Children with Rett Syndrome (RTT) appear to develop normally until 6 to 18 months of age, when they enter a period of regression, losing speech and motor skills. Most develop repetitive hand movements, irregular breathing patterns, seizures and motor control problems. RTT leaves its victims profoundly disabled, requiring maximum assistance with every aspect of daily living.
Mutations in a gene called MECP2 (methyl CpG-binding protein 2) were identified in 1999 as the leading cause of RTT. MECP2 is believed to function as a transcriptional repressor of its downstream genes. When genes need to be silenced so that a protein is not produced in a given cell, methyl groups attach to CpG dinucleotides, which are often clustered in areas of the gene called CpG islands. MECP2 then binds to these methylated CpG sites, shutting down the gene's production of its protein.
Faulty over-expression of target genes caused by mutated MeCP2 is an underlying hypothesis explaining RTT symptoms. Although MeCP2 is expressed throughout the body, RTT is a disorder of the central nervous system and therefore it is crucial to identify MECP2's target genes in the brain.
Dr. Kohwi-Shigematsu and colleagues have identified an MECP2 target gene, DLX5, involved in the synthesis of GABA, gamma-aminobutyric acid, an important neurotransmitter. Interestingly, DLX5 is an imprinted gene, meaning its expression status depends on whether the gene came from the mother or the f
Contact: Monica Coenraads
Rett Syndrome Research Foundation