{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:50:46Z","timestamp":1787323846264,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073422"],"award-info":[{"award-number":["82073422"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273504"],"award-info":[{"award-number":["82273504"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874239"],"award-info":[{"award-number":["81874239"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Palmoplantar keratoderma (PPK) is a heterogeneous group of skin diseases, characterised by excessive keratinization and hyperplasia of the palms and soles. However, accurate molecular diagnosis remains challenging due to the low prevalence of hereditary forms. This study analysed the phenotype and genotype distribution in a large cohort of Chinese patients with PPK, aiming to clarify the genetic aetiology and genotype\u2013phenotype correlations. We further validated the pathogenicity of biallelic\n                    <jats:italic>SERPINA12<\/jats:italic>\n                    variants identified in four patients. A total of 424 patients with PPK were enrolled from 2010 to 2023. Of these, 97.6% (414\/424) presented with diffuse PPK, predominantly Nagashima\u2010type PPK (NPPK), with rare cases of Olmsted, Meleda and Bothnia types. Focal PPK accounted for 1.4%, with less than 1% for striate and punctate types, respectively. Genetic testing was performed in 380 patients. Overall, 328 patients harboured pathogenic or likely pathogenic (P\/LP) variants to achieve definite molecular diagnosis; none carried only variants of uncertain significance (VUS) and the remaining 52 patients had no candidate disease\u2010associated variants identified. All patients underwent testing with an in\u2010house customised\n                    <jats:italic>SERPINB7<\/jats:italic>\n                    gene hotspot panel test for c.796C&gt;T, c.522_523insT, c.806_818delinsT and c.650_653delCTGT variants. In 80% (304\/380) patients, hotspot variants in\n                    <jats:italic>SERPINB7<\/jats:italic>\n                    were identified, with c.796C&gt;T (77%) and c.522_523insT (16%) being the most frequent. Patients not diagnosed with a hotspot variant further underwent whole\u2010exome sequencing (WES), which identified confirmed pathogenic (P) or likely pathogenic (LP) variants in\n                    <jats:italic>TRPV3<\/jats:italic>\n                    (c.1246C&gt;T, c.1703G&gt;A, c.1247G&gt;A),\n                    <jats:italic>AQP5<\/jats:italic>\n                    (c.530\u2009T&gt;A, c.367A&gt;T),\n                    <jats:italic>SLURP1<\/jats:italic>\n                    (c.154A&gt;G),\n                    <jats:italic>KRT9<\/jats:italic>\n                    (c.1373\u2009T&gt;C),\n                    <jats:italic>KRT6A<\/jats:italic>\n                    (c.947G&gt;C) and\n                    <jats:italic>KRT16<\/jats:italic>\n                    (c.379C&gt;T). In addition, three recurrent\n                    <jats:italic>SERPINA12<\/jats:italic>\n                    variants were identified, enriching the gene spectrum of diffuse PPK. This study established the largest cohort of patients with\n                    <jats:italic>SERPINB7<\/jats:italic>\n                    variants reported to date, identifying that NPPK is the predominant subtype among Chinese populations. Variants in\n                    <jats:italic>SERPINA12<\/jats:italic>\n                    are likely correlated with diffuse palmoplantar keratoderma, consistent with the clinical manifestations of NPPK. Additionally, a diagnostic panel targeting ancestral\n                    <jats:italic>SERPINB7<\/jats:italic>\n                    founder variants would markedly improve the molecular diagnostic yield in Chinese patients.\n                  <\/jats:p>","DOI":"10.1111\/exd.70311","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T18:10:46Z","timestamp":1782929446000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Large\u2010Scale Cohort Study on the Genetic and Phenotypic Findings of Palmoplantar Keratodermas in the Chinese Population"],"prefix":"10.1111","volume":"35","author":[{"given":"Xinyi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Dermatology Minhang Hospital, Fudan University  Shanghai China"},{"name":"Department of Dermatology Huashan Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Dermatology Children's Hospital of Fudan University, National Children's Medical Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Children's Hospital of Fudan University, National Children's Medical Center  Shanghai China"},{"name":"Department of Dermatology Anhui Provincial Children's Hospital  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5298-3171","authenticated-orcid":false,"given":"Yumeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Xinhua Hospital Shanghai Jiaotong University School of Medicine  Shanghai China"},{"name":"Institute of Dermatology Shanghai Jiaotong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyang","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Reliable Medical Group Co. Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongsong","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Dermatology Anhui Provincial Children's Hospital  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyao","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Dermatology Anhui Provincial Children's Hospital  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoyu","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Dermatology Children's Hospital of Fudan University, National Children's Medical Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology Huashan Hospital of Fudan University  Shanghai 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