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

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 SERPINB 7 , 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 SERPINB 7 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 SERPINB 7 . 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 SERPINB 7 .