Identification of the first nonsense CDSN mutation with expression of a truncated protein causing peeling skin syndrome type B

Authors

  • A. Mallet,

    1. UMR 5165/U1056 ‘Unité de Différenciation Epidermique et Autoimmunité Rhumatoïde’ (CNRS, INSERM Université Toulouse III CHU de Toulouse), Hôpital Purpan, Place du Dr Baylac, TSA 40031, Toulouse CEDEX 9, France
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  • M. Kypriotou,

    1. Laboratory of Cutaneous Biology, Service of Dermatology and Venereology, Beaumont Hospital CHUV, Lausanne, Switzerland
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  • K. George,

    1. Laboratory of Cutaneous Biology, Service of Dermatology and Venereology, Beaumont Hospital CHUV, Lausanne, Switzerland
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  • E. Leclerc,

    1. UMR 5165/U1056 ‘Unité de Différenciation Epidermique et Autoimmunité Rhumatoïde’ (CNRS, INSERM Université Toulouse III CHU de Toulouse), Hôpital Purpan, Place du Dr Baylac, TSA 40031, Toulouse CEDEX 9, France
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  • D. Rivero,

    1. Laboratory of Cutaneous Biology, Service of Dermatology and Venereology, Beaumont Hospital CHUV, Lausanne, Switzerland
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  • J. Mazereeuw-Hautier,

    1. UMR 5165/U1056 ‘Unité de Différenciation Epidermique et Autoimmunité Rhumatoïde’ (CNRS, INSERM Université Toulouse III CHU de Toulouse), Hôpital Purpan, Place du Dr Baylac, TSA 40031, Toulouse CEDEX 9, France
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  • G. Serre,

    1. UMR 5165/U1056 ‘Unité de Différenciation Epidermique et Autoimmunité Rhumatoïde’ (CNRS, INSERM Université Toulouse III CHU de Toulouse), Hôpital Purpan, Place du Dr Baylac, TSA 40031, Toulouse CEDEX 9, France
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  • M. Huber,

    1. Laboratory of Cutaneous Biology, Service of Dermatology and Venereology, Beaumont Hospital CHUV, Lausanne, Switzerland
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  • N. Jonca,

    1. UMR 5165/U1056 ‘Unité de Différenciation Epidermique et Autoimmunité Rhumatoïde’ (CNRS, INSERM Université Toulouse III CHU de Toulouse), Hôpital Purpan, Place du Dr Baylac, TSA 40031, Toulouse CEDEX 9, France
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  • D. Hohl

    Corresponding author
    1. Laboratory of Cutaneous Biology, Service of Dermatology and Venereology, Beaumont Hospital CHUV, Lausanne, Switzerland
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  • Funding sources This work was supported by grants from the Swiss National Science Foundation to D.H., from the Bangerter Foundation to M.K. and D.H., and from the Fondation pour la Recherche Médicale to A.M.
  • Conflicts of interest None declared.
  • A.M. and M.K. contributed equally to this study.

Summary

Background

Peeling skin disease (PSD), a generalized inflammatory form of peeling skin syndrome, is caused by autosomal recessive nonsense mutations in the corneodesmosin gene (CDSN).

Objectives

To investigate a novel mutation in CDSN.

Methods

A 50-year-old white woman showed widespread peeling with erythema and elevated serum IgE. DNA sequencing, immunohistochemistry, Western blot and real-time polymerase chain reaction analyses of skin biopsies were performed in order to study the genetics and to characterize the molecular profile of the disease.

Results

Histology showed hyperkeratosis and acanthosis of the epidermis, and inflammatory infiltrates in the dermis. DNA sequencing revealed a homozygous mutation leading to a premature termination codon in CDSN: p.Gly142*. Protein analyses showed reduced expression of a 16-kDa corneodesmosin mutant in the upper epidermal layers, whereas the full-length protein was absent.

Conclusions

These results are interesting regarding the genotype–phenotype correlations in diseases caused by CDSN mutations. The PSD-causing CDSN mutations identified heretofore result in total corneodesmosin loss, suggesting that PSD is due to full corneodesmosin deficiency. Here, we show for the first time that a mutant corneodesmosin can be stably expressed in some patients with PSD, and that this truncated protein is very probably nonfunctional.

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