title: Keratin 14 point mutations at codon 119 of helix 1A resulting in different epidermolysis bullosa simplex phenotypes.
abstract: Epidermolysis bullosa simplex is a heterogeneous group of inherited bullous disorders due to mutations in keratins 5 and 14. We report two different mutations in keratin 14 at codon 119 of the helix initiation peptide, each with different phenotypic expression. One, a sporadic case that clinically resembles Dowling-Meara epidermolysis bullosa simplex, resulted from conversion of methionine to threonine (M119T). The other, a multigeneration family with the Koebner phenotype, resulted from a previously unreported methionine to valine substitution (M119V). We suggest that loss of hydrophobicity during conversion of methionine to threonine is responsible for the more severe presentation of the first family, whereas maintenance of the hydrophobic nature of the amino acid with conversion to valine resulted in a less severe variant of epidermolysis bullosa simplex. Although most prior mutations in the highly conserved boundary motif of the alpha-helix have resulted in the Dowling-Meara subtype, our findings confirm that it is not always possible to predict the epidermolysis bullosa simplex severity on the basis of the location of the mutation along the keratin polypeptide. The specific amino acid substitution may be more critical in some cases.
authors.affiliation: Department of Dermatology, St. George Hospital, Sydney, New South Wales, Australia.
authors.forename: R E
authors.initials: RE
authors.lastname: Cummins
authors.forename: S
authors.initials: S
authors.lastname: Klingberg
authors.forename: J
authors.initials: J
authors.lastname: Wesley
authors.forename: M
authors.initials: M
authors.lastname: Rogers
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: D F
authors.initials: DF
authors.lastname: Murrell
mesh_terms: D000293:Adolescent; D001483:Base Sequence / Q000235:genetics; D002648:Child; D003062:Codon; D016110:Epidermolysis Bullosa Simplex / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D053547:Keratin-14; D007633:Keratins / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D017433:Protein Structure, Secondary
chemical_list: D003062:Codon; C507540:KRT14 protein, human; D053547:Keratin-14; D007633:Keratins