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.
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.
Authors: Richard M Silverman; Erin E Cummings; Linda P O'Reilly; Mark T Miedel; Gary A Silverman; Cliff J Luke; David H Perlmutter; Stephen C Pak Journal: Genetics Date: 2015-03-18 Impact factor: 4.562