Palmoplantar keratoderma caused by a missense variant in CTSB encoding cathepsin B.
Clin Exp Dermatol
; 46(1): 103-108, 2021 Jan.
Article
em En
| MEDLINE
| ID: mdl-32683719
ABSTRACT
BACKGROUND:
Palmoplantar keratoderma (PPK) refers to a large group of disorders characterized by extensive genetic and phenotypic heterogeneity. PPK diagnosis therefore increasingly relies upon genetic analysis.AIM:
To delineate the genetic defect underlying a case of diffuse erythematous PPK associated with peeling of the skin.METHODS:
Whole exome and direct sequencing, real-time quantitative PCR, protein modelling and a cathepsin B enzymatic assay were used.RESULTS:
The patient studied had severe diffuse erythematous PPK transgrediens. Pedigree analysis suggested an autosomal dominant mode of inheritance. Whole exome sequencing revealed a heterozygous missense mutation in the CTSB gene, encoding the cysteine protease cathepsin B. Genomic duplications in a noncoding region, which regulates the expression of CTSB, were recently found to cause erythrokeratolysis hiemalis, a rare autosomal dominant disorder of cornification. This mutation affects a highly conserved residue, and is predicted to be pathogenic. Protein modelling indicated that the mutation is likely to lead to increased endopeptidase cathepsin B activity. Accordingly, the CTSB variant was found to result in increased cathepsin B proteolytic activity.CONCLUSION:
In summary, we report the identification of the first gain-of-function missense mutation in CTSB, which was found to be associated in one individual with a dominant form of diffuse PPK.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Catepsina B
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Ceratodermia Palmar e Plantar
/
Mutação de Sentido Incorreto
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Clin Exp Dermatol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Israel