Get access

Wide spectrum of filaggrin-null mutations in atopic dermatitis highlights differences between Singaporean Chinese and European populations


  • Funding sources
    Clinical work at the National Skin Centre is funded by NMRC enabling grant. Filaggrin research in the McLean group is supported by grants from the British Skin Foundation/National Eczema Society, the Medical Research Council and the Wellcome Trust (W.H.I.M., A.S. and S.J.B.). E.B.L.’s group is supported by grants from the Institute of Medical Biology, A*STAR. H.C. is funded by the A*STAR graduate academy.

  • Conflicts of interest
    W.H.I.M. has filed patents on genetic testing and therapy development aimed at the filaggrin gene.

  • H.C. and J.E.A.C. contributed equally to this work.

E. Birgitte Lane.


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.

Objectives  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; = 5·3 × 10−9; odds ratio (OR) 3·3], palmar hyperlinearity (Fisher’s exact test; = 9·0 × 10−15; OR 5·8), keratosis pilaris (Fisher’s exact test; = 0·001; OR 4·7) and with increased severity of AD (permutation test; = 0·0063).

Conclusions  This study emphasizes the wider genetic landscape of FLG-null mutations in Asia that is slowly emerging.