Identification of novel and known KRT5 and KRT14 mutations in 53 patients with epidermolysis bullosa simplex: correlation between genotype and phenotype

Background: Basal epidermolysis bullosa simplex (EBS) is a hereditary skin blistering disorder resulting in most cases from missense mutations in the keratin 5 (KRT5) or keratin 14 (KRT14) genes.

Objectives: To identify the underlying mutations in different EBS subtypes and correlate genotype and phenotype.

Methods: Mutation analysis was performed in 53 patients with EBS and their families by direct sequencing of the KRT5 and KRT14 genes.

Results: We identified 39 different mutations, of which 15 have not been published previously. Three novel deletion/insertion mutations, among them one in-frame duplication, were associated with the rare phenotype of EBS with mottled pigmentation. We identified for the first time a patient with compound heterozygosity for KRT5 mutations causing Dowling-Degos disease and EBS.

Conclusions: Identification of novel mutations and genotype-phenotype correlations in EBS allow improved understanding of disease pathogenesis as well as better patient management.