In 1999, NICHD-supported scientists1 discovered that most girls with Rett syndrome had a change in the pattern of a single gene—the Methylcytosine-binding protein 2 (MECP2) gene on the X chromosome. Research shows that between 90% and 95% of girls with Rett syndrome have a mutation in this gene.2,3 This gene makes Methylcytosine-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 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 products, even when it no longer needs them. After a while, having high amounts of these products in the body may actually start to damage the nervous system and cause the problems of Rett syndrome.
In 2002, scientists funded by the NICHD developed a new mouse model for Rett syndrome. This mouse model more closely mimicked the symptoms of Rett syndrome found in humans than did earlier mouse models. For more on the development of this mouse model, visit the NICHD news release at: http://www.nichd.nih.gov/news/releases/pages/rett_syndrome.aspx
Until 2008, researchers did not know the extent to which MECP2 controlled multiple functions in the brain. That is when NICHD-supported researchers discovered the gene's numerous roles not only as a repressor but also as an activator of thousands of other genes in order to maintain proper brain functions. For more on this research, see NIH Researchers Find That Rett Syndrome Gene is Full of Surprises.
Much of the NICHD's research on Rett syndrome is supported through its Intellectual and Developmental Disabilities Branch (IDDB). The NICHD has provided grants for research in the following areas:
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