The molecular pathology of progressive symmetric erythrokeratoderma: a frameshift mutation in the loricrin gene and perturbations in the cornified cell envelope

Abstract

The erythrokeratodermas (EKs) are a group of disorders characterized by erythematous plaques associated with variable features that include palmoplantar keratoderma. One type of EK is known as "progressive symmetric erythrokeratoderma" (PSEK). We studied members of a family of Japanese origin in which the index case with PSEK had had well-demarcated nonmigratory erythematous plaques on her extremities since birth. Sequence determination of the loricrin gene revealed an insertion of a C following nucleotide 709. The mutation results in a frameshift that changes the terminal 91 amino acids in the wild-type polypeptide into missense amino acids and adds 65 additional residues. This further implicates loricrin defects in the pathogenesis of disorders with palmoplantar keratoderma and pseudoainhum.