Missing links: Weber-Cockayne keratin mutations implicate the L12 linker domain in effective cytoskeleton function

Nat Genet. 1993 Nov;5(3):294-300. doi: 10.1038/ng1193-294.


We have identified mutations in keratins K5 (Arg331Cys) and K14 (Val270Met) in two kinships affected by the dominantly-inherited skin blistering disease, Weber-Cockayne epidermolysis bullosa simplex (EBS-WC). Linkage analysis, DNA sequencing and clinical and ultrastructural analysis are combined to provide the first detailed description of classical EBS-WC. Both phenotypes show similar blistering on trauma, indicating that both mutations compromise the structural resilience of the basal keratinocytes by affecting the keratin cytoskeleton. The location of these mutations in the L12 linker, which bisects the alpha-helical rod region of intermediate filament proteins, identifies another keratin mutation cluster leading to hereditary skin fragility syndromes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Amino Acid Sequence
  • Base Sequence
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Cytoskeleton / chemistry
  • Cytoskeleton / physiology*
  • DNA Primers
  • Epidermolysis Bullosa Simplex / genetics*
  • Female
  • Humans
  • Infant, Newborn
  • Keratins / genetics*
  • Male
  • Microscopy, Electron
  • Molecular Sequence Data
  • Mutation*
  • Phenotype
  • Skin / pathology
  • Skin / ultrastructure


  • DNA Primers
  • Keratins