Ichthyosis Genetics - 6
Where do Dominant Genes Start?
If a disorder like epidermolytic ichthyosis (EI) is fully dominant and always shows up if the gene is present, where did that first instance come from? How can it happen that the disorder appears in a family that had no previous history of it?
That first case in a family probably came about from a spontaneous mutation of a gene. In this age of movies and television, we tend to think of a mutation as something very dramatic, and usually negative. A mutation, however, is simply any new genetic change. Mutations can arise from a multitude of causes, some known, some as yet unknown. Although it may sound like a contradiction in terms, mutations are natural events. In fact, they are the very basis of evolution. Genes mutate at random: some of the changes are bad - they produce a defect or disorder which makes life more difficult for the organism; or they can be good - making the organism stronger and more efficient in its environment. If Mr. and Mrs. Normal Skin have a child with epidermolytic ichthyosis (EI), the disorder was probably caused by a spontaneous mutation in one of the genes causing this condition.
What's important for the person with epidermolytic ichthyosis (EI) to remember is that the causative gene is dominant. It doesn't matter where it came from - inherited from a parent who has epidermolytic ichthyosis (EI) or arising as a result of a spontaneous mutation- once it occurs, it persists and behaves like any other dominant gene. It will dominate the gene for normal skin in any subsequent generation. A dominant gene, just because it appeared spontaneously, will not disappear spontaneously. Anyone who has epidermolytic ichthyosis (EI) has a dominant gene for that disorder and a 50-50 chance, with each pregnancy, of passing it on to his/her child.
It is important to recognize that the preceding discussion has been simplified. Furthermore, there is often a certain amount of variability within each disorder. For instance, it is very slightly possible for a person to inherit a dominant disorder yet fail to express it at all. He would, nonetheless, pass it on as the dominant gene that it is, and his offspring could display it in full force, thus giving the appearance of "skipped generations." This phenomenon, called non-penetrance, is not common, and is more likely to occur in some dominant disorders than in others.
In other instances, two people within one family inherit a disorder, but one gets a mild case and the other gets a severe case, though both have the same disorder, caused by the same genetic mutation. This phenomenon is termed variable expressivity and, again, it is more likely to occur in some genetic disorders than others. This can be the case, for example in some pachyonchia congenita families.
 Mutations can also be neutral and have no apparent effect on the organism’s survival. These mutations, termed genetic polymorphisms, are very common in the genome and are passed on through families, fanning out into the general population. Genetic polymorphisms, therefore, are useful markers of relatedness.
The information presented here is designed to be generally informative and is derived from sources believed reliable. The genetic concepts involved are extremely technical in many cases and have been simplified for clarity. The information presented is not, nor is it intended to be, sufficient for readers to make any decision about their personal genetic situations. Readers should always consult a professional geneticist or physician for individualized genetic counseling before making any decisions in their individual cases.
This information is provided as a service to patients and parents of patients who have ichthyosis. It is not intended to supplement appropriate medical care, but instead to complement that care with guidance in practical issues facing patients and parents. Neither FIRST, its Board of Directors, Medical & Scientific Advisory Board, Board of Medical Editors, nor Foundation staff and officials endorse any treatments or products reported here. All issues pertaining to the care of patients with ichthyosis should be discussed with a dermatologist experienced in the treatment of their skin disorder.