Genetic landscape of congenital pouch colon: systematic review and functional enrichment study

Despite extensive clinical documentation, few studies have explored the genetic basis of congenital pouch colon (CPC) which is crucial for early detection, personalized treatment, and genetic counselling.

To compile the information on the genetic basis of CPC and the functional enrichment of underlying molecular pathways.

The review was conducted in accordance with PRISMA guidelines. The implicated genes were investigated for underlying molecular pathways. A network was subsequently created on String-database followed by gene-ontology analysis.

The study included 20 CPC cases and 52 controls (across 4 studies). Numerous variants, including 24 missense SNPs, 63 frameshift variants, and stop-gain/stop-loss mutations in 11 genes were identified. Notable genetic markers included MUC5B, FRG1, and TAF1B, with potential roles in mucosal barrier functions, colonic muscular development, and ribosomal RNA transcription, respectively. Copy number variants and lnc-EPB41-1-1 were also implicated. Genetic hotspots were identified on chromosomes 11, 17 and 16. RGPD2 and RGPD4, contributing to GTPase activator activity and known to be associated with bowel/colon, were differentially expressed. Pathway analysis highlighted Wnt and HOX pathways, with JAG1 and MLL relevant to CPC pathogenesis.

The study integrates genetic evidence and pathway analysis, shedding light on the complex genetic architecture of CPC. While the importance of genetic markers in the etiopathogenesis of CPC is underscored, the need for validating the findings on larger cohorts, diverse populations and through functional studies is suggested.