Ligong Lin*,Youming Pang*,#, Fei Zhang**, Bo Feng*, Guangming Dai*


*Department of hand,foot and ankle surgery, The third affiliated hospital of Inner Mongolia Medical University(Inner Mongolia Baogang hospital), Baotou, 014010, China - **Department of Orthopaedics, The third affiliated hospital of Inner Mongolia Medical University (Inner Mongolia Baogang hospital), Baotou 014010, China


Objective: We sought to find genes that cause congenital clubfoot and to identify the effects of the Pitx1 gene in the pathogenesis of congenital clubfoot.

Methods: Download data on congenital clubfoot in the GEO database. For the gene expression profile of mice, we performed differential expression analysis. We performed co-expression analysis of differentially expressed genes in congenital clubfoot, and simultaneously explored disease-related dysfunction modules and identified the driver genes for each module, and performed GO function and KEGG pathway enrichment analysis, respectively. Non-coding RNAs (ncRNAs) and transcription factors that have significant regulatory effects on the module are predicted based on hypergeometric tests, and the core ncRNA and core TF are found in combination with connectivity analysis.

Results: A total of 1101 differentially expressed genes were found in the mouse gene. Three co-expression modules were obtained by weighted gene co-expression network analysis, in which Mynn, Snca, and Actn2 genes have existing regulation in dysfunction modules. Enrichment analysis of GO function and KEGG pathway revealed that the module genes are significantly involved in biological processes, including skeletal muscle contraction, blood circulation, and regulation of the circulatory system, as well as regulation of involved signaling pathways including lysosomes, myocardial contraction, oxidative phosphorylation, and nerves. Nutritional factors. By pivotal analysis and binding connectivity calculations, we identified the core ncRNA (let-7d-5p, Terc) and the core transcription factor (Myod1, Myog) that regulate the genes of the congenital clubfoot.

Conclusion: Our work reveals a core dysfunction module and potential regulatory factors regulated by the Pitx gene in congenital clubfoot, which enhances our understanding of its pathogenesis.


Congenital clubfoot, Pitx1, difference analysis, enrichment analysis, regulatory factor.