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Identification of the first nonsense CDSN mutation with expression of a truncated protein causing peeling skin
A Mallet1, M Kypriotou, K George
1UMR 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, 31059, Toulouse CEDEX 9, France.
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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