Comprehensive Catalog of Variants Potentially Associated with Hidradenitis Suppurativa, Including Newly Identified Variants from a Cohort of 100 Patients

Abstract

Hidradenitis suppurativa (HS) is a chronic skin disease characterized by painful, recurrent abscesses, nodules, and scarring, primarily in skin folds. The exact causes of HS are multifactorial, involving genetic, hormonal, and environmental factors. It is associated with systemic diseases such as metabolic syndrome and inflammatory bowel disease. Genetic studies have identified mutations in the γ-secretase complex that affect Notch signaling pathways critical for skin cell regulation. Despite its high heritability, most reported HS cases do not follow a simple genetic pattern. In this article, we performed whole-exome sequencing (WES) on a cohort of 100 individuals with HS, and we provide a comprehensive review of the variants known to be described or associated with HS. 91 variants were associated with the γ-secretase complex, and 78 variants were associated with other genes involved in the Notch pathway, keratinization, or immune response. Through this new genetic analysis, we have added ten new variants to the existing catalogs. All variants are available in a .vcf file and are provided as a resource for future studies.

Keywords: hidradenitis suppurativa; inflammation; nicastrin; notch pathway; whole-exome sequencing; γ-secretase.

Figure 1

Computational models of the NCSTN protein. In cyan, red, and grey: the cytosolic, transmembrane (TM), and extracellular regions or domains. In pink: the signal peptide responsible for addressing the protein to the membrane. In green: the small lobe that would interact with the substrate. In dark blue: the large lobe. (a) Reference (WT), (b) p.Ala300TrpfsTer20, (c) p.Arg429*, and (d) p.Trp648* variant models.