A novel H1 mutation in the keratin 1 chain in epidermolytic hyperkeratosis.

We report a novel mutation in a case of epidermolytic hyperkeratosis that results in a proline for arginine substitution in the penultimate residue position of the H1 subdomain of the keratin 1 chain, which is near the beginning of the rod domain. This causes a severe clinical disease classified as PS-2. Therefore, the H1 subdomain is probably equally important for the maintenance of keratin intermediate filament integrity as the rod domain. Since earlier concepts had implied that mutations in the H1 subdomain produce milder disease, this case suggests that attempts to correlate mutations with disease presentation remain problematic.