Clearly, some individuals with MECP2 Duplications are more severely affected than others and we really don’t know why. We do know a few things:
A. Some individuals with duplications seem to face much more severe challenges than others.
B. The length of the duplication seems to have little to do with severity.
C. Triplication of the MECP2 gene typically produces more severe effects than duplication.
D. Siblings or cousins in the same genetic line seem to have similar levels of severity.
One reason for the differences in severity could be that other genes help regulate the amount of MECP2 Protein or the activity of MECP2 Protein. For example, one or more other genes might influence the rate of breakdown or excretion of MECP2 protein and more active versions of these genes could help offset overproduction.
Another idea, however, is that there are differing types of the MECP2 gene that are more or less active. Duplications might produce more severe symptoms for individuals with a more active variant than those with a less active variant.
In fact, we know that there are variations in the structure of MECP2 genes. At least 1326 SNPs have been reported so far. SNPs (Single-Neucleotide Polymorphisms) are variations in one of the many bases that make up DNA. So not every MECP2 Gene is exactly the same. It is sort of like spelling differences. One person might spell her name V-I-C-K-Y and another person might spell her name V-I-C-K-I but either way, it is pronounced the same. However, if we change the V to an R or an M, the name is pronounced differently. In one case, we would be likely to say that two people have the same name but spell it differently. In the second case, we would be more likely to say they had different names. So, some small variations in spelling can make a big difference and some don’t seem to make any difference at all. The same is true with variations in genes.
Research on Rett syndrome has already shown us that different variations in the MECP2 Gene have differing effects. Some variations produce more severe forms than others.
It is possible that other variations in the MECP2 gene may influence the level of activity of the gene in all of us and also influence the severity among individuals with duplications.
My knowledge of genetics is pretty minimal. So if anyone who reads this has some thoughts on this idea, it would be great to get some comments.