Loss-of-function mutations within the filaggrin gene and atopic dermatitis

Hiroshi Kawasaki, Akiharu Kubo, Takashi Sasaki, Masayuki Amagai

Research output: Chapter in Book/Report/Conference proceedingChapter

20 Citations (Scopus)


Atopic dermatitis (AD) is a chronic relapsing eczematous skin disorder that is frequently associated with elevated serum IgE levels and a personal or family history of AD, allergic rhinitis and/or asthma. Filaggrin is a major constituent of the stratum corneum (SC) and contributes to keratin filament aggregation. Its breakdown products form natural moisturizing factor, which plays a central role in hydration of the SC. Sequence analysis and epidemiological studies indicate that loss-of-function mutations in the filaggrin gene known to cause the autosomal dominant scaly skin disorder ichthyosis vulgaris are major genetic predisposing factors of AD. Mutations in filaggrin are also associated with atopic asthma. These findings established the 'filaggrin hypothesis,' which states that AD can be triggered by the chronic exposure of barrier-disrupted skin to percutaneous antigens due to abnormalities in filaggrin. In this chapter, we summarize the genome-wide screening of AD susceptibility loci, filaggrin biochemistry and recent epidemiological studies on filaggrin mutations and allergic diseases. We also summarize recent advances in the study of skin barrier mechanisms and filaggrin-associated skin barrier abnormalities in animal models. Taken together, these findings provide novel perspectives on the pathophysiology of AD and effective therapeutic methods for the treatment and/or prevention of AD through the modification of skin barrier dysfunction.

Original languageEnglish
Title of host publicationPathogenesis and Management of Atopic Dermatitis
EditorsTetsuo Shiohara
Number of pages12
Publication statusPublished - 2011 May

Publication series

NameCurrent Problems in Dermatology
ISSN (Print)1421-5721
ISSN (Electronic)1662-2944

ASJC Scopus subject areas

  • Dermatology


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