These family members as well as their target genes are now additional candidate genes that, when mutated, may cause similar disruptions to normal brain development and functioning. Moreover, as was discussed above, several enzymatic steps are required before genes can be repressed. It is likely that mutations in some of these genes will have an effect on gene expression through inappropriate regulation of transcription. Six different types of mutations were found in the 7 children who had mutations present in their MeCP2 gene. Two of these children were half-sisters and carried the same mutation.
Several mutations are missense mutations that substitute one amino acid for another.
These missense mutations are found in the methyl-binding domain and are thought to disrupt its ability to recognize and interact with methyl groups. The remaining mutations are found within the second functional region, the domain that recruits the deacetylation complex. Mutations in this domain also result in disruption of transcriptional repression. One of these mutations is caused by the insertion of a single nucleotide that leads to a shift in the downstream nucleotide sequence. This results in a completely different amino acid sequence in the portion of the protein beyond the mutation.