Ichthyosis vulgaris: identification of a defect in synthesis of filaggrin correlated with an absence of keratohyaline granules

J Invest Dermatol. 1985 Mar;84(3):191-4. doi: 10.1111/1523-1747.ep12264813.


Ichthyosis vulgaris is an autosomal dominant disorder of keratinization characterized histologically by absent or reduced keratohyaline granules in the epidermis and mild hyperkeratosis. The basic defect in ichthyosis vulgaris is unknown. We have tested for the presence of filaggrin and its precursor, profilaggrin, in the epidermis of affected and unaffected individuals from 2 families with ichthyosis vulgaris and correlated its presence and relative quantity with ultrastructure findings in the same individuals. Filaggrin was present on stained sodium dodecyl sulfate gels and immunoblots of epidermal proteins from controls and unaffected family members. It was absent from the more severely affected individuals in each family and reduced in intensity in the less severely affected family members. Immunohistology in controls showed localization of filaggrin-related protein in the stratum corneum and within the granular layer. In contrast, tissue from affected individuals showed little or no reaction. Electron microscopic studies showed that keratohyaline granules were absent in 3 severely affected individuals, and reduced in number in the others. The relative amount of keratohyalin by electron microscopy correlated with the amount of filaggrin detectable on immunoblots. The stratum corneum was thicker than in normals but showed the typical "keratin pattern" staining suggesting that filaggrin is not essential for keratin filament aggregation and may have another function in vivo. We have demonstrated that the structural proteins, profilaggrin and filaggrin, are reduced or absent in 5 patients from 2 pedigrees with ichthyosis vulgaris. This biochemical abnormality correlates with the morphologic reduction in the amount of keratohyalin, and with the clinical severity of the disorder.

Publication types

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

MeSH terms

  • Adult
  • Electrophoresis, Polyacrylamide Gel
  • Epidermis / metabolism*
  • Epidermis / pathology
  • Epidermis / ultrastructure
  • Female
  • Histocytochemistry
  • Humans
  • Ichthyosis / genetics
  • Ichthyosis / metabolism*
  • Ichthyosis / pathology
  • Immunoenzyme Techniques
  • Intermediate Filament Proteins / analysis
  • Intermediate Filament Proteins / biosynthesis*
  • Keratins / analysis*
  • Male
  • Protein Precursors / analysis


  • Intermediate Filament Proteins
  • Protein Precursors
  • filaggrin
  • keratohyalin
  • Keratins