{"doi":"10.1172/jci.insight.168955","title":"Transcriptional profiling of rare acantholytic disorders suggests common mechanisms of pathogenesis","abstract":"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.","journal":"JCI Insight","year":2023,"id":335497,"datarank":0.9068676327914105,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"self_citation_contribution":0.47032413238937254,"citation_network_contribution":0.43654350040203793,"self_endowment_contribution":0.47032413238937254,"citer_contribution":0.43654350040203793,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":15,"citers_with_citation_signal":10,"citers_with_endowment":10,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9596,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":376492,"name":"Hope E. Burks","orcid":"0000-0002-2433-8423","position":1,"is_corresponding":false},{"id":494033,"name":"Ziyou Ren","orcid":"0000-0001-7127-4197","position":2,"is_corresponding":false},{"id":563463,"name":"Jennifer L. Koetsier","orcid":"0000-0001-7588-4726","position":3,"is_corresponding":false},{"id":12819,"name":"Lam C. Tsoi","orcid":"0000-0003-1627-5722","position":4,"is_corresponding":false},{"id":233181,"name":"Paul W. Harms","orcid":"0000-0002-0802-2883","position":5,"is_corresponding":false},{"id":12809,"name":"Xianying Xing","orcid":"0000-0003-4227-6868","position":6,"is_corresponding":false},{"id":249274,"name":"Joseph Kirma","orcid":"0000-0002-2890-6897","position":7,"is_corresponding":false},{"id":812232,"name":"Robert M. Harmon","orcid":"0000-0003-4843-0168","position":8,"is_corresponding":false},{"id":563462,"name":"Lisa M. Godsel","orcid":"0000-0001-5637-1773","position":9,"is_corresponding":false},{"id":250431,"name":"Abbey Perl","orcid":"0000-0002-4093-1833","position":10,"is_corresponding":false},{"id":12829,"name":"Jóhann E. Guðjónsson","orcid":"0000-0002-0080-0812","position":11,"is_corresponding":false},{"id":305159,"name":"Kathleen J. Green","orcid":"0000-0001-7332-5867","position":12,"is_corresponding":false},{"id":344824,"name":"Quinn R. Roth‐Carter","orcid":"0000-0002-3194-8668","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:09:58.338267Z","pmid":"37471166","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}