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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.<\/jats:p>","DOI":"10.1172\/jci.insight.168955","type":"journal-article","created":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T12:00:34Z","timestamp":1689854434000},"source":"Crossref","is-referenced-by-count":27,"title":["Transcriptional profiling of rare acantholytic disorders suggests common mechanisms of pathogenesis"],"prefix":"10.1172","volume":"8","author":[{"given":"Quinn R.","family":"Roth-Carter","sequence":"first","affiliation":[{"name":"Department of Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2433-8423","authenticated-orcid":true,"given":"Hope E.","family":"Burks","sequence":"additional","affiliation":[{"name":"Department of Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyou","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Koetsier","sequence":"additional","affiliation":[{"name":"Department of Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1627-5722","authenticated-orcid":true,"given":"Lam C.","family":"Tsoi","sequence":"additional","affiliation":[{"name":"Department of Dermatology,"},{"name":"Department of Computational Medicine & Bioinformatics,"},{"name":"Department of Biostatistics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0802-2883","authenticated-orcid":true,"given":"Paul W.","family":"Harms","sequence":"additional","affiliation":[{"name":"Department of Dermatology,"},{"name":"Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4227-6868","authenticated-orcid":true,"given":"Xianying","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Dermatology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Kirma","sequence":"additional","affiliation":[{"name":"Department of Dermatology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4843-0168","authenticated-orcid":true,"given":"Robert M.","family":"Harmon","sequence":"additional","affiliation":[{"name":"Department of Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5637-1773","authenticated-orcid":true,"given":"Lisa M.","family":"Godsel","sequence":"additional","affiliation":[{"name":"Department of Pathology, and"},{"name":"Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbey L.","family":"Perl","sequence":"additional","affiliation":[{"name":"Department of Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0080-0812","authenticated-orcid":true,"given":"Johann E.","family":"Gudjonsson","sequence":"additional","affiliation":[{"name":"Department of Dermatology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7332-5867","authenticated-orcid":true,"given":"Kathleen J.","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Pathology, and"},{"name":"Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA."},{"name":"Robert H. 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