There are two major aspects of the disease that are important to really understand it. The first is the genetics of PMD and the second relates to the effect of PLP mutations on the nervous system. First I’ll describe the genetics.
PMD occurs due to genetic mutation. In the tens of thousands of gene pairs, sometimes one will be changed. The mutation may be inherited or may happen by itself. Sometimes a mutated gene will not cause problems. Other times, a gene with a mutation will cause the body not to work correctly, and that person will have a genetic condition such as PMD. Genes are carried on chromosomes and most individuals have 46 chromosomes in each cell in their body. The chromosomes come in 23 pairs with the first 22 pairs being identical in males and in females. The last pair is the sex chromosomes; females have two X chromosomes, while males have one X and one Y chromosome. The chromosome can be thought of like a bookcase and the gene as a book located on the bookcase. DNA (deoxyribonucleic acid – see Figure 1), which is the basic component of the gene, is like the letters in the book. Genetic information is stored, and passed down from generation to generation, in the form of the precise sequence of DNA letters or bases.
Since the gene for PMD is located on the X chromosome, the disease typically affects only boys or men in a family. Technically, this is called X linked inheritance. Remember that females have two X chromosomes while males have one X and one Y chromosome. If there is a gene on the X chromosome that is not working properly, males will be affected more often than females. Females likely have a gene on the other X chromosome that does work properly and compensates for the defective X chromosome. Females who carry the gene for PMD therefore typically are not affected since the PLP gene on the other X chromosome is normal. Males with PMD are usually not able to have children. So, when it occurs in several generations, women act as the carriers for the PMD mutation and pass on the disease. Women who carry the PMD gene have a 50% or 1 in 2 chance of passing it on to their sons and their daughters. These odds are the same for every pregnancy. What happened in one pregnancy does not in any way influence the odds for the next pregnancy. Sons who inherit the gene would be affected, whereas daughters would be carriers. If a daughter did not inherit the PMD gene, then she would not pass PMD on to her children.