A recurrent missense mutation of keratin 1 gene in a Chinese family with epidermolytic hyperkeratosis (severe palmoplantar hyperkeratosis, type 1)

Background  Epidermolytic hyperkeratosis (EHK) is an autosomal dominantly inherited genodermatosis manifesting with blistering and erythroderma in infancy and widespread hyperkeratosis of the skin, particularly over flexural areas, in adulthood. It can be classified into six clinical phenotypes. Case report  We report the case of a 25‐year‐old man who presented with severe palmoplantar thickening and hyperkeratosis over the flexures for nearly 24 years. Histopathological findings showed characteristic features of EHK, and EHK type PS‐1 (severe palmoplantar hyperkeratosis, type 1) was suspected. Further investigation revealed that his father, sister, and nephew (the son of his sister) were similarly affected. A heterozygous missense mutation in exon 7 of KRT1 (c.1436T>C), resulting in an isoleucine to threonine substitution at codon 479 (designated p.I479T), was detected in all affected individuals within the pedigree. Discussion  Up to now, there has been one sporadic case and one family (including 14 affected individuals) with EHK type PS‐1 reported since DiGiovanna and Bale described 25 patients (from two families) with EHK type PS‐1 out of 51 patients (from 21 families) with EHK. Although the mutation (c.1436T>C) in KRT1 reported here is a recurrent one, it has not been reported in Chinese patients with EHK. It is interesting to note that the same mutation in KRT1 can cause different phenotypes of EHK. Conclusions  We expand the clinical heterogeneity of EHK due to the same mutation (c.1436T>C) in KRT1 and enrich the database of the KRT1 gene mutations underlying EHK in the Chinese population.