Nagashima-Type Palmoplantar Keratosis: A Common Asian Type Caused by SERPINB7 Protease Inhibitor Deficiency

Nagashima-type palmoplantar keratosis (NPPK) was identified as a common form of palmoplantar keratosis in Asian populations, particularly in Japan and China, due to a founder mutation in the SERPINB7 gene. This condition was characterized by mild, non-progressive hyperkeratosis on the palms and soles, extending to the dorsal surfaces of the hands and feet, and was associated with hyperhidrosis and tinea infections. The study highlighted that the c.796C>T mutation in SERPINB7 was prevalent among Asian individuals but absent in non-Asian populations, suggesting a founder effect. NPPK was caused by a loss of protease inhibitory activity of SERPINB7, rather than polymer formation, distinguishing it from other serpinopathies. The research underscored the importance of SERPINB7 in maintaining skin homeostasis by regulating protease activity, and its deficiency led to the clinical manifestations of NPPK.