Novel keratin 14 gene mutations in patients from Hungary with epidermolysis bullosa simplex

Abstract: Mutations in genes keratin 5 ( KRT5 ) and 14 ( KRT14 ) encoding the basal type keratin intermediate filaments have been identified in epidermolysis bullosa simplex (EBS) families and are likely to cause skin fragility. Three novel keratin 14 mutations in cases from the Hungarian Epidermolysis Bullosa Centre are reported. In a 7‐year‐old boy with Dowling‐Meara type EBS (DM‐EBS), who had severe skin symptoms with extended herpetiform blisters, a novel amino acid substitution N123K in keratin 14 had been detected. A 26‐year‐old woman with mild DM‐EBS with prominent palmoplantar hyperkeratosis and without active blister formation had a novel R125G mutation in keratin 14. In a 6‐year‐old girl, with Weber‐Cockayne type EBS (WC‐EBS) with palmoplantar blisters and moderate mental retardation, a novel V133L substitution was detected. Her pedigree showed autosomal dominant mode of inheritance; in the two other families, only the index patients were affected. The N123K and R125G mutations causing DM‐EBS phenotypes are located within the helix initiation motif of the rod domain, whereas the very close V133L mutation underlying the WC‐EBS phenotype is outside of this region. These novel amino acid substitutions provide further information for genotype–phenotype correlation in KRT14 mutations, and demonstrate the first molecular genetic data in EBS patients from Hungary.