Genetic mutations in pyoderma gangrenosum, hidradenitis suppurativa, and associated autoinflammatory syndromes: Insights into pathogenic mechanisms and shared pathways

Abstract

The review article by Takashi K. Satoh1 discusses dermatological conditions such as pyoderma gangrenosum (PG), hidradenitis suppurativa (HS), and related autoinflammatory syndromes including pyogenic arthritis, PG, and acne (PAPA), PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome, PG, acne, and HS (PASH) and pyogenic arthritis, PG, acne, and HS (PAPASH), which are characterized by chronic inflammation and tissue damage. The author highlights recent genetic research identifying specific mutations linked to these disorders, aiming to summarize the current understanding of their genetic background and pathophysiology. Here, we aim to highlight the importance of bioinformatics in analyzing whole-exome sequencing (WES) data for syndromic HS (sHS) patients, specifically in identifying disrupted biological signaling pathways. While endotype-phenotype correlation is crucial for diagnostic purposes, focusing solely on genetic variations linked to the phenotype offers a limited perspective. A comprehensive understanding of the etiopathogenesis of HS-related autoinflammatory syndromes can be achieved through a WES-based variant enrichment analysis (VEA), which offers a broader view beyond individual genetic variations, facilitating a deeper insight into the complex nature of sHS.