title: Loss of corneodesmosin leads to severe skin barrier defect, pruritus, and atopy: unraveling the peeling skin disease.
abstract: Generalized peeling skin disease is an autosomal-recessive ichthyosiform erythroderma characterized by lifelong patchy peeling of the skin. After genome-wide linkage analysis, we have identified a homozygous nonsense mutation in CDSN in a large consanguineous family with generalized peeling skin, pruritus, and food allergies, which leads to a complete loss of corneodesmosin. In contrast to hypotrichosis simplex, which can be associated with specific dominant CDSN mutations, peeling skin disease is characterized by a complete loss of CDSN expression. The skin phenotype is consistent with a recent murine Cdsn knockout model. Using three-dimensional human skin models, we demonstrate that lack of corneodesmosin causes an epidermal barrier defect supposed to account for the predisposition to atopic diseases, and we confirm the role of corneodesmosin as a decisive epidermal adhesion molecule. Therefore, peeling skin disease will represent a new model disorder for atopic diseases, similarly to Netherton syndrome and ichthyosis vulgaris in the recent past.
authors.affiliation: Department of Dermatology, University Hospital Münster, 48149 Münster, Germany.
authors.forename: Vinzenz
authors.initials: V
authors.lastname: Oji
authors.forename: Katja-Martina
authors.initials: KM
authors.lastname: Eckl
authors.forename: Karin
authors.initials: K
authors.lastname: Aufenvenne
authors.forename: Marc
authors.initials: M
authors.lastname: Nätebus
authors.forename: Tatjana
authors.initials: T
authors.lastname: Tarinski
authors.forename: Katharina
authors.initials: K
authors.lastname: Ackermann
authors.forename: Natalia
authors.initials: N
authors.lastname: Seller
authors.forename: Dieter
authors.initials: D
authors.lastname: Metze
authors.forename: Gudrun
authors.initials: G
authors.lastname: Nürnberg
authors.forename: Regina
authors.initials: R
authors.lastname: Fölster-Holst
authors.forename: Monika
authors.initials: M
authors.lastname: Schäfer-Korting
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hausser
authors.forename: Heiko
authors.initials: H
authors.lastname: Traupe
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Hennies
mesh_terms: D001483:Base Sequence; D002648:Child; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D004817:Epidermis / Q000473:pathology; D005190:Family; D006023:Glycoproteins / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D010375:Pedigree; D011537:Pruritus / Q000150:complications* / Q000235:genetics*; D012867:Skin / Q000473:pathology / Q000648:ultrastructure
chemical_list: C109656:CDSN protein, human; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins