Integrative Bioinformatics Analyses Reveal X Chromosome Inactivation Escape Genes Dosage Dysregulation Is the Primary...

Turner syndrome is a rare disorder resulting from abnormalities in the number or structure of a single X chromosome. It stands as the sole survivable monosomy observed in humans. Individuals affected by Turner syndrome commonly face significant complications, including impaired gonadal development, short stature, and intellectual disabilities. Despite extensive research, the complete understanding of the pathogenesis behind Turner syndrome remains elusive.

This study aimed to elucidate the molecular mechanisms of Turner syndrome by identifying key X chromosome inactivation escape genes and exploring their potential contributions to genotype-phenotype correlations and therapeutic targets through integrative bioinformatics analyses.

The study included three RNA-seq datasets, consisting of 72 patients with Turner syndrome and 58 individuals with normal cytogenetics. Differentially expressed gene analysis, protein-protein interaction network analysis, and functional enrichment analysis were conducted to ascertain hub genes. Furthermore, pivotal lncRNAs and transcription factors were identified through competitive endogenous RNA network analysis and transcription factor enrichment analyses.

This study made a significant contribution by exploring the relationship between Turner syndrome genotypes and various phenotypes at the transcriptomic level. We found hub genes associated with hormone regulation, including growth hormone. Moreover, we highlighted 10 crucial X chromosome inactivation escape genes (ASMTL, CD99, DHRSX, EIF1AX, JPX, KDM5C, KDM6A, SLC25A6, XIST, and ZFX), which may serve as core pathogenic factors in Turner Syndrome. Additionally, based on our findings, we proposed certain drugs as potential new therapeutic strategies for Turner Syndrome.

Our study provides substantial evidence supporting the correlation between genotype and various phenotypes in Turner Syndrome. Furthermore, we shed light on the potential pathogenic significance of X chromosome inactivation escape genes. These findings open up new possibilities for therapeutic interventions.