PC-K17

ABOUT THE KRT17 GENE

The KRT17 gene provides instructions for making a protein called keratin 17 or K17. Keratins are a group of tough, fibrous proteins that form the structural framework of certain cells, particularly cells that make up the skin, hair, nails, and similar tissues. Keratin 17 is produced in the nails, the hair follicles, and the skin on the palms of the hands and soles of the feet. It is also found in the skin’s sebaceous glands, which produce an oily substance called sebum.

Keratin 17 partners with a similar protein, keratin 6b, to form molecules called keratin intermediate filaments. These filaments assemble into dense networks that provide strength and resiliency to the skin, nails, and other tissues. Networks of keratin filaments protect these tissues from being damaged by friction and other everyday physical stresses. Keratin 17 is also among several keratins involved in wound healing.

The KRT17 mutations responsible for pachyonychia congenita change the structure of keratin 17, preventing it from working effectively with keratin 6b and interfering with the assembly of the keratin intermediate filament network. Without this network, skin cells become fragile and are easily damaged, making the skin less resistant to friction and minor trauma. Even normal activities such as walking can cause skin cells to break down, resulting in the formation of painful blisters and calluses. In the sebaceous glands, abnormal keratin filaments lead to the development of cysts called steatocystomas.

Defective keratin 17 also disrupts the growth and function of cells in the nails and hair follicles, which explains why the signs and symptoms of pachyonychia congenita also affect these tissues. (Adapted from http://ghr.nlm.nih.gov/gene/KRT17.)

To learn how many others have mutations in the same gene and the same mutation, visit the PC data page where there is detailed information on those with PC and the various mutations.

Observations on PC-K17 from the IPCRR

Those with PC-K17 have the greatest variation of phenotypes for PC.

• The condition may be evident at birth due to natal teeth. This type of PC often has natal teeth (but not all with PC-K17 have natal teeth).
  
• Some nail dystrophy may also be present at birth but the nail changes may be milder than those with other types of PC.
  
• Nearly 50% of PC-K17 patients have little or no plantar keratoderma and pain.
  
• More than 50% of PC-K17 patients have extensive plantar keratoderma and pain.
  
• Pain levels for PC-K17 patients may range from 1 to 9 on a 0 to 10 scale.
  
• Leukokeratosis in oral mucosa is rarely present in PC-K17.
  
• Extensive steatocystoma cysts (steatocystoma multiplex or SM) is found in almost all PC-K17 patients. However, not all those with SM have mutations in the KRT17 gene

IPCRR Data for PC-K17