KRT14

The KRT14 gene provides instructions for making a protein called keratin 14. Keratins are a group of tough, fibrous proteins that form the structural framework of certain cells, particularly cells that make up the skin, hair, and nails. Keratin 14 is specifically produced in cells called keratinocytes in the outer layer of the skin (the epidermis).

Keratin 14 partners with a similar protein, keratin 5, to form molecules called keratin intermediate filaments. These filaments assemble into strong networks that help attach keratinocytes together and anchor the epidermis to underlying layers of skin. The network of keratin intermediate filaments provides strength and resiliency to the skin and protects it from being damaged by friction and other everyday physical stresses.

Researchers believe that keratin 14 may also play a role in the formation of sweat glands and the development of patterned ridges on the skin of the hands and feet. These ridges, called dermatoglyphs, are the basis for each person's unique fingerprints.

epidermolysis bullosa simplex - caused by mutations in the KRT14 gene

More than 60 mutations in the KRT14 gene have been identified in people with epidermolysis bullosa simplex. Most of these genetic changes alter single protein building blocks (amino acids) used to make keratin 14. The most severe form of epidermolysis bullosa simplex, the Dowling-Meara type, usually results from mutations in regions of the KRT14 gene that are essential for the normal assembly of keratin intermediate filaments. Milder forms of the disorder, including the Weber-Cockayne and Koebner types, are often caused by mutations in less critical regions.

KRT14 mutations change the structure and function of keratin 14, preventing it from working effectively with keratin 5 and interfering with the assembly of the keratin intermediate filament network. A disruption in this network makes keratinocytes fragile and prone to rupture. Minor trauma to the skin, such as rubbing or scratching, can cause these cells to break down, resulting in the formation of painful, fluid-filled blisters.

other disorders - caused by mutations in the KRT14 gene

Mutations in the KRT14 gene are also responsible for two rare disorders of skin development, Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis. These related conditions are characterized by an absence of dermatoglyphs; a net-like (reticulate) pattern of dark skin coloring; thick, calloused skin on the hands and feet (palmoplantar keratoderma); and a reduced ability to sweat (hypohidrosis). Because the two conditions have such similar features and are caused by mutations in the same gene, researchers believe that they may represent a single disorder.

The KRT14 mutations associated with these conditions lead to the production of an extremely small, nonfunctional version of keratin 14. Without this protein, keratin intermediate filaments are unable to assemble into a strong, stable network. Studies suggest that KRT14 mutations may also increase the frequency of controlled cell death (apoptosis) in certain areas of the skin. These changes likely underlie the skin abnormalities characteristic of Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis.