{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T14:36:27Z","timestamp":1775918187614,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["23FC1039"],"award-info":[{"award-number":["23FC1039"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JPMJFR210R"],"award-info":[{"award-number":["JPMJFR210R"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP24K02470"],"award-info":[{"award-number":["JP24K02470"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP22H04986"],"award-info":[{"award-number":["JP22H04986"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Autosomal recessive congenital ichthyosis (ARCI) is a rare inherited skin disorder marked by generalised scaling and erythema. Very recently, diseases formerly diagnosed as ichthyosis, including ARCI, have been renamed nonsyndromic epidermal differentiation disorders (nEDDs). Although pathogenic variants in various genes, including <jats:italic>PNPLA1<\/jats:italic>, have been identified as causes, regional and ethnic differences exist in their prevalence. <jats:italic>PNPLA1<\/jats:italic> encodes a unique transacylase essential for acylceramide synthesis, a critical component of the skin barrier. Here, we describe the first reported Japanese case of a <jats:italic>PNPLA1<\/jats:italic>\u2010related nonsyndromic epidermal differentiation disorder (<jats:italic>PNPLA1<\/jats:italic>\u2010nEDD) caused by a homozygous 92\u2010base\u2010pair duplication variant (c.36_127dup, p.Leu43Profs*46) in <jats:italic>PNPLA1<\/jats:italic>. Lipidomic analysis of the stratum corneum revealed marked reductions in \u03c9\u2010<jats:italic>O<\/jats:italic>\u2010acylceramides and protein\u2010bound ceramides, alongside the accumulation of non\u2010acylated ceramides\u2014indicating a failure in acylceramide synthesis. This ceramide profile supports the conclusion that the <jats:italic>PNPLA1<\/jats:italic> duplication causes a loss of function. Our findings emphasise the importance of <jats:italic>PNPLA1<\/jats:italic> in the genetic screening of nEDD cases in Japan, regardless of clinical subtype, due to the absence of genotype\u2013phenotype correlations and to broad phenotypic variability.<\/jats:p>","DOI":"10.1111\/exd.70130","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T07:09:50Z","timestamp":1750662590000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The First Reported Japanese Case of <i>PNPLA1<\/i>\u2010Nonsyndromic Epidermal Differentiation Disorder (<i>PNPLA1<\/i>\u2010<scp>nEDD<\/scp>) Associated With an Unreported 92\u2010Base\u2010Pair Duplication Variant"],"prefix":"10.1111","volume":"34","author":[{"given":"Shiori","family":"Kato","sequence":"first","affiliation":[{"name":"Department of Dermatology Nagoya University Graduate School of Medicine  Nagoya 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Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9904-9623","authenticated-orcid":false,"given":"Michiya","family":"Omi","sequence":"additional","affiliation":[{"name":"Department of Dermatology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6703-3515","authenticated-orcid":false,"given":"Kana","family":"Tanahashi","sequence":"additional","affiliation":[{"name":"Department of Dermatology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7365-947X","authenticated-orcid":false,"given":"Atsushi","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Department of Dermatology Kindai University Hospital  Osaka 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