A recurrent mutation in the loricrin gene underlies the ichthyotic variant of Vohwinkel syndrome


A. M. Christiano, Departments of Dermatology and Genetics & Development, Columbia University, College of Physicians & Surgeons, 630 West 168th Street VC-1526, New York, NY 10032, USA. Tel.: +1 212 305 9565. Fax: +1 212 305 7391. E-mail: amc65@columbia.edu


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.