title: Analysis of filaggrin mutations and expression in corneal specimens from patients with or without atopic dermatitis.
abstract: BACKGROUND
  Filaggrin is expressed in the epidermis and is essential for the maintenance of the epidermal barrier. Null mutations within the filaggrin gene (FLG) lead to a disturbed epidermal barrier and are associated with a significantly increased risk of atopic dermatitis (AD). The association of AD with ocular surface disorders prompted us to speculate that common FLG mutations may be particularly prevalent in AD patients with ocular comorbidities.
  
  
  METHODS
  Corneal buttons and biopsies from AD patients with ocular involvement (n = 11) and from non-atopic patients (n = 9) with a histological diagnosis of keratitis were included in the study. DNA samples obtained from paraffin-embedded corneal specimens were genotyped for the two most common FLG mutations (R501X and 2282del4). Filaggrin protein expression was analysed by immunohistochemistry.
  
  
  RESULTS
  Normal skin and corneal specimens (n = 6) were positive for filaggrin, which could be detected in the stratum corneum of the skin and in the basal epithelial layer of the cornea. Interestingly, all AD corneal specimens as well as the specimens from keratitis patients without AD were negative for filaggrin expression. Genotyping of the FLG mutations R501X and 2282del4 revealed wild-type alleles in all analysed samples.
  
  
  CONCLUSIONS
  The lack of filaggrin expression observed in the analysed corneal specimens from AD patients is not due to the two most common FLG mutations (R501X, 2282del4) but is most likely secondary to inflammation, as all keratitis specimens of non-AD patients showed lack of filaggrin expression as well.
authors.affiliation: University Eye Hospital, University Medical Centre Freiburg, Freiburg im Breisgau, Germany.
authors.forename: Thabo
authors.initials: T
authors.lastname: Lapp
authors.forename: Claudia
authors.initials: C
authors.lastname: Auw-Haedrich
authors.forename: Thomas
authors.initials: T
authors.lastname: Reinhard
authors.forename: Rhiannon
authors.initials: R
authors.lastname: Evans
authors.forename: Elke
authors.initials: E
authors.lastname: Rodríguez
authors.forename: Stephan
authors.initials: S
authors.lastname: Weidinger
authors.forename: Thilo
authors.initials: T
authors.lastname: Jakob
mesh_terms: D000483:Alleles; D003315:Cornea / Q000378:metabolism* / Q000473:pathology; D003876:Dermatitis, Atopic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D000091344:Filaggrin Proteins; D015870:Gene Expression; D060005:Genotyping Techniques; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000473:pathology; D007381:Intermediate Filament Proteins / Q000235:genetics*; D007634:Keratitis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D009154:Mutation
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins