Loss of Corneodesmosin Leads to Severe Skin Barrier Defect, Pruritus, and Atopy

Unraveling the Peeling Skin Disease

Vinzenz Oji, Katja-Martina Eckl, Karin Aufenvenne, Marc Nätebus, Tatjana Tarinski, Katharina Ackermann, Natalia Seller, Dieter Metze, Gudrun Nürnberg, Regina Fölster-holst, Monika Schäfer-Korting, Ingrid Hausser, Heiko Traupe, Hans Christian Hennies

Research output: Contribution to journalArticle

130 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)274-81
Number of pages8
JournalAmerican Journal of Human Genetics
Volume87
Issue number2
DOIs
Publication statusPublished - 13 Aug 2010
Externally publishedYes

Fingerprint

Pruritus
Skin Diseases
Skin
Netherton Syndrome
Ichthyosis Vulgaris
Exfoliative Dermatitis
Food Hypersensitivity
Nonsense Codon
Genome
Phenotype
Mutation

Cite this

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. / Loss of Corneodesmosin Leads to Severe Skin Barrier Defect, Pruritus, and Atopy : Unraveling the Peeling Skin Disease. In: American Journal of Human Genetics. 2010 ; Vol. 87, No. 2. pp. 274-81.
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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.",
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Oji, V, Eckl, K-M, Aufenvenne, K, Nätebus, M, Tarinski, T, Ackermann, K, Seller, N, Metze, D, Nürnberg, G, Fölster-holst, R, Schäfer-Korting, M, Hausser, I, Traupe, H & Hennies, HC 2010, 'Loss of Corneodesmosin Leads to Severe Skin Barrier Defect, Pruritus, and Atopy: Unraveling the Peeling Skin Disease', American Journal of Human Genetics, vol. 87, no. 2, pp. 274-81. https://doi.org/10.1016/j.ajhg.2010.07.005

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

In: American Journal of Human Genetics, Vol. 87, No. 2, 13.08.2010, p. 274-81.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Loss of Corneodesmosin Leads to Severe Skin Barrier Defect, Pruritus, and Atopy

T2 - Unraveling the Peeling Skin Disease

AU - Oji, Vinzenz

AU - Eckl, Katja-Martina

AU - Aufenvenne, Karin

AU - Nätebus, Marc

AU - Tarinski, Tatjana

AU - Ackermann, Katharina

AU - Seller, Natalia

AU - Metze, Dieter

AU - Nürnberg, Gudrun

AU - Fölster-holst, Regina

AU - Schäfer-Korting, Monika

AU - Hausser, Ingrid

AU - Traupe, Heiko

AU - Hennies, Hans Christian

PY - 2010/8/13

Y1 - 2010/8/13

N2 - 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.

AB - 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.

KW - Base Sequence

KW - Child

KW - Chromosome Mapping

KW - DNA Mutational Analysis

KW - Epidermis

KW - Family

KW - Glycoproteins

KW - Humans

KW - Male

KW - Models, Biological

KW - Molecular Sequence Data

KW - Pedigree

KW - Pruritus

KW - Skin

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.ajhg.2010.07.005

DO - 10.1016/j.ajhg.2010.07.005

M3 - Article

VL - 87

SP - 274

EP - 281

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

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ER -