Identification of the first nonsense CDSN mutation with expression of a truncated protein causing peeling skin syndrome type B.
Détails
ID Serval
serval:BIB_985948B77F35
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Identification of the first nonsense CDSN mutation with expression of a truncated protein causing peeling skin syndrome type B.
Périodique
British Journal of Dermatology
ISSN
1365-2133 (Electronic)
ISSN-L
0007-0963
Statut éditorial
Publié
Date de publication
2013
Volume
169
Numéro
6
Pages
1322-1325
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish. pdf type: Concise Communication.
Résumé
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.
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.
Pubmed
Web of science
Création de la notice
16/01/2014 19:02
Dernière modification de la notice
20/08/2019 15:00