Mutation analysis of Filaggrin, SLC25A46, and TMEM232 in Thai patients with atopic dermatitis

Abstract

Atopic dermatitis is a chronic inflammatory skin disease that affects patients’ quality of life. It has complex etiology with genetic and environmental factors. Recently, loss-of-function mutations in the filaggrin gene (FLG) have been identified as its major predisposing factor in some Caucasian and Asian populations. FLG plays an essential role in the terminal differentiation of the epidermis and formation of skin barrier. However, the association between FLG mutations and atopic dermatitis in the Thai population remains unknown. In addition, Genome-wide association study in the Han Chinese population revealed a new susceptibility locus for atopic dermatitis comprising SLC25A46 and TMEM232. Here we investigated the FLG, SLC25A46, and TMEM232 mutations by PCR-sequencing of the entire coding regions of FLG in 48 unrelated Thai individuals with atopic dermatitis. Our modified PCR method helped reduce operating costs and time. Four FLG mutations, p.G526X, p.R1555SfsX1706, p.S1906X, and p.R3982X were identified in four unrelated patients (8.3%). All four mutations have never been previously reported. Several lines of evidence suggest their pathogenicity. We found no pathogenic mutations in SLC25A46 and TMEM232. In summary, for the first time, we reported four FLG novel mutations in Thai atopic dermatitis patients expanding mutational spectrum of FLG and suggested the important role of FLG in Thai patients with atopic dermatitis.