title: Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis.
abstract: BACKGROUND
  Filaggrin is a key protein involved in skin barrier function. Recently, mutations in the filaggrin gene, FLG, were identified in European families with ichthyosis vulgaris (IV) and shown to be an important predisposing factor for atopic dermatitis (AD).
  
  
  OBJECTIVE
  To study the role of FLG mutations in IV/AD in Japan.
  
  
  METHODS
  The known filaggrin mutations were studied by genotyping and new mutations identified by DNA sequencing.
  
  
  RESULTS
  The European-specific mutations R501X and 2282del4 were absent from 253 Japanese individuals. We therefore sequenced the FLG gene in 4 Japanese families with IV and identified 2 novel mutations, 3321delA and S2554X. Immunohistologic and ultrastructural observations indicated that both truncation mutations lead to a striking reduction of keratohyalin granules in the epidermis. We screened 143 Japanese patients with AD for these FLG null mutations and identified them in 8 patients with AD (5.6%), including S2554X in 6 patients (4.2%) and 3321delA in 2 patients (1.4%). Both null variants were absent from 156 unrelated Japanese nonatopic and nonichthyotic controls, giving a significant statistical association between the FLG mutations and AD (chi(2)P value, .0015). This is the first report of FLG mutations in a non-European population.
  
  
  CONCLUSIONS
  Our data indicate that FLG mutations in Japan are unique from those found in European-origin populations.
  
  
  CONCLUSIONS
  Filaggrin null variants are also significant predisposing factors for AD in Japan and, on the basis of the recent European studies, may predict a more severe and persistent form of atopy.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Nomura
authors.forename: Aileen
authors.initials: A
authors.lastname: Sandilands
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
authors.forename: Haihui
authors.initials: H
authors.lastname: Liao
authors.forename: Alan T
authors.initials: AT
authors.lastname: Evans
authors.forename: Kaori
authors.initials: K
authors.lastname: Sakai
authors.forename: Mitsuhito
authors.initials: M
authors.lastname: Ota
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sugiura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.forename: Colin N A
authors.initials: CN
authors.lastname: Palmer
authors.forename: Frances J D
authors.initials: FJ
authors.lastname: Smith
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D003876:Dermatitis, Atopic / Q000209:etiology / Q000235:genetics*; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D016112:Ichthyosis Vulgaris / Q000235:genetics*; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins