About MeCP2 & Rett Syndrome
Mutations in MeCP2 can cause Rett SyndromeMeCP2 is a DNA binding protein that has specificity for methyl-CpG. The MECP2 gene is located on the X chromosome. Mutations in MeCP2 can result in Rett Syndrome (RTT) which occurs almost exclusively in girls. Why Rett Syndrome mostly affects girlsFemales have two X chromosomes, while males have one X and one Y chromosome. In girls suffering from Rett Syndrome, one of their X chromosomes, usually that inherited from their father, contains a nonfunctional MeCP2 gene. Random X chromosome inactivation means that while half of their cells happen to have inactivated the mutant chromosome, half have inactivated the chromosome bearing the only functional copy of MeCP2 that they have. So they are effectively a mixture of cells containing 100% levels of MeCP2 activity and cells containing no functional MeCP2 at all. We suspect that most of these mutations in MECP2 result in a non-functional protein. Many missense mutations which occur within the Methyl CpG binding domain (MBD) are known to interfere with the structure of the domain. |
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The role of MeCP2 in cellsMeCP2 is a DNA binding protein. It binds specifically to methylated DNA through its Methyl-CpG Binding Domain (MBD), and can associate with histone modifying proteins through its Transcription Repression Domain (TRD) to bring about transcriptional repression. We know that MeCP2 associates with methylated DNA throughout the genome, but it is as yet not clear which genes are specifically repressed by MeCP2. Disease SymptomsRTT patients tend to develop as normal for the first 6-18 months of life, but then begin to lose the ability to speak or use their hands. This regression continues into autistic behaviour, ataxia, repetitive hand movements, and microcephaly, and often involves breathing abnormalities, seizures, eating problems, and growth retardation. RTT is a relatively common disorder, occurring once every 10,000-15000 live female births. |