A prospective study of filaggrin null mutations in keratoconus patients with or without atopic disorders.

Atopic dermatitis (AD) is significantly associated with keratoconus (KC). An inherited component for KC has been suggested. Filaggrin (FLG) mutations are a strong genetic risk factor for AD. Since filaggrin is also expressed in the corneal epithelium, we hypothesized a common aetiology for ichthyosis vulgaris (IV), AD and KC. We examined the prevalence of AD and IV in a KC population. We also studied the expression of filaggrin in normal and KC cornea and analysed 2 prevalent loss-of-function FLG alleles (R501X and 2282del4) in a KC population. Finally we examined whether the population with KC and FLG mutations had specific clinical characteristics. Of 89 KC patients, 38 had current or a history of AD and/or IV. Five patients were carriers of at least 1 FLG mutant allele and had a clinical diagnosis of AD and IV with a severer KC. The low frequency of FLG mutations is surprising since 42.7% of our KC population had AD associated or not with IV; the expected frequency would have been 12-15%, based on our previous studies. Further studies are required to look at other possible FLG mutations or other candidate genes.