Background: Atopic dermatitis (AD) is a highly prevalent chronic inflammatory skin disease that is known to be, at least in part, genetically determined. Mutations in caspase recruitment domain-containing protein 14 (CARD14) have been shown to result in various forms of psoriasis and related disorders. Objective: We aimed to identify rare DNA variants conferring a significant risk for AD through genetic and functional studies in a cohort of patients affected with severe AD. Methods: Whole-exome and direct gene sequencing, immunohistochemistry, real-time PCR, ELISA, and functional assays in human keratinocytes were used. Results: In a cohort of patients referred with severe AD, DNA sequencing revealed in 4 patients 2 rare heterozygous missense mutations in the gene encoding CARD14, a major regulator of nuclear factor kB (NF-kB). A dual luciferase reporter assay demonstrated that both mutations exert a dominant loss-offunction effect and result in decreased NF-kB signaling.

Pancreatic enzyme intolerance, although rare, would be a major problem in the management of patients with CF. Hence, desensitization would be essential and may be accomplished successfully using the protocol described in this report.

No abstract

No abstract