Facts about MeCP2, the Rett Syndrome Gene
Rett Syndrome is caused, in large part, by a mutation in a gene located on the X chromosome. This Rett syndrome gene, known as MeCP2, and its location on the female chromosome, explain why the disorder primarily strikes girls. Rett Syndrome first came to public light in the 1960s thanks to Dr. Andreas Rett. The MeCP2 gene mutation discovery came in 1999.
Discovery of the MeCP2 Gene
Researchers at Baylor University in Palo Alto, California discovered the connection between mutations in the MeCP2 gene and Rett syndrome in 1999. Specifically, Ruthie Amir, a fellow at the university, discovered the gene and that if mutated, symptoms of Rett syndrome presented.
MeCP2 (pronounced meck-pee-too) is the acronym for methyl CpG binding protein 2. This particular Rett syndrome gene is found on the X chromosome at the 28th position, a cytogenetic location listed as Xq28. That places the gene on the long arm of the X chromosome.
As the main Rett syndrome gene, MeCP2 provides the instructions for making a protein that is important in normal brain development. It is believed to be involved in the formation of synapses where communication between nerve cells takes place. The MeCP2 protein also turns off other genes, preventing them from making proteins that are not needed.
MeCP2 Mutations and Rett Syndrome
Scientists studying the MeCP2 gene in Rett syndrome patients have identified more than 200 different mutations, including changes in single base pairs and insertions and deletions of chunks of the genetic material. The mutations either alter the shape of the MeCP2 protein or reduce the amount that is produced. The result of this is that there is not enough of the normal functioning protein to stick to other genes and turn them off (silence them).
Boys and MeCP2
Boys with mutations in the MeCP2 gene seldom survive past birth. For the few who do, mutations of the gene do not appear in all body cells. In fact, only a small percentage of cells have any mutation in the MeCP2 gene, resulting in intellectual disabilities, but not Rett syndrome.
Other Disorders Linked to MeCP2
In addition to identifying MeCP2 as the main Rett syndrome gene, various research projects have identified mutations in the MeCP2 gene in patients with other disorders such as Angelman syndrome, X-linked intellectual disability (XLMR,) and autism. In fact, Dr. Huda Zoghbi, head of the research team at Baylor responsible for discovering the MeCP2 gene, received a Genius Grant to further study connections between MeCP2 and autism.
References and Resources
Autism Speaks https://www.autismspeaks.org/science/science_news/genius_award_gene_retts.php
Genetics Home Reference https://ghr.nlm.nih.gov/gene/MECP2
Rett Syndrome Research Trust https://www.rsrt.org/about-Rett/what-causes-Rett-Syndrome.html