title: A recurrent mutation in the loricrin gene underlies the ichthyotic variant of Vohwinkel syndrome.
abstract: 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.
authors.affiliation: Stepping Hill Hospital, Stockport NHS Trust, UK.
authors.forename: J
authors.initials: J
authors.lastname: O'Driscoll
authors.forename: G C
authors.initials: GC
authors.lastname: Muston
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
authors.forename: H M
authors.initials: HM
authors.lastname: Lam
authors.forename: J
authors.initials: J
authors.lastname: Ashworth
authors.forename: A M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D005260:Female; D006801:Humans; D007057:Ichthyosis / Q000235:genetics* / Q000473:pathology; D007645:Keratoderma, Palmoplantar / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D010375:Pedigree; D010641:Phenotype; D013577:Syndrome
chemical_list: D008565:Membrane Proteins; C064554:loricrin