Abstract
Serine protease inhibitor B7 (SERPINB7) mutations have been reported to cause Nagashima-type palmoplantar keratosis (NPPK), but their biological effects are largely unknown. We conducted whole-exome sequencing and identified a c.796C>T (p.Arg266Ter) mutation in SERPINB7 in a Chinese pedigree, which presented as an autosomal recessive inheritance pattern. We assessed the function of SERPINB7 in homozygous and heterozygous mutation carriers, and the results suggested that the single c.796C>T mutation may alter the subcellular localization of SERPINB7. One of the homozygous mutation patients (II-3) was treated with ixekizumab and showed moderate improvement in keratinization. In addition, we analysed the spatiotemporal expression of serpinb1l1 and serpinb1l3, the zebrafish homologue of human SERPINB7, which is expressed in larvae and adults. In larvae, both serpinb1l1 and serpinb1l3 were expressed in the digestive tract. Then, we performed RT-PCR on adult fins based on similarity to the site of NPPK expression in humans and found that the genes were expressed in five fins (pectoral, pelvic, dorsal, anal and caudal) of the zebrafish distal extremity. Taken together, our results demonstrated that the single c.796C>T (p.Arg266Ter) mutation may alter the location of SERPINB7-encoded protein in the skin, while zebrafish SERPINB7 homologue was expressed in adult fins. These findings will enable us to construct knock-out models to explore the pathogenesis of palmoplantar keratosis.