{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T17:33:00Z","timestamp":1772213580080,"version":"3.50.1"},"reference-count":16,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82003327"],"award-info":[{"award-number":["82003327"]}],"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":["82073423"],"award-info":[{"award-number":["82073423"]}],"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":["81872515"],"award-info":[{"award-number":["81872515"]}],"id":[{"id":"10.13039\/501100001809","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":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Epidermolytic palmoplantar keratoderma (EPPK) is characterized by diffuse hyperkeratosis affecting palms and soles with suprabasal epidermolysis or vacuolar degeneration histopathologically. The disorder is caused by heterozygous mutations in <jats:italic>KRT9<\/jats:italic> or <jats:italic>KRT1<\/jats:italic>. Dominant\u2010negative mutations in <jats:italic>KRT1<\/jats:italic> could also result in epidermolytic ichthyosis with EPPK, a more severe entity affecting the entire body.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the genetic basis and pathogenesis of two unrelated patients with EPPK and knuckle pads, both of whom were born to consanguineous parents of Chinese origin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Next\u2010generation sequencing was applied to the two patients using genomic DNA extracted from peripheral blood. Quantitative reverse\u2010transcriptase polymerase chain reaction (qRT\u2010PCR), immunofluorescence (IF) staining and Western blot (WB) were employed to evaluate mRNA and protein expression level. Ultrastructural changes of skin lesion were analysed using transmission electron microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two novel homozygous mutations, c.457C&gt;T (p.Gln153*) and c.33C&gt;G (p.Tyr11*) in <jats:italic>KRT1<\/jats:italic>, were identified in patients 1 and 2 respectively. The nonsense mutations were predicted to result in nonsense\u2010mediated mRNA decay and absence of keratin 1, which was confirmed in the skin lesions from patient 1. Upregulated keratin 2 was detected both in the affected and unaffected skin samples from patient 1, while the protein abundance and distribution pattern of keratin 10 remained unchanged. An aberrant and clumped staining pattern of keratin 9 was noted in the palmar skin of patient 1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Homozygous \u2018knockout\u2019 mutations in <jats:italic>KRT1<\/jats:italic> resulted in EPPK with knuckle pads rather than epidermolytic ichthyosis. We speculated that sparing of non\u2010acral skin might be due to compensatory effect of keratin 2 upregulation by forming heterodimer with keratin 10.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.18189","type":"journal-article","created":{"date-parts":[[2022,5,1]],"date-time":"2022-05-01T12:24:51Z","timestamp":1651407891000},"page":"1857-1862","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Nonsense mutations in <scp><i>KRT1<\/i><\/scp> caused recessive epidermolytic palmoplantar keratoderma with knuckle pads"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2394-1896","authenticated-orcid":false,"given":"R.","family":"Mo","sequence":"first","affiliation":[{"name":"Dermatology Hospital Southern Medical University  Guangzhou China"},{"name":"Department of Dermatology Peking University First Hospital Beijing Key Laboratory of Molecular Diagnosis on Dermatoses and National Clinical Research Center for Skin and Immune Diseases  Beijing China"},{"name":"Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3413-8684","authenticated-orcid":false,"given":"M.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Dermatology Xiamen Chang Gung Hospital  Xiamen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology Peking University First Hospital Beijing Key Laboratory of Molecular Diagnosis on Dermatoses and National Clinical Research Center for Skin and Immune Diseases  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Dermatology Peking University First Hospital Beijing Key Laboratory of Molecular Diagnosis on Dermatoses and National Clinical Research Center for Skin and Immune Diseases  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Wang","sequence":"additional","affiliation":[{"name":"Dermatology Hospital Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9323-2035","authenticated-orcid":false,"given":"Z.","family":"Lin","sequence":"additional","affiliation":[{"name":"Dermatology Hospital Southern Medical University  Guangzhou China"},{"name":"Department of Dermatology Peking University First Hospital Beijing Key Laboratory of Molecular Diagnosis on Dermatoses and National Clinical Research Center for Skin and Immune Diseases  Beijing China"},{"name":"Department of Dermatology Xiamen Chang Gung Hospital  Xiamen 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