title: Wide spectrum of filaggrin-null mutations in atopic dermatitis highlights differences between Singaporean Chinese and European populations.
abstract: BACKGROUND
  Null mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris (IV) and predispose to atopic dermatitis (AD). Cohort studies in Europe and Japan have reported an FLG mutation carrier frequency of between 14% and 56%, but the prevalent European FLG mutations are rare or absent in Chinese patients with IV and AD.
  
  
  OBJECTIVE
  To investigate further the spectrum of FLG-null mutations in Chinese patients and to compare it with that in other populations.
  
  
  METHODS
  We conducted comprehensive FLG genetic analysis in a discovery cohort of 92 Singaporean Chinese individuals with IV and/or moderate-to-severe AD. All detected FLG mutations were then screened in a cohort of 425 patients with AD and 440 normal controls. Results In total, 22 FLG-null mutations, of which 14 are novel, were identified in this study; the combined null FLG genotype of 17 mutations detected in cases and controls showed strong association with AD [Fisher's exact test; P = 5·3 × 10⁻⁹; odds ratio (OR) 3·3], palmar hyperlinearity (Fisher's exact test; P = 9·0 × 10⁻¹⁵; OR 5·8), keratosis pilaris (Fisher's exact test; P = 0·001; OR 4·7) and with increased severity of AD (permutation test; P = 0·0063).
  
  
  CONCLUSIONS
  This study emphasizes the wider genetic landscape of FLG-null mutations in Asia that is slowly emerging.
authors.affiliation: Institute of Medical Biology, Immunos, 8A Biomedical Grove, Singapore 138648, Singapore.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: J E A
authors.initials: JE
authors.lastname: Common
authors.forename: R L
authors.initials: RL
authors.lastname: Haines
authors.forename: A
authors.initials: A
authors.lastname: Balakrishnan
authors.forename: S J
authors.initials: SJ
authors.lastname: Brown
authors.forename: C S M
authors.initials: CS
authors.lastname: Goh
authors.forename: H J
authors.initials: HJ
authors.lastname: Cordell
authors.forename: A
authors.initials: A
authors.lastname: Sandilands
authors.forename: L E
authors.initials: LE
authors.lastname: Campbell
authors.forename: K
authors.initials: K
authors.lastname: Kroboth
authors.forename: A D
authors.initials: AD
authors.lastname: Irvine
authors.forename: D L M
authors.initials: DL
authors.lastname: Goh
authors.forename: M B Y
authors.initials: MB
authors.lastname: Tang
authors.forename: H P
authors.initials: HP
authors.lastname: van Bever
authors.forename: Y C
authors.initials: YC
authors.lastname: Giam
authors.forename: W H I
authors.initials: WH
authors.lastname: McLean
authors.forename: E B
authors.initials: EB
authors.lastname: Lane
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D003876:Dermatitis, Atopic / Q000208:ethnology / Q000235:genetics*; D005260:Female; D000091344:Filaggrin Proteins; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D016112:Ichthyosis Vulgaris / Q000235:genetics; D007223:Infant; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012846:Singapore; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins