{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:45:44Z","timestamp":1792899944874,"version":"4.5.0"},"reference-count":13,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Dermatol"],"published-print":{"date-parts":[[2023,7,1]]},"abstract":"<jats:sec id=\"ab-dbr230005-4\"><jats:title>Importance<\/jats:title><jats:p>Grover disease (GD), a truncal eruption that typically occurs in older individuals, is exacerbated by sweating, irradiation, cancers, medications, kidney failure, and organ transplantation. The pathobiology of GD remains unknown.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr230005-5\"><jats:title>Objective<\/jats:title><jats:p>To determine if damaging somatic single-nucleotide variants (SNVs) are associated with GD.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr230005-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>In this retrospective case series, we identified consecutive patients from a dermatopathology archive over a 4-year period (January 2007 to December 2011) who had 1 biopsy with a clinical diagnosis of GD confirmed via histopathologic findings and another non-GD biopsy. Participant DNA was extracted from both biopsy tissues and sequenced to high depth with a 51-gene panel to screen for SNVs in genes previously associated with acantholysis and Mendelian disorders of cornification. Analysis took place between 2021 and 2023.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr230005-7\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Comparative analysis of sequencing data from paired GD and control tissue was employed to identify SNVs predicted to affect gene function, which were exclusive to, or highly enriched in, GD tissue.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr230005-8\"><jats:title>Results<\/jats:title><jats:p>Overall, 12 of 15 cases of GD (12 men and 3 women; mean [SD] age, 68.3 [10.0] years) were associated with C&amp;amp;gt;T or G&amp;amp;gt;A <jats:italic>ATP2A2<\/jats:italic> SNVs in GD tissue; all were predicted to be highly damaging via combined annotation dependent depletion (CADD) scores, and 4 were previously associated with Darier disease. In 9 cases (75%), the GD-associated <jats:italic>ATP2A2<\/jats:italic> SNV was absent from control tissue DNA, and in 3 cases (25%), <jats:italic>ATP2A2<\/jats:italic> SNVs were enriched 4- to 22-fold in GD vs control tissue.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr230005-9\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>In this case series study of 15 patients, damaging somatic <jats:italic>ATP2A2<\/jats:italic> SNVs were associated with GD. This discovery expands the spectrum of acantholytic disorders associated with <jats:italic>ATP2A2<\/jats:italic> SNVs and highlights the role of somatic variation in acquired disorders.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamadermatol.2023.1139","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T15:01:44Z","timestamp":1684335704000},"page":"745","source":"Crossref","is-referenced-by-count":26,"title":["Association of Somatic <i>ATP2A2<\/i> Damaging Variants With Grover Disease"],"prefix":"10.1001","volume":"159","author":[{"given":"Devin","family":"Seli","sequence":"first","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine T.","family":"Ellis","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut"},{"name":"Department of Genetics, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Goldust","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadim","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut"},{"name":"Department of Genetics, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronghua","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"McNiff","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut"},{"name":"Department of Pathology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A.","family":"Choate","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut"},{"name":"Department of Genetics, Yale University School of Medicine, New Haven, Connecticut"},{"name":"Department of Pathology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"2","key":"dbr230005r1","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1111\/ajd.2004.45.issue-2","article-title":"Grover\u2019s disease: 34 years on.","volume":"45","author":"Quirk","year":"2004","journal-title":"Australas J Dermatol"},{"issue":"3","key":"dbr230005r2","doi-asserted-by":"publisher","first-page":"229","DOI":"10.4065\/74.3.229","article-title":"Grover\u2019s disease: clinicopathologic review of 72 cases.","volume":"74","author":"Davis","year":"1999","journal-title":"Mayo Clin Proc"},{"issue":"3","key":"dbr230005r3","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1046\/j.1523-1747.2003.12410.x","article-title":"Mutations in the sarcoplasmic\/endoplasmic reticulum Ca2+ ATPase isoform cause Darier\u2019s disease.","volume":"121","author":"Dhitavat","year":"2003","journal-title":"J Invest Dermatol"},{"issue":"9","key":"dbr230005r4","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1111\/ijd.2012.51.issue-9","article-title":"The ATP2A2 gene in patients with Darier\u2019s disease: one novel splicing mutation.","volume":"51","author":"Shi","year":"2012","journal-title":"Int J Dermatol"},{"issue":"48","key":"dbr230005r5","doi-asserted-by":"publisher","first-page":"47877","DOI":"10.1074\/jbc.M306784200","article-title":"Dissection of the functional differences between sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) 1 and 2 isoforms and characterization of Darier disease (SERCA2) mutants by steady-state and transient kinetic analyses.","volume":"278","author":"Dode","year":"2003","journal-title":"J Biol Chem"},{"issue":"10","key":"dbr230005r6","doi-asserted-by":"publisher","first-page":"e633","DOI":"10.1111\/jdv.v34.10","article-title":"A case of type 1 segmental Darier disease showing widespread Blaschkoid skin lesions with p.P160L mutation in 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High burden and pervasive positive selection of somatic mutations in normal human skin.","volume":"348","author":"Martincorena","year":"2015","journal-title":"Science"},{"issue":"8","key":"dbr230005r10","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1038\/modpathol.3800837","article-title":"FGFR3 mutations in seborrheic keratoses are already present in flat lesions and associated with age and localization.","volume":"20","author":"Hafner","year":"2007","journal-title":"Mod Pathol"},{"issue":"3","key":"dbr230005r11","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1096\/fsb2.v25.3","article-title":"The calcium ATPase SERCA2 regulates desmoplakin dynamics and intercellular adhesive strength through modulation of PKC&a; signaling.","volume":"25","author":"Hobbs","year":"2011","journal-title":"FASEB J"},{"issue":"3","key":"dbr230005r12","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1111\/j.1365-2133.2000.03736.x","article-title":"Grover\u2019s disease, despite histological similarity to Darier\u2019s disease, does not share an abnormality in the ATP2A2 gene.","volume":"143","author":"Powell","year":"2000","journal-title":"Br J Dermatol"},{"issue":"2","key":"dbr230005r13","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1159\/000343172","article-title":"Grover\u2019s disease following multiple bilateral Blaschko lines: a rare clinical presentation with genetic and electron microscopic analyses.","volume":"225","author":"Asahina","year":"2012","journal-title":"Dermatology"}],"container-title":["JAMA Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamadermatology\/articlepdf\/2805259\/jamadermatology_seli_2023_br_230005_1689096819.98059.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T15:22:35Z","timestamp":1689780155000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamadermatology\/fullarticle\/2805259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,1]]},"references-count":13,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamadermatol.2023.1139","relation":{},"ISSN":["2168-6068"],"issn-type":[{"value":"2168-6068","type":"print"}],"subject":[],"published":{"date-parts":[[2023,7,1]]}}}