Transcriptional profiling of rare acantholytic disorders suggests common mechanisms of pathogenesis

Quinn R. Roth-Carter, Hope E. Burks, Ziyou Ren, Jennifer L. Koetsier, Lam C. Tsoi, Paul W. Harms, Xianying Xing, Joseph Kirma, Robert M. Harmon, Lisa M. Godsel, Abbey L. Perl, Johann E. Gudjonsson, Kathleen J. Green

Research output: Contribution to journalArticlepeer-review


Darier, Hailey-Hailey, and Grover diseases are rare acantholytic skin diseases. While these diseases have different underlying causes, they share defects in cell-cell adhesion in the epidermis and desmosome organization. To better understand the underlying mechanisms leading to disease in these conditions, we performed RNA-seq on lesional skin samples from patients. The transcriptomic profiles of Darier, Hailey-Hailey, and Grover diseases were found to share a remarkable overlap, which did not extend to other common inflammatory skin diseases. Analysis of enriched pathways showed a shared increase in keratinocyte differentiation, and a decrease in cell adhesion and actin organization pathways in Darier, Hailey-Hailey, and Grover diseases. Direct comparison to atopic dermatitis and psoriasis showed that the downregulation in actin organization pathways was a unique feature in the acantholytic skin diseases. Furthermore, upstream regulator analysis suggested that a decrease in SRF/MRTF activity was responsible for the downregulation of actin organization pathways. Staining for MRTFA in lesional skin samples showed a decrease in nuclear MRTFA in patient skin compared with normal skin. These findings highlight the significant level of similarity in the transcriptome of Darier, Hailey-Hailey, and Grover diseases, and identify decreases in actin organization pathways as a unique signature present in these conditions.

Original languageEnglish (US)
Article numbere168955
JournalJCI Insight
Issue number16
StatePublished - 2023

ASJC Scopus subject areas

  • Medicine(all)


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