PC-K6c

ABOUT THE KRT6C GENE

The KRT6C gene provides instructions for making a protein called keratin 6c or K6c. 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 6c is found in the skin, although it is unknown which other tissues may produce this protein.

Keratin 6c is a component of molecules called keratin intermediate filaments. These filaments assemble into dense networks that provide strength and resilience to the skin, nails, and other tissues. Networks of keratin filaments protect these tissues from being damaged by friction and other everyday physical stresses.

The KRT6C mutations responsible for PC-K6c change the structure of keratin 6c and interfere with the assembly of the keratin intermediate filament network. Skin cells with defective keratin are fragile and prone to damage, making the skin less resistant to friction and minor trauma. The soles of the feet experience a significant amount of friction compared with many other parts of the body and must bear the body’s weight, which may help explain why blisters and calluses occur primarily in this area in people with focal palmoplantar keratoderma. (Adapted from http://ghr.nlm.nih.gov/gene/KRT6C.)

Publications

M. E. Schwartz et al. Pachyonychia Congenita Project: A Partnership of Patient and Medical Professional. Journal of the Dermatology Nurses’ Association. 2013;5(1):42-47.

W. H. McLean et al. The
phenotypic and molecular genetic features of pachyonychia congenita. J Invest Dermatol. 2011;131(5):1015-7.

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-K6c from the IPCRR

Patients with mutations in PC-K6c may be considered the mildest form of PC in that they do not have many of the secondary features of PC. (See data charts below.) However, like all types of PC, patients with K6c mutations may experience painful calluses on the bottoms of the feet that can be debilitating and limiting. Also, because we have information on so few patients with PC-K6c, it is not possible to generalize findings.

In 2010, Professor Bowden outlined the challenge that existed regarding whether changes in KRT6C should be classified as Pachyonychia Congenita. “Twenty years have elapsed since keratin mutations were linked to cutaneous genodermatoses, and we now know that they cause 40 different genetic disorders. (Researchers) have identified KRT6C mutations in patients with focal palmoplantar keratoderma (FPPK), but debate concerning overlapping phenotypes between FPPK and pachyonychia congenita (PC) will continue because only one family has nail involvement. Furthermore, screening of control DNA samples identified 3 in 335 individuals (1%) who had a mutation (K6c p.Asn172del), but the phenotype was not ascertained”, Mutations in a keratin 6 isomer (K6c) cause a type of focal palmoplantar keratoderma. Journal of Investigative Dermatology 130 (2) , pp. 336-338. 10.1038/jid.2009.395.

NOTE:  Now that there are additional cases in the International PC Research Registry (IPCRR), mutations in KRT6C have been accepted as PC-K6c. Publications since 2011, by those active in the International PC Consortium (IPCC), consistently include KRT6C mutations as one of the types of PC.

IPCRR Data for PC-K6c