Highly prevalent SERPINB7 founder mutation causes pseudodominant inheritance pattern in Nagashima‐type palmoplantar keratosis. (22nd September 2014)

• Record Type: Journal Article
• Authors: Mizuno, O.; Nomura, T.; Suzuki, S.; Takeda, M.; Ohguchi, Y.; Fujita, Y.; Nishie, W.; Sugiura, K.; Akiyama, M.; Shimizu, H.
• Is Part Of: British journal of dermatology. Volume 171:Number 4(2014:Oct.)
• Page Start: 847
• Page End: 853
• Publication Date: 2014-09-22
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.13076
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: Background: Nagashima‐type palmoplantar keratosis (NPPK) is a distinct autosomal recessive genodermatosis characterized by diffuse transgressive palmoplantar keratoderma (PPK). Very recently, putative loss‐of‐function mutations in SERPINB7, which encodes a member of the serine protease inhibitor superfamily and is abundantly expressed in the epidermis, have been identified as a cause of NPPK. Objectives: To confirm further the role of SERPINB7 mutations in the pathogenesis of NPPK. Methods: We analysed 10 Japanese families with NPPK using Sanger and/or whole‐exome sequencing. Results: We identified one novel and three recurrent null mutations in SERPINB7 . In all the families, the NPPK trait was inherited in an autosomal recessive manner; in one of the families, there was pseudodominant inheritance, which had not been described in NPPK. Conclusions: These data clearly provide further evidence that NPPK is caused by loss‐of‐function mutations in SERPINB7 . Abstract : What's already known about this topic? Nagashima‐type palmoplantar keratosis (NPPK) is a distinct autosomal recessive genodermatosis characterized by diffuse transgressive palmoplantar keratoderma. Very recently, loss‐of‐function mutations in SERPINB7 have been identified as a cause of NPPK. What does this study add? This study further confirms that NPPK is a distinct clinical entity caused by loss‐of‐function mutations in SERPINB7 . Our results provide the first evidence for pseudodominant inheritance in NPPK.