The DUX4gene has an essential function in human life. Unfortunately, none of us can remember the prime days of the DUX4gene. That is because we are talking here about the very early stage of the formation of the human embryo. When the task of the gene is completed, it is permanently disabled in mature human cells. There are some minor exceptions (like germ cells), but we can generally assume that this gene is inactive. At least it should be.
The problem begins when the mechanisms that secure our genetic code (DNA) fail. Mutations in a particular area of our DNA may cause the DUX4gene reactivation in mature cells. We can think about it in terms of a regulation issued by the superior. Its content was prepared on festive paper - this is our DNA. Unfortunately, the message contains a typo (mutation), as a result of which the command changes from "please DO NOT activate DUX4" to "please activate DUX4".
You may ask yourself, so many problems from just one typo? Unfortunately, this typo was made in a unique, significant place, changing the content of the genetic regulation so much that it caused a particular problem. On top of everything else, our DNA is like a hundred-volume epic. No wonder that employees (specific cells of tissues) of a large corporation (our whole body) look only at the fragment of interest. As a result, the corporate machine continues to run like nothing happened. So, there is no ill will here, employees are just very thorough here, and unfortunately, they follow the wrong regulation to the letter.
Hence, the DNA fragment (the DUX4gene) is read (activated), which leads to the production of the DUX4 protein. Unfortunately, the body's mature cells (more specifically, the muscles) cannot bear the unannounced visitor. The newcomer thinks that he has been guided to the right place, from which he does not intend to leave. This leads to a stalemate, and the toxic atmosphere only builds up, making the muscle cells function worse and worse.
Depending on the causative mutation and, consequently, the various processes leading to the activation of the DUX4gene, we distinguish FSHD type 1 (FSHD1) and FSHD type 2 (FSHD2). Type 1 FSHD accounts for 95% of cases, and the mutation occurs in the region adjacent to the DUX4gene (the so-called D4Z4 repeat sequence). Type 2 FSHD accounts for the remaining 5% of mutations occurring elsewhere in the genetic code but with a similar result. Clinically, both types are the same.
DUX4