Two novel recessive mutations in KRT14 identified in a cohort of 21 Spanish families with epidermolysis bullosa simplex

Summary Background Basal epidermolysis bullosa simplex (EBS) is a group of blistering geno-dermatoses mostly caused by mutations in the keratin genes, KRT5 and KRT14.Recessive mutations represent about 5% of all EBS mutations, being common andspecific in populations with high consanguinity, where affected patients showsevere phenotypes.Objectives To accomplish the first mutational analysis in patients of Spanish originwith EBS and to delineate a comprehensive genotype–phenotype correlation.Methods Twenty-one EBS families were analysed. Immunofluorescence mapping atthe dermoepidermal junction level was performed on skin biopsies from patients.Mutation screening of the entire coding sequences of KRT5 and KRT14 in genomicDNA was assessed by polymerase chain reaction and direct sequencing.Results KRT5 or KRT14 causative mutations were identified in 18 of the 21 EBSfamilies. A total of 14 different mutations were disclosed, of which 12 weredominant missense mutations and two truncating recessive mutations. Five of the14 mutations were novel including three dominant in KRT5 (p.V186E, p.T321Pand p.A428T) and two recessive in KRT14 (p.K116X and p.K250RfsX8). The twopatients with EBS carrying homozygous recessive mutations were affected bysevere phenotypes and belonged to consanguineous families. All five familieswith the EBS Dowling–Meara subtype carried recurrent mutations affecting thehighly conserved ends of the a-helical rod domain of K5 and K14. The sevenmutations associated with the localized EBS subtype were widely distributedalong the KRT5 and KRT14 genes. Two families with mottled pigmentation carriedthe P25L mutation in KRT5, commonly associated with this subtype.Conclusions This study further confirms the genotype–phenotype correlation estab-lished for EBS in other ethnic groups, and is the first in a Mediterranean country(excluding Israel). This study adds two novel recessive mutations to the worldwiderecord to date, which includes a total of 14 mutations. As in previous reports, therecessive mutations resulted in a lack of keratin K14, giving rise to a generalizedand severe presentation.