What are the genetic changes related to erythrokeratodermia variabilis et progressiva ?
EKVP can be caused by mutations in the GJB3 or GJB4 gene. These genes provide instructions for making proteins called connexin 31 and connexin 30.3, respectively. These proteins are part of the connexin family, a group of proteins that form channels called gap junctions on the surface of cells. Gap junctions open and close to regulate the flow of nutrients, charged atoms (ions), and other signaling molecules from one cell to another. They are essential for direct communication between neighboring cells. Gap junctions formed with connexin 31 and connexin 30.3 are found in several tissues, including the outermost layer of skin (the epidermis).  The GJB3 and GJB4 gene mutations that cause EKVP alter the structure of the connexins produced from these genes. Studies suggest that the abnormal proteins can build up in a cell structure called the endoplasmic reticulum (ER), triggering a harmful process known as ER stress. Researchers suspect that ER stress damages and leads to the premature death of cells in the epidermis. This cell death leads to skin inflammation, which appears to underlie the development of erythematous areas. The mechanism by which epidermal damage and cell death contributes to hyperkeratosis is poorly understood.  In some cases, affected individuals have no identified mutation in the GJB3 or GJB4 gene. In these individuals, the cause of the disorder is unknown. Researchers suspect that changes in other, unidentified genes may also be associated with EKVP.