What are the genetic changes related to epidermolytic hyperkeratosis ?
Mutations in the KRT1 or KRT10 genes are responsible for epidermolytic hyperkeratosis. These genes provide instructions for making proteins called keratin 1 and keratin 10, which are found in cells called keratinocytes in the outer layer of the skin (the epidermis). The tough, fibrous keratin proteins attach to each other and form fibers called intermediate filaments, which form networks and provide strength and resiliency to the epidermis.  Mutations in the KRT1 or KRT10 genes lead to changes in the keratin proteins, preventing them from forming strong, stable intermediate filament networks within cells. Without a strong network, keratinocytes become fragile and are easily damaged, which can lead to blistering in response to friction or mild trauma. It is unclear how these mutations cause the overgrowth of epidermal cells that results in hyperkeratotic skin.  KRT1 gene mutations are associated with PS-type epidermal hyperkeratosis, and KRT10 gene mutations are usually associated with NPS-type. The keratin 1 protein is present in the keratinocytes of the skin on the palms of the hands and the soles of the feet as well as other parts of the body, so mutations in the KRT1 gene lead to skin problems in these areas. The keratin 10 protein is not found in the skin of the palms and soles, so these areas are unaffected by mutations in the KRT10 gene.