{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T10:51:10Z","timestamp":1761821470064,"version":"3.41.2"},"reference-count":22,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Papilon\u2010Lefevre syndrome (PLS; OMIM 245000) is a rare autosomal recessive disease characterized by aggressive periodontitis and palmoplantar keratoderma. The prevalence of PLS in the general population is one to four cases per million. Although the etiology and pathogenic mechanisms underlying PLS remain largely unclear, existing evidence shows loss\u2010of\u2010function mutations of the <jats:italic>cathepsin C<\/jats:italic> gene (<jats:italic>CTSC<\/jats:italic>; OMIM 602365) could cause PLS. Here we found a novel variant of the <jats:italic>CTSC<\/jats:italic> gene in a Chinese PLS family and predicted the effect of the variant on the physic\u2013chemical characters and tertiary structure of the protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The 1\u20137 coding exons and exon\u2013intron boundaries of <jats:italic>CTSC<\/jats:italic> gene of the proband and her family were amplified and sequenced directly, and Chromas was used to read sequencing files. Furthermore, the PolyPhen\u20102, PROVEAN, and Mutation Taster were utilized to predict the pathogenicity of the variant. Besides, the physic\u2013chemical and structural characters of the protein were analyzed by ProtParam, ProtScale, and SWISS\u2010MODEL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our study identified a novel homozygous variant c.763T&gt;C (p.Cys255Arg) in exon 6 of the <jats:italic>CTSC<\/jats:italic> gene, and it was a likely pathogenic variant as predicted by PolyPhen\u20102, PROVEAN, and Mutation Taster. Moreover, ProtParam and Protscale revealed the variant increased the isoelectric point and hydrophilicity of the protein, and the SWISS\u2010MODEL analysis suggested the variant was located in a critical domain for protein activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study analyzed a Chinese family with PLS and identified a novel missense variant in the <jats:italic>CTSC<\/jats:italic> gene. Besides, this study retrospectively summarized 113 variants of <jats:italic>CTSC<\/jats:italic> in the world and highlighted the features of 27 <jats:italic>CTSC<\/jats:italic> variants in Chinese PLS patients. In addition, this study paid much particular attention to the relationship between <jats:italic>CTSC<\/jats:italic> variants and different phenotypes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1686","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T16:58:29Z","timestamp":1620233909000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A novel missense variant in <i>cathepsin C<\/i> gene leads to PLS in a Chinese patient: A case report and literature review"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0436-8721","authenticated-orcid":false,"given":"Hui","family":"Yu","sequence":"first","affiliation":[{"name":"College of Medical Technology Chengdu University of Traditional Chinese Medicine Chengdu China"},{"name":"Jiangyou People's Hospital Jiangyou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xun","family":"He","sequence":"additional","affiliation":[{"name":"School of Medicine University of Electronic Science and Technology of China Chengdu China"},{"name":"Sichuan Provincial Institute of Dermatology and Venereology Chengdu China"},{"name":"Department of Dermatology Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangqin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Houbin","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine University of Electronic Science and Technology of China Chengdu China"},{"name":"Department of Laboratory Medicine Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital Chengdu China"},{"name":"Sichuan Provincial Key Laboratory for Human Disease Gene Study, Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026) Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhu","family":"Shen","sequence":"additional","affiliation":[{"name":"School of Medicine University of Electronic Science and Technology of China Chengdu China"},{"name":"Sichuan Provincial Institute of Dermatology and Venereology Chengdu China"},{"name":"Department of Dermatology Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Medicine University of Electronic Science and Technology of China Chengdu China"},{"name":"Department of Laboratory Medicine Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital Chengdu China"},{"name":"Sichuan Provincial Key Laboratory for Human Disease Gene Study, Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026) Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqi","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine University of Electronic Science and Technology of China Chengdu China"},{"name":"Department of Laboratory Medicine Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital Chengdu China"},{"name":"Sichuan Provincial Key Laboratory for Human Disease Gene Study, Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026) Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sjbs.2015.06.007"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046688"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.12.927"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.2.88"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2010.03575.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000245341"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-020-05622-0"},{"issue":"2","key":"e_1_2_10_10_1","first-page":"81","article-title":"Two cases of symmetrically familial palmar and plantar hyperkeratosis (Meleda disease) within brother and sister combined with severe dental alterations in both cases","volume":"31","author":"Papillon M. 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