O26: Resolution of large complex VNTRs with HiFi sequencing: Applications in LPA Kringle IV-type 2 repeat and D4Z4 repeat

profiled with 850k-probe methylation Illumina arrays.Integration of transcriptomic and epigenomic data was performed to identify genes with concordant expression and methylation changes.RNA quality metrics (RIN and DV200) showed no significant differences between FXTAS and control samples.Results: RNA quality metrics (RIN and DV200) showed no significant differences between FXTAS and control samples.Gene expression analysis revealed 263 differentially expressed genes (DEGs) in FXTAS, with 98 upregulated and 165 downregulated, including 72 known FMR1 targets.FMR1expression was lower in FXTAS patients compared to controls.Pathway enrichment analysis indicated dysregulation in RNA metabolism, oxidative stress response, and mitochondrial function, implicating genes such as RBFOX1, SOD1, and NDUFA6.Methylation analysis identified497 differentially methylated probes, with 224 upregulated and 273 downregulated genes in FXTAS.Integration of transcriptomic and epigenomic data revealed discrete inverse correlations between expression and methylation.Functional analysis highlighted enrichment in pathways related to extracellular matrix structure, protein degradation, and immune modulation.integration analysis of isoforms, local alternative splicing and proteome are ongoing. Conclusion:This study provides insights into the molecular mechanisms of FXTAS, identifying key dysregulated genes and pathways involved in RNA splicing, neuronal development, oxidative stress response, and immune modulation.The integration of gene expression and methylation data underscores the importance of epigenetic regulation in FXTAS pathogenesis, offering potential targets for therapeutic intervention.These findings advance our understanding of the complex regulatory mechanisms underlying FXTAS and may inform future research and treatment strategies.