Pathogenic variants in <i>PSENEN</i> and <i>NCSTN</i> genes cause ‘follicular’ Dowling-Degos disease: Report of five unrelated Indian families

Background Follicular Dowling-Degos disease (DDD) is a rare clinically and histologically distinct genodermatosis. However, its genetic basis has not been well-studied. Objective To describe the clinical, histological, and mutational spectrum of follicular DDD in 10 patients from five unrelated Indian families. Methods Clinical and histological features of patients were recorded. Whole exome sequencing was done on the venous blood of probands and their family members, and its results were validated by Sanger sequencing. Results All patients presented with open comedones, small follicular keratotic papules, and fine pitted and shallow crateriform scars predominantly on the face, back and flexural sites. The skin biopsy showed follicular plugs along with downward elongation and branching of pigmented rete ridges confined to the follicular infundibulum. Whole exome sequencing revealed distinct pathogenic variants in the PSENEN (3 families) and NCSTN (2 families) genes of probands and their affected family members, as validated by Sanger sequencing. Limitations Functional significance of the gene mutations in disease pathogenesis could not be assessed by cell culture studies and knock-down experiments. Conclusion Our study identified PSENEN and NCSTN gene mutations as the genetic basis of follicular DDD. These genes encode proteins involved in the Notch signalling pathway and can potentially explain the predominantly folliculocentric phenotype of follicular DDD.