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

Hidradenitis suppurativa and Dowling-Degos disease are two independent rare diseases with characteristic clinical manifestations. The <i>PSENEN</i> gene encodes a critical subunit of the <i>γ</i>-secretase complex, mutations of which can independently or concurrently lead to hidradenitis suppurativa and Dowling-Degos disease. Given the rarity of pathogenic <i>PSENEN</i> 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 <i>PSENEN</i> 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 <i>PSENEN</i> mutations in relation to the clinical phenotypes of skin diseases. These findings contribute novel insights into genotype-phenotype correlations involving the <i>PSENEN</i> gene, expanding our understanding of these complex dermatologic disorders at the molecular level.