title: Mutations in the keratin 9 gene in Pakistani families with epidermolytic palmoplantar keratoderma.
abstract: BACKGROUND
  Keratins are heteropolymeric proteins that form the intermediate filament cytoskeleton in epithelial cells. The common basic structure of all keratins is organized in a central α-helical rod domain flanked by nonhelical, variable head and tail regions. Most mutations in keratins are found in the central α-helical rod domain. Keratin 9 (K9) is expressed only in the suprabasal layers of palmoplantar epidermis. Mutations in the keratin 9 gene (KRT9) have been shown to cause epidermolytic palmoplantar keratoderma (EPPK; OMIM 144200), an autosomal dominant genodermatosis characterized clinically by diffuse hyperkeratosis limited to the palms and soles, and histologically by epidermolysis in suprabasal layers of the epidermis.
  
  
  OBJECTIVE
  To elucidate the genetic basis of EPPK in five Pakistani families.
  
  
  METHODS
  Using microsatellite markers localized to the areas around the type I keratin gene cluster on chromosome 17q21, genotyping of these families was performed, followed by sequencing of the KRT9 gene.
  
  
  RESULTS
  The analysis resulted in the identification of two novel (p.M157K and p.Y454H) and two recurrent (p.M157T and p.R163Q) mutations in the KRT9 of all five families. All mutations occurred within the highly conserved helix initiation or termination motif of K9.
  
  
  CONCLUSIONS
  The affected members of all five families possess mutations in the KRT9 gene that severely affect heterodimer formation with the type II keratin partner. The results of our study further underscore the crucial role of K9 protein in the palmoplantar epidermis.
authors.affiliation: Department of Dermatology, Columbia University, New York, NY 10032, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Shimomura
authors.forename: M
authors.initials: M
authors.lastname: Wajid
authors.forename: J
authors.initials: J
authors.lastname: Weiser
authors.forename: L
authors.initials: L
authors.lastname: Kraemer
authors.forename: A M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D000595:Amino Acid Sequence; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D053534:Keratin-9 / Q000235:genetics*; D053546:Keratoderma, Palmoplantar, Epidermolytic / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D010154:Pakistan / Q000208:ethnology; D010375:Pedigree; D016415:Sequence Alignment
chemical_list: C507440:KRT9 protein, human; D053534:Keratin-9