Genotype-phenotype associations in filaggrin loss-of-function mutation carriers

Contact Dermatitis. 2013 Mar;68(3):149-55. doi: 10.1111/j.1600-0536.2012.02171.x.

Abstract

Background: Loss-of-function mutations in the filaggrin gene (FLG) have been reported to be associated with specific phenotypic characteristics such as hyperlinearity and keratosis pilaris.

Objectives: To study phenotypic features in patients with occupational irritant contact eczema of the hands in relation to FLG loss-of-function mutations.

Materials and methods: In a prospective cohort study, genotype was determined for 459 study subjects for four FLG null alleles, and investigated for selected history, clinical and laboratory features.

Results: Overall, 68 patients showed a mutation in the FLG alleles R501X, R2447X, S3247X, and/or 2282del4. Flexural eczema, xerosis cutis, pityriasis alba, dirty neck, pulpitis sicca, hyperlinear palms, keratosis pilaris and family history of eczema were positively associated with FLG mutations (p < 0.05). Although we observed a statistically significant correlation with higher serum IgE in FLG mutation carriers, allergic rhinoconjunctivitis and allergic asthma were not over-represented in this group.

Conclusion: This study shows further genotype-phenotype correlations in patients with occupational irritant contact eczema and FLG mutation carrier status. These features may help to identify those with FLG mutations on a specific phenotype basis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics
  • Adolescent
  • Adult
  • Aged
  • Cohort Studies
  • Darier Disease / genetics
  • Dermatitis, Irritant / genetics*
  • Dermatitis, Occupational / genetics*
  • Eyebrows / abnormalities
  • Female
  • Filaggrin Proteins
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Hyperpigmentation / genetics
  • Hypopigmentation / genetics
  • Immunoglobulin E / blood
  • Intermediate Filament Proteins / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Prospective Studies
  • Young Adult

Substances

  • FLG protein, human
  • Filaggrin Proteins
  • Intermediate Filament Proteins
  • Immunoglobulin E

Supplementary concepts

  • Burnett Schwartz Berberian syndrome