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A recurrent mutation in the loricrin gene underlies the ichthyotic variant of Vohwinkel syndrome
Author(s) -
O'Driscoll J.,
Muston G. C.,
McGrath J. A.,
Lam H. M.,
Ashworth J.,
Christiano A. M.
Publication year - 2002
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1046/j.1365-2230.2002.01031.x
Subject(s) - loricrin , mutation , ichthyosis , genetics , mutant , palmoplantar keratoderma , hyperkeratosis , biology , gene mutation , gene , cancer research , cellular differentiation , involucrin
Summary Vohwinkel syndrome (VS) is a family of genodermatoses which exhibits extensive clinical and genetic heterogeneity. Here, we studied a pedigree originating from the UK with typical features of the ichthyotic variant of VS and identified a recurrent insertion mutation in the loricrin gene resulting in a mutant polypeptide with an unusual C terminus. Functional studies in transgenic mice have shown that the accumulation of mutant loricrin in the nucleus appears to interfere with the later stages of epidermal differentiation, thereby explaining the clinical manifestations of ichthyosis, keratoderma and pseudoainhum. Our findings extend the body of evidence implicating mutations in the loricrin gene as the underlying cause of VS.