# PSENEN mutation in a Chinese family manifesting as concurrent hidradenitis suppurativa and Dowling-Degos disease: a case report of four generations

## TL;DR

A Chinese family with a PSENEN gene mutation shows both hidradenitis suppurativa and Dowling-Degos disease across four generations.

## Contribution

The study identifies a specific PSENEN gene deletion mutation linked to concurrent skin diseases in a multigenerational family.

## Key findings

- A deletion mutation (c.66delG) in the PSENEN gene was found in a Chinese family with both hidradenitis suppurativa and Dowling-Degos disease.
- The mutation was confirmed through whole-exome and Sanger sequencing, linking genotype to the observed skin phenotypes.
- The study expands understanding of PSENEN-related dermatologic disorders and their systemic comorbidities.

## Abstract

Hidradenitis suppurativa and Dowling-Degos disease are two independent rare diseases with characteristic clinical manifestations. The PSENEN gene encodes a critical subunit of the γ-secretase complex, mutations of which can independently or concurrently lead to hidradenitis suppurativa and Dowling-Degos disease. Given the rarity of pathogenic PSENEN mutations in the general population, further elucidation of their relationship with these conditions is warranted. We conducted an investigation on a multigenerational Chinese family encompassing 14 members, all of whom exhibited clinical manifestations of both hidradenitis suppurativa and Dowling-Degos disease. Diagnosis was established through pedigree analysis, clinical assessment, pathological examination, Twist whole-exome sequencing and Sanger sequencing. Genetic analysis revealed a deletion mutation (c.66delG) in the PSENEN gene located on chromosome 19, marking this mutation being associated with the clinical manifestations of both diseases. Additionally, this article reviews existing literature and discusses the potential systemic comorbidities associated with PSENEN mutations in relation to the clinical phenotypes of skin diseases. These findings contribute novel insights into genotype–phenotype correlations involving the PSENEN gene, expanding our understanding of these complex dermatologic disorders at the molecular level.