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

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.

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

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.

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.

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.