Institute of Precision Medicine, Furtwangen University, Furtwangen, Germany.
Friedrich-Baur-Institute at the Department of Neurology, LMU University Hospital, Ludwig Maximilian University, Munich, Germany.
Commun Biol. 2024 May 25;7(1):640. doi: 10.1038/s42003-024-06325-z.
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common autosomal dominant muscle disorders, yet no cure or amelioration exists. The clinical presentation is diverse, making it difficult to identify the actual driving pathomechanism among many downstream events. To unravel this complexity, we performed a meta-analysis of 13 original omics datasets (in total 171 FSHD and 129 control samples). Our approach confirmed previous findings about the disease pathology and specified them further. We confirmed increased expression of former proposed DUX4 biomarkers, and furthermore impairment of the respiratory chain. Notably, the meta-analysis provides insights about so far not reported pathways, including misregulation of neuromuscular junction protein encoding genes, downregulation of the spliceosome, and extensive alterations of nuclear envelope protein expression. Finally, we developed a publicly available shiny app to provide a platform for researchers who want to search our analysis for genes of interest in the future.
面肩肱型肌营养不良症（FSHD）是最常见的常染色体显性肌肉疾病之一，但目前尚无治愈或改善方法。其临床表现多种多样，使得许多下游事件之间的实际致病机制难以确定。为了解开这种复杂性，我们对 13 个原始组学数据集（总共 171 个 FSHD 和 129 个对照样本）进行了荟萃分析。我们的方法证实了以前关于疾病病理的发现，并进一步对其进行了说明。我们证实了以前提出的 DUX4 生物标志物的表达增加，以及呼吸链的损伤。值得注意的是，荟萃分析提供了关于迄今为止未报道的途径的见解，包括神经肌肉接头蛋白编码基因的失调、剪接体的下调以及核膜蛋白表达的广泛改变。最后，我们开发了一个可公开获取的 shiny 应用程序，为未来希望在我们的分析中搜索感兴趣基因的研究人员提供了一个平台。
