Genetics of PC

Pachyonychia Congenita (PC) is a genetic disorder. This means that a mutation or change in a gene causes the condition. In PC, the mutation is found in any of five keratin genes KRT6A, KRT6B, KRT6C, KRT16 or KRT17.

Keratin genes encode for keratins, which are tough, fibrous proteins that form filaments which support and give shape and strength to skin cells. A person has PC if they carry a mutation in any one of the five genes linked to PC. Mutations in any of the other 54 keratin genes are linked to other skin disorders which may be similar to PC.

More than 100 different mutations have now been identified in genes linked to PC. Those with PC present a syndrome of different features which vary based on the gene involved and the specific mutation as well as individual differences. The Mutations Chart from the PC patient registry data lists the more than 100 specific mutations now found in the five PC genes.

Keratins help cells handle pressure and stretching. In PC, mutations cause the keratin filaments to form incorrectly, creating cell fragility. This results in painful blisters and calluses, nail dystrophy, cysts, and other characteristics of PC.

PC may be hereditary (inherited from a parent who has PC) or spontaneous (a mutation occurring when no parent or other family member has PC).

PC is a dominant disorder caused by a mutation in only one copy of the gene. A recessive disorder is only caused when both copies of a gene are affected.

PC is an autosomal disorder and is not affected by gender (whether the person is male or female).

The pattern of inheritance in PC is known as autosomal dominant. Every individual has two copies of every gene. A person with PC has a mutation (change) in one copy of one of the keratin genes; the other copy is not affected. At conception, each parent gives one copy of each gene to the child. The parent with PC has a 50/50 chance of either passing the unaffected gene or passing the mutated gene. This is true for each pregnancy. If the gene with the mutation is passed on, that child will have PC. If the gene that is not affected is passed on, that child will not have PC and cannot pass PC to offspring.

The distribution of PC is not limited by or increased due to nationality or ethnicity. PC is found in every country and culture and affects males and females equally.

The following information is provided by geneticists who are members of our Medical and Scientific Advisory Board (MSAB):

PREIMPLANTATION GENETIC DIAGNOSIS (PGD)

“Pre-pregnancy Testing involves harvesting sperm and eggs, then creating embryos and testing them before implantation in the uterus. This is Preimplantation Genetic Diagnosis (or PGD, for short). There are several places in the US that perform this service, including Genesis Genetics and the Reproductive Genetics Institute (see:genesisgenetics.org and www.reproductivegenetics.com).” PGD may not be available in all countries. Current techniques may only be available to those with inherited PC who have other living affected family members so that multiple samples are available. A physician can refer to a genetic counselor who can assist in referral for PGD if available.”

PRENATAL TESTING

“Prenatal testing is performed after conception (during pregnancy and before birth). The testing is conducted on the fetus. Again, this would be organized by a genetic counselor.”

UNIVERSITY OF UTAH GENETIC SCIENCE LEARNING CENTER

There are some great interactive graphics and videos to explain genetics and inheritance on the learn genetics website. The Pachyonychia Congenita page on this site also has good genetic information but still lists the old categories for Pachyonychia Congenita.