MECP2

The MECP2 gene provides instructions for making a protein (MeCP2) that is essential for normal brain development. This protein seems to be important for the function of nerve cells in the brain and is present in high levels in mature nerve cells.

Studies suggest that the MeCP2 protein plays a role in forming connections (synapses) between nerve cells, where cell-to-cell communication occurs. This protein turns off (silences) several other genes, preventing them from making proteins when they are not needed. It remains uncertain which genes are targeted by the MeCP2 protein, but such genes are probably important for normal brain function, particularly the formation of synapses.

Researchers believe that the MeCP2 protein is also involved in processing molecules called messenger RNA (mRNA), which serve as genetic blueprints for making proteins. By cutting and rearranging mRNA molecules in different ways, the MeCP2 protein controls the production of different versions of certain proteins. This process is known as alternative splicing. In the brain, the alternative splicing of many proteins is critical for normal communication between nerve cells.

Rett syndrome - caused by mutations in the MECP2 gene

More than 200 mutations in the MECP2 gene have been identified in females with Rett syndrome. These mutations include changes in single DNA building blocks (base pairs), insertions or deletions of DNA in the gene, and changes that affect how the gene is processed into a protein. MECP2 mutations alter the structure of the MeCP2 protein or reduce the amount of protein that is produced. As a result, cells do not have enough MeCP2 protein to bind to DNA and silence other genes. Genes that are normally regulated by this protein remain active and continue to make proteins when they are not needed. Mutations in the MECP2 gene may also disrupt alternative splicing of proteins critical for communication between nerve cells. Although these defects disrupt normal brain development, it remains unclear how MECP2 mutations lead to the signs and symptoms of Rett syndrome.

MECP2 mutations also have been identified in some males with features similar to classic Rett syndrome. These mutations often occur after conception and are present in only a fraction of the body's cells. In a few cases, researchers have discovered that the MECP2 gene is abnormally duplicated in boys with intellectual disability and some developmental problems characteristic of Rett syndrome.

other disorders - associated with the MECP2 gene

Mutations in the MECP2 gene have also been identified in people with several other disorders that affect the brain. For example, MECP2 mutations are associated with some cases of moderate to severe X-linked mental retardation (XLMR). Mutations in the MECP2 gene have also been found in males with severe brain dysfunction (neonatal encephalopathy) who live only into early childhood. In addition, several people with the features of Rett syndrome and signs and symptoms similar to Angelman syndrome (a condition characterized by intellectual disability, problems with movement, and inappropriate laughter and excitability) have mutations in the MECP2 gene. MECP2 mutations or changes in the gene's activity have been reported in some cases of autism, which is a developmental disorder that affects communication and social interaction. Lastly, duplications of the MECP2 gene have been associated with a progressive, life-threatening brain disorder that causes severe intellectual disability, weak muscle tone (hypotonia), and seizures.