AUTHOR=Song Qiuhe , Zhang Chaowen , Xu Pengfei , Wang Jianqiao , Liao Fangfang , Xiao Qipeng , Mao Yousheng 

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

JOURNAL=Frontiers in Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1542909

DOI=10.3389/fmed.2025.1542909

ISSN=2296-858X

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.