title: Towards characterization of palmoplantar keratoderma caused by gain-of-function mutation in loricrin: analysis of a family and review of the literature.
abstract: Loricrin keratoderma is an autosomal dominant palmoplantar keratoderma heterogeneous in clinical appearance. We report a family with diffuse ichthyosis and honeycomb palmoplantar keratoderma but no occurrence of pseudoainhums or autoamputations. All patients were born as collodion babies and displayed prominent knuckle pads. We identified the previously reported mutation 730insG in LOR, which elongates loricrin by 22 amino acids because of delayed termination. As pseudoainhums are missing in all patients of the family reported, we propose two compulsory features of loricrin keratoderma: (i) honeycomb palmoplantar keratoderma and (ii) diffuse ichthyosiform dermatosis. Therefore we suggest that the condition should be described clinically as 'honeycomb palmoplantar keratoderma with ichthyosis'. Furthermore, we have assessed the amounts of transcript of LOR using pyrosequencing. This revealed an equal expression of mutant and wild-type alleles of LOR in an affected individual. These findings further underline the gain-of-function theory for mutant LOR in loricrin keratoderma.
authors.affiliation: Division of Dermatogenetics, Cologne Centre for Genomics, University of Cologne, Zülpicher Str. 47, 50674 Cologne, Germany.
authors.forename: M M
authors.initials: MM
authors.lastname: Gedicke
authors.forename: H
authors.initials: H
authors.lastname: Traupe
authors.forename: B
authors.initials: B
authors.lastname: Fischer
authors.forename: S
authors.initials: S
authors.lastname: Tinschert
authors.forename: H C
authors.initials: HC
authors.lastname: Hennies
mesh_terms: D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000235:genetics* / Q000473:pathology; D007645:Keratoderma, Palmoplantar / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012873:Skin Diseases, Genetic / Q000235:genetics* / Q000473:pathology
chemical_list: D008565:Membrane Proteins; C064554:loricrin