title: A missense mutation in the rod domain of keratin 14 associated with recessive epidermolysis bullosa simplex.
abstract: Epidermolysis bullosa simplex (EBS) is a group of epidermal blistering diseases almost invariably transmitted as a dominant trait, which has recently been shown to arise from mutations in keratins 14 and 5 (K14 and K5). We describe a family with recessive EBS in which the disease is tightly linked to the substitution of the highly conserved glutamic acid-144 to alanine in the first helical segment of the rod domain of keratin 14. In contrast, linkage with keratin 5 was excluded. The loss of an ionic interaction with keratin 5 is likely to affect K14-K5 heterodimer formation. Our data suggest that this mutation underlies EBS in our family, and that mutations in keratin genes may impair the mechanical integrity of basal keratinocytes in a recessive as well as dominant fashion.
authors.affiliation: Laboratoire de Génétique moléculaire, INSERM U.91, Hôpital Henri Mondor, Créteil, France.
authors.forename: A
authors.initials: A
authors.lastname: Hovnanian
authors.forename: E
authors.initials: E
authors.lastname: Pollack
authors.forename: L
authors.initials: L
authors.lastname: Hilal
authors.forename: A
authors.initials: A
authors.lastname: Rochat
authors.forename: C
authors.initials: C
authors.lastname: Prost
authors.forename: Y
authors.initials: Y
authors.lastname: Barrandon
authors.forename: M
authors.initials: M
authors.lastname: Goossens
mesh_terms: D000409:Alanine; D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D017124:Conserved Sequence; D017931:DNA Primers; D004820:Epidermolysis Bullosa / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D008040:Genetic Linkage; D018698:Glutamic Acid; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D007633:Keratins / Q000737:chemistry / Q000235:genetics*; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary; D012867:Skin / Q000378:metabolism / Q000473:pathology
chemical_list: D017931:DNA Primers; D046911:Macromolecular Substances; D018698:Glutamic Acid; D007633:Keratins; D000409:Alanine