title: Two cases of primarily palmoplantar keratoderma associated with novel mutations in keratin 1.
abstract: Mutations in keratin 1 were initially described in the classical form of bullous congenital ichthyosiform erythroderma (also known as epidermolytic hyperkeratosis). More recently the range of phenotypes associated with mutations in this gene has been extended to include annular ichthyosiform erythroderma and mild epidermolytic palmoplantar keratoderma. Here we present two novel mutations in the keratin 1 gene (KRT1): a 5' donor splice site mutation in exon 1 (591 + 2T > A) that predicts a 22 amino acid in-frame deletion in the keratin 1 1A domain; and an in-frame deletion in exon 7 (1376del24) that predicts a foreshortened 2B coiled-coil domain of keratin 1. In each case these mutations are associated with palmoplantar keratoderma and mild ichthyosis, largely limited to the flexural areas. These mutations appear to have a less damaging effect than previously reported mis-sense mutations sited in the helix boundary motifs. This report extends the range of phenotypes associated with mutations in KRT1.
authors.affiliation: Human Genetics Unit, University of Dundee, Ninewells Hospital & Medical School, Dundee, U.K.
authors.forename: Ana
authors.initials: A
authors.lastname: Terron-Kwiatkowski
authors.forename: Amy S
authors.initials: AS
authors.lastname: Paller
authors.forename: John
authors.initials: J
authors.lastname: Compton
authors.forename: David J
authors.initials: DJ
authors.lastname: Atherton
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
authors.forename: Alan D
authors.initials: AD
authors.lastname: Irvine
mesh_terms: D000595:Amino Acid Sequence; D005091:Exons; D005260:Female; D006801:Humans; D007633:Keratins / Q000737:chemistry / Q000235:genetics*; D007645:Keratoderma, Palmoplantar / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: D007633:Keratins