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.
Identification of the first nonsense CDSN mutation with expression of a truncated protein causing peeling skin syndrome type B
Article first published online: 2 DEC 2013
© 2013 British Association of Dermatologists
British Journal of Dermatology
Volume 169, Issue 6, pages 1322–1325, December 2013
How to Cite
Mallet, A., Kypriotou, M., George, K., Leclerc, E., Rivero, D., Mazereeuw-Hautier, J., Serre, G., Huber, M., Jonca, N. and Hohl, D. (2013), Identification of the first nonsense CDSN mutation with expression of a truncated protein causing peeling skin syndrome type B. British Journal of Dermatology, 169: 1322–1325. doi: 10.1111/bjd.12593
Conflicts of interest None declared.
A.M. and M.K. contributed equally to this study.
- Issue published online: 2 DEC 2013
- Article first published online: 2 DEC 2013
- Accepted manuscript online: 19 AUG 2013 10:27AM EST
- Manuscript Accepted: 13 AUG 2013
- Biomedical Research Federative Structure of Toulouse
Peeling skin disease (PSD), a generalized inflammatory form of peeling skin syndrome, is caused by autosomal recessive nonsense mutations in the corneodesmosin gene (CDSN).
To investigate a novel mutation in CDSN.
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.
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.
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.