title: Severe palmo-plantar hyperkeratosis in Dowling-Meara epidermolysis bullosa simplex caused by a mutation in the keratin 14 gene (KRT14).
abstract: Mutant keratins 5 or 14 are implicated in the etiology of epidermolysis bullosa simplex (EBS). The catalog of mutations has established certain patterns of mutation clusters from which it may be possible, along with associated biochemical data, to predict phenotypic severity. It is becoming apparent that some of these assumptions may now require modification. We report a mutation in the gene encoding keratin 14 (KRT14) that changes the predicted amino acid at position 119, at the start of the helix initiation motif, from methionine to threonine (K14 M119T) in a patient with an EBS Dowling-Meara phenotype with severe palmo-plantar hyperkeratosis. This demonstrates that the three major types of EBS can arise from missense mutations in the same codon. The findings suggest that the specific nature of the missense mutation, in the context of the protein sequence, can contribute far more to the clinical severity than previously thought. The different EBS subtypes should be viewed as gradations of clinical severity rather than distinct genetic diseases.
authors.affiliation: Department of Anatomy and Physiology, University of Dundee, UK.
authors.forename: C S
authors.initials: CS
authors.lastname: Shemanko
authors.forename: J E
authors.initials: JE
authors.lastname: Mellerio
authors.forename: M J
authors.initials: MJ
authors.lastname: Tidman
authors.forename: E B
authors.initials: EB
authors.lastname: Lane
authors.forename: R A
authors.initials: RA
authors.lastname: Eady
mesh_terms: D000328:Adult; D016110:Epidermolysis Bullosa Simplex / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D053547:Keratin-14; D007633:Keratins / Q000235:genetics*; D007645:Keratoderma, Palmoplantar / Q000150:complications* / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D017354:Point Mutation; D012720:Severity of Illness Index; D012867:Skin / Q000648:ultrastructure
chemical_list: C507540:KRT14 protein, human; D053547:Keratin-14; D007633:Keratins