Differential Transcriptome Analysis of Intrauterine UPD6pat Fetuses With Distinct Phenotypes.

OBJECTIVE

Uniparental disomy of chromosome 6, typically paternal in origin (UPD6pat), results in significant phenotypic variability across different cases. This study integrates transcriptome-wide profiling of amniotic fluid cell-free RNA (cfRNA) with molecular diagnostics to elucidate the gene expression landscape and pathway dysregulation in two phenotypically distinct UPD6pat cases.

METHODS

RNA sequencing (RNA-seq) was performed on amniotic fluid supernatants from two UPD6pat fetuses and two gestational age-matched controls.

RESULTS

Differential expression analysis revealed 372 significantly dysregulated genes (242 upregulated and 130 downregulated; p < 0.05, |logFC| ≥ 0.5) enriched in pathways related to glucose metabolism, neurodegenerative diseases, and cellular processes. Gene set enrichment analysis (GSEA) further highlighted UPD6pat-associated perturbations in type 1 diabetes and glycosylphosphatidylinositol biosynthesis pathways. Phenotype-specific analysis revealed opposing expression trends in growth restriction genes and clubfoot-related genes (EP300 and CHD7), with protein-protein interaction (PPI) networks implicating epigenetic modulation and cytoskeletal dynamics as potential drivers of phenotypic divergence.

CONCLUSION

Despite limitations in sample size, our findings underscore the utility of amniotic fluid cfRNA analysis as a noninvasive tool for prenatal diagnostics and highlight novel targets for further functional validation.