title: New mutations in keratin 1 that cause bullous congenital ichthyosiform erythroderma and keratin 2e that cause ichthyosis bullosa of Siemens.
abstract: The intermediate filaments of epithelial cells are formed by keratins, a family of structurally related proteins, which are expressed in pairs of acidic (type I) and basic (type II) polypeptides in a tissue- and differentiation-specific manner. Mutations in the genes encoding several keratins have been implicated in the pathogenesis of diseases of keratinization. We report molecular analysis of two patients with the rare autosomal dominant disorders bullous congenital ichthyosiform erythroderma (BCIE) and ichthyosis bullosa of Siemens (IBS). Previous studies have shown that these genodermatoses are due to mutations in the KRT1 and KRT2E genes, respectively. We report a new amino acid substitution mutation in codon 155 of KRT1 (valine to aspartic acid) in the conserved H1 domain of the protein in the patient with BCIE. We also report a novel amino acid substitution mutation in codon 192 of KRT2E (asparagine to lysine) in the conserved 1A helix initiation peptide of the protein in the patient with IBS. Our results demonstrate that these mutations are deleterious to keratin filament network stability and lead to specific clinical inherited disorders of keratinization.
authors.affiliation: Department of Cell and Molecular Pathology, St John's Institute of Dermatology, The Guy's, King's College, London, UK. nwhittoc@hgmp.mrc.ac.uk
authors.forename: N V
authors.initials: NV
authors.lastname: Whittock
authors.forename: G H
authors.initials: GH
authors.lastname: Ashton
authors.forename: W A
authors.initials: WA
authors.lastname: Griffiths
authors.forename: R A
authors.initials: RA
authors.lastname: Eady
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
mesh_terms: D000328:Adult; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D017488:Hyperkeratosis, Epidermolytic / Q000235:genetics*; D007633:Keratins / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*
chemical_list: D007633:Keratins