In 1999, NICHD-supported scientists discovered that most girls with Rett syndrome have a change in the pattern of a single gene— the Methyl-CpG-binding Protein 2 (MECP2) gene on the X chromosome. Between 90% and 95% of girls with Rett syndrome have a mutation in this gene.
This gene makes methyl-CpG-binding protein 2 (MeCP2), which is necessary for the development of the nervous system—especially the brain. The mutation causes the gene to make less than the needed amounts of the protein, or to make a damaged protein that the body can't use. As a result, there may not be enough usable amount of the protein for the brain to develop normally.
Researchers are still trying to understand exactly how the brain uses MeCP2 and how problems with the protein cause the typical features of Rett syndrome. Normally, MeCP2 helps to turn off certain genes that make different proteins in nerve cells and other cells. Without MeCP2, the body keeps making these materials, even when it no longer needs them. After a while, having high amounts of these materials in the body may actually start to hurt the nervous system and cause the problems of Rett syndrome.
But, not all people with Rett syndrome have a genetic mutation. In 5 percent of people with Rett syndrome, an MECP2 mutation is not present or is not detectable. And, some people who have mutations on the MECP2 gene don't show the typical features of Rett syndrome. Researchers are looking at different genes to see if they, too, can cause the symptoms of Rett syndrome.
