene regions [11]. Group 3: Treatment Implications - Coenzyme Q10 treatment for two weeks showed potential in reversing muscle abnormalities caused by FOXK2 mutations, improving mitochondrial function and alleviating skeletal muscle developmental defects [12][15]. - The study suggests that FOXK2 is crucial for skeletal muscle development and mitochondrial homeostasis, paving the way for future diagnostic and therapeutic strategies [17].