Mapping of the associated phenotype of an absent granular layer in ichthyosis vulgaris to the epidermal differentiation complex on chromosome 1

Exp Dermatol. 2002 Dec;11(6):518-26. doi: 10.1034/j.1600-0625.2002.110604.x.


Ichthyosis vulgaris (IV) is a mild to severe scaling disorder of uncertain etiology estimated to affect as many as 1 : 250 in the population. Family studies have shown that in many cases IV follows an autosomal dominant inheritance pattern, but gene mapping studies have not been reported. To investigate the genetic basis for inherited IV, we have performed gene linkage studies in two multigenerational families where affected individuals have clinical features of IV but distinct histological features. The epidermis in this disorder characteristically displays non-specific orthohyperkeratosis. Notably, a subset of IV patients with a reduced or absent granular epidermal layer (AGL) have been reported, and decreased filaggrin levels have been described in others. The prominent role of profilaggrin in human keratohyalin suggests that defects in the gene for profilaggrin (FLG), its processing of profillagrin to filaggrin, or a gene involved in profilaggrin regulation may underlie or modify the pathology in IV. Family 1 had seven individuals with IV, severe heat intolerance and epidermis with 1-3 granular layers (consistent with normal epidermal histology). Ichthyosis vulgaris in this family did not segregate with FLG or other genes in the epidermal differentiation complex. In contrast, five of the six IV patients in Family 2, all siblings, had epidermis with no granular layer. Significant evidence was obtained for linkage of IV with the associated AGL phenotype to the epidermal differentiation complex (which includes FLG) assuming either a recessive (max Lod 3.4) or dominant (max Lod 3.6) inheritance model. Sequence analysis of FLG did not reveal a mutation in the amino or carboxyl terminal portions of the coding sequence adjacent to filaggrin repeats. The AGL may represent an endophenotype for IV, and the presence of a modifier of IV pathology at this locus is discussed.

MeSH terms

  • Adult
  • Amino Acid Sequence / genetics
  • Cell Differentiation / genetics
  • Chromosome Mapping*
  • Chromosomes, Human, Pair 1*
  • Epidermis / pathology*
  • Female
  • Genetic Linkage
  • Humans
  • Ichthyosis Vulgaris / genetics*
  • Ichthyosis Vulgaris / pathology*
  • Intermediate Filament Proteins / genetics
  • Male
  • Pedigree
  • Phenotype
  • Protein Precursors / genetics


  • Intermediate Filament Proteins
  • Protein Precursors
  • filaggrin