{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:38:48Z","timestamp":1779237528327,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,12,20]],"date-time":"2020-12-20T00:00:00Z","timestamp":1608422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hailey\u2013Hailey disease (HHD; OMIM: 169600) is an autosomal dominate genodermatosis, characterized by recurrent blisters and erosions clinically and remarkable acantholysis pathologically. The underlying pathogenic factor is the mutation of <jats:italic>ATP2C1<\/jats:italic> gene (OMIM: 604384), which encodes secretory pathway Ca<jats:sup>2+<\/jats:sup>\/Mn<jats:sup>2+<\/jats:sup>\u2010ATPase (SPCA1). Skin folds are the predilection site of HHD. Atypical cases with a generalized pattern have rarely been reported, making it prone to misdiagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we presented three Chinese pedigrees of Hailey\u2013Hailey disease with generalized skin lesions. <jats:italic>ATP2C1<\/jats:italic> mutations were screened by DNA sequencing and their transcripts were further confirmed by minigene assay. We also performed a literature review of previously published generalized HHD over past two decades together with our cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three splice\u2010site mutations were identified: c.2487+1G&gt;A, c.2126+1G&gt;A, and c.1891\u20102A&gt;G, which resulted in an exon 25\u2010truncated transcript, two exon 22\u2010truncated transcripts, and two exon 21\u2010truncated transcripts, respectively. The c.2487+1G&gt;A and the c.1891\u20102A&gt;G mutations are novel mutations which have not been reported before. No clustered mutations of <jats:italic>ATP2C1<\/jats:italic> gene were found in generalized HHD patients in literature along with our novel mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We found no hot spot mutations in <jats:italic>ATP2C1<\/jats:italic> correlated with the generalized pattern of HHD. Our study expanded the spectrum of <jats:italic>ATP2C1<\/jats:italic> mutations, which would be useful for disease diagnosis and genetic counseling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1580","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T09:57:17Z","timestamp":1608544637000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Generalized Hailey\u2013Hailey disease: Novel splice\u2010site mutations of <i>ATP2C1<\/i> gene in Chinese population and a literature review"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6433-9298","authenticated-orcid":false,"given":"Lu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Dermatology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 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