Identification of the keratin K9 R162W mutation in patients of Italian origin with epidermolytic palmoplantar keratoderma

Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant skin disorder characterized by hyperkeratosis of the palms and soles associated with histologic findings of hyperkeratosis and epidermolysis. Ultrastructurally, there is vacuolization of the cytoplasm and abnormal keratin filament network with tonofilament clumping. EPPK is caused by mutations in the keratin 9 gene (KRT9), which is expressed exclusively in suprabasal keratinocytes of palmoplantar epidermis. The mutation R162W is the most frequent keratin 9 alteration reported in patients from different geographical areas. We present three unrelated Italian families affected by EPPK in which we confirmed the presence of the R162W mutation, by RT-PCR analysis followed by sequencing of the KRT9 gene, in all affected members. The finding of the same mutation in all patients, together with the previous reports of the disease, strongly suggest that position 162 of the KRT9 gene represents a mutation "hotspot", probably due to the peculiarity of the sequence.