Uncovering Genetic and Signaling Pathway Alterations in Pompe Disease through Bioinformatics Approaches

Pompe disease is an autosomal recessive genetic disorder characterized by the accumulation of glycogen, a complex sugar, in the body cells. This pathological accumulation results from a deficiency of the enzyme acid alpha-glucosidase (GAA), which normally catalyzes glycogen breakdown. Excess glycogen predominantly accumulates in organs and tissues, especially in muscles, leading to their progressive degradation. In this study, we analyzed the microarray data corresponding to GSETA. The samples were classified into five groups, and differential gene expression analysis was performed in the R environment. Genes with logFC > and p-value < were selected. Subsequently, a protein-protein interaction (PPI) network was constructed, and five distinct CytoHubba algorithms were applied to identify the hub genes in each group. The overlapping hub genes across these methods were selected as the core set of genes. Functional enrichment and pathway analyses were performed using the DAVID platform. The R-based analysis identified ۱۵۰, ۱Yε, ^^, and ۹ genes in groups, Y, AA genes in group , and ۹ genes in group ۲. After hub gene screening, ۱ genes (group ۱), three genes (group Y), one gene (group), and ۱۵ genes (group ε) were identified. The principal pathways were mainly related to muscle function and immune system mechanisms, which were examined in detail in this study. This study highlights the genes potentially involved in the progression of Pompe disease, thereby contributing to a deeper understanding of its molecular mechanisms. These insights may facilitate the development of therapeutic strategies, including drug design and gene therapy. Furthermore, the evaluation of gene expression in the context of enzyme replacement therapy may provide additional clarity on the mechanisms of action of drugs.

Keywords:

Pompe disease , bioinformatics , genetic disorder , signaling pathways