Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema

Nat Genet. 2007 May;39(5):650-4. doi: 10.1038/ng2020. Epub 2007 Apr 8.


We recently reported two common filaggrin (FLG) null mutations that cause ichthyosis vulgaris and predispose to eczema and secondary allergic diseases. We show here that these common European mutations are ancestral variants carried on conserved haplotypes. To facilitate comprehensive analysis of other populations, we report a strategy for full sequencing of this large, highly repetitive gene, and we describe 15 variants, including seven that are prevalent. All the variants are either nonsense or frameshift mutations that, in representative cases, resulted in loss of filaggrin production in the epidermis. In an Irish case-control study, the five most common European mutations showed a strong association with moderate-to-severe childhood eczema (chi2 test: P = 2.12 x 10(-51); Fisher's exact test: heterozygote odds ratio (OR) = 7.44 (95% confidence interval (c.i.) = 4.9-11.3), and homozygote OR = 151 (95% c.i. = 20-1,136)). We found three additional rare null mutations in this case series, suggesting that the genetic architecture of filaggrin-related atopic dermatitis consists of both prevalent and rare risk alleles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Codon, Nonsense / genetics
  • Dermatitis, Atopic / genetics*
  • Epidermis / metabolism
  • Filaggrin Proteins
  • Frameshift Mutation / genetics
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Humans
  • Ichthyosis Vulgaris / genetics*
  • Intermediate Filament Proteins / genetics*
  • Intermediate Filament Proteins / metabolism
  • Ireland
  • Molecular Sequence Data
  • Sequence Analysis, DNA
  • White People


  • Codon, Nonsense
  • FLG protein, human
  • Filaggrin Proteins
  • Intermediate Filament Proteins

Associated data

  • RefSeq/NM_002016