Novel and recurrent mutations in Keratin 5 and 14 in Korean patients with Epidermolysis bullosa simplex

Backgrounds: Epidermolysis bullosa simplex (EBS) is a group of hereditary bullous disorders caused by mutations in the keratin genes KRT5 and KRT14. A significant genotype-phenotype correlation has been noted in previous studies of EBS. Objective: In order to identify additional EBS mutations and elucidate the genotype-phenotype correlations in Korean EBS patients, we performed the first large scale mutational analysis of EBS patients of Korean origin. Methods: We investigated fifteen Korean EBS patients by performing a sequence analysis of the entire coding sequences of KRT5 and KRT14. Results: We identified six novel mutations, four within KRT5 (p.V143F, p.R265P, p.C479X and p.Asn177del), and two within KRT14 (p.R125L and p.L401P). In all, 13 missense, 1 nonsense, and 1 small deletion mutation were found. Five mutations in Dowling-Meara type (K14-p.R125H, K14-p.R125L, K5-E477K, K5-p.C479X and K5-p.Asn177del) were located in the highly conserved ends of the alpha-helical rod domain, the helix initiation (HIP), or helix termination (HTP) peptides of KRT5 and KRT14. Further, seven and three mutations were identified in EBS-generalized type and EBS-localized type, respectively. The positions of the mutations in both subtypes were more widely distributed within the rod domains and in the L12 linker domains of both keratin genes. Conclusions: This study should provide useful data and enhance our understanding of the EBS genotype-phenotype relationship. The genotype-phenotype correlation in Korean EBS patients was similar to previous studies performed in other ethnic groups. Lastly, our results confirmed that the mutational location in KRT5 or KRT14 is the most important factor in determining the phenotype severity.