{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:52:00Z","timestamp":1787320320709,"version":"build-2736575974"},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:00:00Z","timestamp":1695340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004756","name":"Emil Aaltosen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004756","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010746","name":"Suomen Ihotautil\u00e4\u00e4k\u00e4riyhdistys","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010746","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003125","name":"Suomen Kulttuurirahasto","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003125","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008723","name":"Suomen L\u00e4\u00e4ketieteen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008723","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2024,2]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Hereditary palmoplantar keratodermas (hPPKs) comprise a heterogeneous group of skin disorders characterized by persistent palmoplantar hyperkeratosis. Loss\u2010of\u2010function variants in a serine peptidase inhibitor,\n SERPINA12<\/jats:italic>\n , have recently been implicated in autosomal recessive diffuse hPPK. The disorder appears to share similarities with another hPPK associated with protease overactivity, namely Nagashima\u2010type PPK (NPPK) caused by biallelic variants in\n SERPINB7<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n \n The aim of this study was to enhance the understanding of the clinical and genetic characteristics of serine protease\u2010related hPPKs caused by variants in\n SERPINA12<\/jats:italic>\n and\n SERPINB7<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Whole\u2010exome sequencing (WES) was performed for hPPK patients. Haplotype analysis was completed for the patients with identified recessive\n SERPINA12<\/jats:italic>\n variants and their available family members. In addition, the current literature of\n SERPINA12<\/jats:italic>\n \u2010 and\n SERPINB7<\/jats:italic>\n \u2010related hPPKs was summarized.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The phenotype of\n SERPINA12<\/jats:italic>\n \u2010related hPPK was confirmed by reporting three new\n SERPINA12<\/jats:italic>\n patients, the first of European origin. A novel\n SERPINA12<\/jats:italic>\n c.1100G>A p.(Gly367Glu) missense variant was identified confirming that the variant spectrum of\n SERPINA12<\/jats:italic>\n include both truncating and missense variants. The previously reported\n SERPINA12<\/jats:italic>\n c.631C>T p.(Arg211*) was indicated enriched in the Finnish population due to a plausible founder effect. In addition,\n SERPINA12<\/jats:italic>\n hPPK patients were shown to share a similar phenotype to patients with recessive variants in\n SERPINB7<\/jats:italic>\n . The shared phenotype included diffuse transgradient PPK since birth or early childhood and frequent palmoplantar hyperhidrosis, aquagenic whitening and additional hyperkeratotic lesions in non\u2010palmoplantar areas.\n SERPINA12<\/jats:italic>\n and\n SERPINB7<\/jats:italic>\n hPPK patients cannot be distinguished without genetic analysis.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Recessive variants in\n SERPINA12<\/jats:italic>\n and\n SERPINB7<\/jats:italic>\n leading to protease overactivity and hPPK produce a similar phenotype, indistinguishable without genetic analysis.\n SERPINA12<\/jats:italic>\n variants should be assessed also in non\u2010Asian patients with diffuse transgradient PPK. Understanding the role of serine protease inhibitors will provide insights into the complex proteolytic network in epidermal homeostasis.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jdv.19498","type":"journal-article","created":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T20:28:35Z","timestamp":1694204915000},"page":"413-418","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A novel\n SERPINA12<\/i>\n variant and first European patients with diffuse palmoplantar keratoderma"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5182-9455","authenticated-orcid":false,"given":"E.","family":"Brandt","sequence":"first","affiliation":[{"name":"Department of Dermatology and Allergology, ERN\u2010Skin Center University of Helsinki and Helsinki University Central Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3623-2359","authenticated-orcid":false,"given":"L.","family":"Harjama","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, ERN\u2010Skin Center University of Helsinki and Helsinki University Central Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Elomaa","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center, Helsinki, Finland and Research Programs Unit, Stem Cells and Metabolism Research Program University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Saarela","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE) University of Helsinki Helsinki Finland"},{"name":"The Centre for Molecular Medicine Norway (NCMM) University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Donner","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE) University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Lappalainen","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, ERN\u2010Skin Center University of Helsinki and Helsinki University Central Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Kivirikko","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Department of Medical and Clinical Genetics University of Helsinki and Helsinki University Central Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ranki","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, ERN\u2010Skin Center University of Helsinki and Helsinki University Central Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Kere","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center, Helsinki, Finland and Research Programs Unit, Stem Cells and Metabolism Research Program University of Helsinki Helsinki Finland"},{"name":"Department of Biosciences and Nutrition Karolinska Institutet Huddinge Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Kettunen","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE) University of Helsinki Helsinki Finland"},{"name":"HUS Diagnostic Center, Division of Genetics and Clinical Pharmacology, Laboratory of Genetics University of Helsinki and Helsinki University Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Hannula\u2010Jouppi","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, ERN\u2010Skin Center University of Helsinki and Helsinki University Central Hospital Helsinki Finland"},{"name":"Folkh\u00e4lsan Research Center, Helsinki, Finland and Research Programs Unit, Stem Cells and Metabolism Research Program University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.14902"},{"key":"e_1_2_10_3_1","first-page":"704","article-title":"Loss\u2010of\u2010function variants in SERPINA12 underlie autosomal recessive palmoplantar keratoderma","volume":"32","author":"Mohamad 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