Loss of Corneodesmosin Leads to Severe Skin Barrier Defect, Pruritus, and Atopy: Unraveling the Peeling Skin Disease

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, pr...

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Bibliographic Details
Published in:American journal of human genetics 2010-08, Vol.87 (2), p.274-281
Main Authors: Oji, Vinzenz, Eckl, Katja-Martina, Aufenvenne, Karin, Nätebus, Marc, Tarinski, Tatjana, Ackermann, Katharina, Seller, Natalia, Metze, Dieter, Nürnberg, Gudrun, Fölster-Holst, Regina, Schäfer-Korting, Monika, Hausser, Ingrid, Traupe, Heiko, Hennies, Hans Christian
Format: Article
Language:English
Subjects:
Base Sequence
Biological and medical sciences
Child
Chromosome Mapping
Dermatology
DNA Mutational Analysis
Epidermis - pathology
Family
Fundamental and applied biological sciences. Psychology
General aspects. Genetic counseling
Genes
Genetics of eukaryotes. Biological and molecular evolution
Genomics
Genotype & phenotype
Glycoproteins - deficiency
Glycoproteins - genetics
Hereditary diseases of the skin. Congenital diseases of the skin. Haemangioma of the skin, of mucosae and of soft tissue
Humans
Male
Medical genetics
Medical sciences
Models, Biological
Molecular and cellular biology
Molecular Sequence Data
Mutation
Pedigree
Pruritus - complications
Pruritus - genetics
Skin - pathology
Skin - ultrastructure
Skin diseases
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Description
Summary: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.
ISSN:0002-9297
1537-6605
DOI:10.1016/j.ajhg.2010.07.005