To detect potential pathways and target genes in infantile Pompe patients using computational analysis

Area of Science:

• Genetics and Genomics
• Molecular Biology
• Biochemistry

Background:

• Pompe disease (PD), a genetic disorder caused by GAA gene mutations, leads to progressive muscle weakness.
• Enzyme replacement therapy (ERT) is the primary treatment, but patient responses are variable.
• Understanding the molecular mechanisms behind ERT response variability is crucial for improving patient outcomes.

Purpose of the Study:

• To identify key genes and molecular pathways involved in the response to ERT in Pompe disease.
• To investigate potential mechanisms underlying differential responses to ERT.
• To discover biomarkers for predicting ERT efficacy and patient prognosis.

Main Methods:

• Analysis of Gene Expression Omnibus (GEO) dataset GSE38680, including muscle samples from PD patients.
• Differential gene expression (DEG) analysis using BRB-Array Tools.
• Functional enrichment analysis of DEGs using DAVID, Gene Ontology (GO), KEGG, and STRING databases.

Main Results:

• A significant number of differentially expressed genes (DEGs) were identified in both biceps (1727) and quadriceps (1198) muscle groups.
• DEGs were notably enriched in patients with a poor response to ERT at 52 weeks.
• The WNT signaling pathway, along with vascular smooth muscle contraction, lysosomes, autophagy, actin cytoskeleton regulation, and inflammatory response, were significantly associated with DEGs and poor ERT response.

Conclusions:

• Specific genes within the WNT signaling pathway (e.g., WNT11, WNT5A, CTNNB1) and other pathways are implicated in poor ERT response in Pompe disease.
• These identified genes and pathways can serve as potential biomarkers for predicting ERT efficacy.
• Findings support the development of targeted therapies and improved diagnostic strategies for Pompe disease, potentially integrated into neonatal screening.