title: A novel mutation of keratin 9 in a large Chinese family with epidermolytic palmoplantar keratoderma.
abstract: BACKGROUND
  Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant inherited skin disorder characterized by diffuse yellow thickening of the skin of the palms and soles, sharply bordered with erythematous margins. Histologically and ultrastructurally, EPPK presents cytolysis of keratinocytes and abnormal aggregation of tonofilaments in the suprabasal layers of the epidermis. To date, 15 different mutations of the keratin 9 gene (KRT9) have been demonstrated to cause most cases of EPPK.
  
  
  OBJECTIVE
  To identify the KRT9 mutation in a large Chinese family with EPPK.
  
  
  METHODS
  Denaturing high-performance liquid chromatography (DHPLC), DNA sequencing and allele-specific polymerase chain reaction (AS-PCR) were used to screen exon 1 of the KRT9 gene for sequence variations.
  
  
  RESULTS
  The DHPLC elution profiles of the DNA fragments amplified from the affected samples differed from those obtained from unaffected individuals, indicating that a sequence variation existed within the analysed fragment of KRT9. DNA sequencing revealed a novel insertion-deletion mutation in the exon 1 of KRT9, 497delAinsGGCT, resulting in the change of tyrosine(166) to tryptophan and leucine (Y166delinsWL). AS-PCR confirmed the mutation was not a common polymorphism.
  
  
  CONCLUSIONS
  The results suggest the molecular basis of EPPK in this Chinese family and provide further evidence that mutations in the helix initiation motif of keratin 9 underlie Chinese EPPK.
authors.affiliation: Department of Genetics, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, 315211, China.
authors.forename: X-H
authors.initials: XH
authors.lastname: He
authors.forename: X-N
authors.initials: XN
authors.lastname: Zhang
authors.forename: W
authors.initials: W
authors.lastname: Mao
authors.forename: H-P
authors.initials: HP
authors.lastname: Chen
authors.forename: L-R
authors.initials: LR
authors.lastname: Xu
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: X-L
authors.initials: XL
authors.lastname: He
authors.forename: Y-P
authors.initials: YP
authors.lastname: Le
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002681:China / Q000208:ethnology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005091:Exons / Q000235:genetics; D005192:Family Health / Q000208:ethnology; D005260:Female; D006801:Humans; D007633:Keratins / Q000235:genetics*; D007645:Keratoderma, Palmoplantar / Q000208:ethnology / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods
chemical_list: D007633:Keratins