Two novel mutations of SERPINB7 in eight cases of Nagashima-type palmoplantar keratosis in the Chinese population.

Nagashima-type palmoplantar keratosis (NPPK) is a diffuse, autosomal recessive, and non-epidermolytic palmoplantar keratosis caused by mutations in the SERPINB7 gene, a member of the serine protease inhibitor superfamily. Genetic studies and case reports suggest that NPPK is the most common palmoplantar keratosis in East Asia but rare in Western countries. This study reports eight NPPK patients in seven pedigrees of the Chinese Han ethnicity with two novel (c.530T>C and c.643A>G) and two recurrent mutations (c.796C>T and c.455G>T) in SERPINB7. The diagnosis of NPPK is now well-defined because of the typical manifestations and pathogenic gene tests. However, its pathomechanism is still obscure, and treatment remains a challenge. This study reviewed all 15 pathogenic mutations and related data in the 1000 Genomes Project to elucidate the founder effect of SERPINB7. Also, several latest cases of NPPK in areas outside East Asia are presented, including France, Finland, and Thailand. Further clinical investigation and genetic studies are crucial for identifying the pathomechanism of NPPK. Also, large-scale control studies are required to determine the safety and curative effects of available therapies.