Di-Genic Inheritance in Genodermatoses: Insights from Two Consanguineous Cases in a Reference Lebanese Center within...

Genodermatoses refer to a group of heterogenous rare genetic diseases with cutaneous expression. Several genodermatoses present with multisystem involvement that can range from mild to life-threatening conditions leading to increased morbidity and mortality.

Given the paucity in the literature in the field of genodermatoses, especially in the Middle East and North Africa (MENA) region, and building upon the first established genodermatoses database based in Lebanon, this study aimed to decipher the genetic basis of two different types of skin-inherited diseases (androgenic alopecia and vitiligo).

We conducted a pilot study on two subjects with androgenic alopecia and vitiligo to investigate the possibility of a digenic inheritance model as a potential underlying mechanism for these conditions. Whole exome sequencing (WES) and Gene Expression Omnibus (GEO) DataSets were employed to validate the methodology and provide a foundation for future, larger-scale studies.

We identified two gene variants FOXC1(p.His484Tyr) and SMARCD1 (p.Arg351Cys) responsible for androgenic alopecia and HPS1(p.Ser566Ter) and ITK (p.Pro521Leu) responsible for vitiligo. Further analysis using GEO DataSets confirmed the association between the genes involved in each each disease.

This study identified novel candidate disease genes and inheritance model that could explain the underlying phenotypes that could open the door for a better-guided genomic approach for personalized treatment and early diagnosis.