title: On the role of the epidermal differentiation complex in ichthyosis vulgaris, atopic dermatitis and psoriasis.
abstract: Undisturbed epidermal differentiation is crucial for an intact skin barrier function. The epidermal differentiation complex (EDC) is a cluster of genes on chromosome 1q21 encoding proteins that fulfil important functions in terminal differentiation in the human epidermis, including filaggrin, loricrin, S100 proteins and others. Recently, evidence emerged that variation within EDC genes plays an important role in the pathogenesis of three common skin disorders, ichthyosis vulgaris, atopic dermatitis (AD) and psoriasis. Two loss-of-function mutations in the filaggrin (FLG) gene, R501X and 2282del4, were identified as causative for ichthyosis vulgaris in 15 affected European families, and the mode of inheritance was found to be semidominant. As ichthyosis vulgaris and AD often occur concomitantly in affected individuals, these two mutations were subsequently investigated in AD patients and found to be strongly associated with the disease. Following this first report, seven replication studies have been performed that all confirm an association of these two mutations with AD (or AD subtypes) in several European cohorts. Additionally, two unique loss-of-function mutations in the FLG gene were identified in Japanese ichthyosis vulgaris families and found to be associated with AD in a Japanese cohort. Thus, the FLG mutations are among the most consistently replicated associations for AD. Additionally, linkage analysis has suggested that variation within the EDC might also predispose for psoriasis but the exact susceptibility variation(s) have not yet been elucidated. Taken together, these findings convincingly demonstrate the important role of barrier dysfunction in various common skin disorders.
authors.affiliation: Department of Human Genetics, Ruhr-University, Universitätsstrasse 150, 44801 Bochum, Germany. sabine.hoffjan@rub.de
authors.forename: S
authors.initials: S
authors.lastname: Hoffjan
authors.forename: S
authors.initials: S
authors.lastname: Stemmler
mesh_terms: D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D003876:Dermatitis, Atopic / Q000235:genetics*; D005260:Female; D000091344:Filaggrin Proteins; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D016112:Ichthyosis Vulgaris / Q000235:genetics*; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011565:Psoriasis / Q000235:genetics*
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins