The molecular pathology of progressive symmetric erythrokeratoderma: a frameshift mutation in the loricrin gene and perturbations in the cornified cell envelope

Am J Hum Genet. 1997 Sep;61(3):581-9. doi: 10.1086/515518.


The erythrokeratodermas (EKs) are a group of disorders characterized by erythematous plaques associated with variable features that include palmoplantar keratoderma. One type of EK is known as "progressive symmetric erythrokeratoderma" (PSEK). We studied members of a family of Japanese origin in which the index case with PSEK had had well-demarcated nonmigratory erythematous plaques on her extremities since birth. Sequence determination of the loricrin gene revealed an insertion of a C following nucleotide 709. The mutation results in a frameshift that changes the terminal 91 amino acids in the wild-type polypeptide into missense amino acids and adds 65 additional residues. This further implicates loricrin defects in the pathogenesis of disorders with palmoplantar keratoderma and pseudoainhum.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Chromosomes, Human, Pair 1 / genetics
  • DNA Mutational Analysis
  • Dermatitis, Exfoliative / genetics*
  • Dermatitis, Exfoliative / pathology
  • Epidermis / pathology
  • Epidermis / ultrastructure
  • Female
  • Frameshift Mutation / genetics*
  • Humans
  • Japan
  • Keratosis / genetics*
  • Keratosis / pathology
  • Male
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics*
  • Middle Aged
  • Molecular Sequence Data
  • Skin / chemistry
  • Skin / pathology


  • Membrane Proteins
  • loricrin