Novel loss-of-function variants in filaggrin exon 3 in patients with severe atopic dermatitis

The strongest genetic risk for atopic dermatitis (AD) is variants in the filaggrin gene (FLG). FLG encodes a large protein called profilaggrin, i.e. the precursor of filaggrin which plays a multifaceted role in maintaining skin barrier function by contributing to hydration via natural moistur- izing factor formation, corneocyte structural integrity, pH regulation, antimicrobial defence, and lipid barrier forma- tion [1]. FLG consists of 2 introns and 3 exons. The third exon is the largest and the chief coding element. The iden- tification of causative variants is challenging, due to high sequence homology within the 10 to 12 tandem repeats [2]. The primary objective of this study is to assess the variant frequency of FLG in patients with severe AD vs. healthy individuals.