Novel splice site mutation in keratin 1 underlies mild epidermolytic palmoplantar keratoderma in three kindreds

We report a novel mutation in the exon 6 splice donor site of keratin 1 (G4 134A) that segregates with a palmoplantar keratoderma in three kindreds, Th e nucleotide substitution leads Co the utilization of a novel in-frame spli ce site 54 bases downstream of the mutation with the subsequent insertion o f 18 amino acids into the 2B rod domain. This mutation appears to have a mi lder effect than previously described mutations in the helix initiation and termination sequence on the function of the rod domain, with regard to fil ament assembly and stability. Affected individuals displayed only mild foca l epidermolysis in the spinous layer of palmoplantar epidermis, in comparis on with cases of bullous congenital ichthyosiform erythroderma also due to keratin 1 mutations, which show widespread and severe epidermolysis. This s tudy describes a novel mutation in KRT1 that results in a phenotype distinc t from classical bullous congenital ichthyosiform erythroderma.