White sponge nevus is caused by mutations in mucosal keratins

Cannon's white sponge nevus is a rare, autosomal dominant disorder affecting non-cornified, stratified, squamous epithelia. Clinically, it appears as 'spongy' plaques on the oral mucosa. Recently, two distinct genetic defects on the 1A domain of keratins have been reported in one Italian and two Scottish families with white sponge nevus. The former defect is an in-frame deletion that results in the loss of an asparagine in keratin 4 (K4); while the latter family carries a single base pair mutation that leads to a leucine to proline substitution in keratin 13 (K13). Both defects result in abnormal K4/K13 heterodimer formation and irregular protofibrils. These findings extend the molecular defects described in intermediate keratin filaments, confirming the molecular role of the aggregation domains corresponding to genetic 'hot spots' for mutations. Furthermore, the identification of the molecular defects defines the correct target for new therapeutic approaches.