Highly prevalent SERPINB7 founder mutation causes pseudodominant inheritance pattern in Nagashima-type palmoplantar keratosis

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. 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.