1. Rett Syndrome By Thu Le

2. What is Rett Syndrome? Progressive neurodevelopment disorder Common cause of profound mental impairment in girls Babies with Rett syndrome develops normally until the age of 6 to 18 months until their development regresses They lose the purposeful use of their hands and are disabled for life with reduced muscle tone and seizures and lose of communication skills

4. Rett syndrome is caused by…… Mutations in the gene Methyl CpG binding protein 2 (MeCP2) found on the X chromosome MeCP2 is called a "transcriptional repressor" because it codes for a protein that controls the expression of other genes. MeCP2 gene provides instruction for making the MeCp2 protein that is essential for normal brain development Depending on what part of the gene contains the mutation, partial loss of this protein changes the environment experienced by developmentally important proteins which, in turn, leads to the RTT phenotype.

5. Allelic Variants mutations in the MECP2 gene in both classic and Preserved Speech Variant (PSV) Rett syndrome establishing that the 2 forms are allelic disorders Difference between PSV and classic Rett syndrome: PSV patients typically recover some degree of speech and hand use and usually do not show growth failure. Progressive scoliosis, epilepsy, and other minor handicaps, usually present in Rett syndrome, are rare in the preserved speech variant.

6. Mutations in MeCP2 Conserved domain MECP2 mutations found in RTT patients have been late truncating mutations 4 early truncating hotspot mutations, R168X (300005.0020), R255X (300005.0021), R270X (300005.0005), and R294X (300005.0011)300005.0020300005.0021300005.0005300005.0011

7. MeCP2 Mutations in the gene alter the structure of the MeCP2 protein or lead to reduced amounts of the protein As a result, the protein is unable to bind to DNA or turn off other genes. Genes that are normally regulated by MeCP2 remain active and continue to make large amounts of particular proteins when they are not needed. This defect disrupts the normal functioning of nerve cells, leading to the signs and symptoms of Rett syndrome

9. Truncation at R168X (Phenylalanine 56) (300005.0020),300005.0020

10. Truncation

11. References http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=312750 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db =books&doptcmdl=GenBookHL&term=Rett+Syndrome+AND+g nd%5Bbook%5D+AND+138074%5Buid%5D&rid=gnd.section.21 6http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db =books&doptcmdl=GenBookHL&term=Rett+Syndrome+AND+g nd%5Bbook%5D+AND+138074%5Buid%5D&rid=gnd.section.21 6 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db =books&doptcmdl=GenBookHL&term=Rett+Syndrome+AND+g ene%5Bbook%5D+AND+413637%5Buid%5D&rid=gene.chapter. rett#rett.T1http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db =books&doptcmdl=GenBookHL&term=Rett+Syndrome+AND+g ene%5Bbook%5D+AND+413637%5Buid%5D&rid=gene.chapter. rett#rett.T1 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db =books&doptcmdl=GenBookHL&term=Rett+Syndrome+AND+g ene%5Bbook%5D+AND+413637%5Buid%5D&rid=gene.chapter. rett#rett.Nomenclaturehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db =books&doptcmdl=GenBookHL&term=Rett+Syndrome+AND+g ene%5Bbook%5D+AND+413637%5Buid%5D&rid=gene.chapter. rett#rett.Nomenclature http://www.rcsb.org/pdb/explore.do?structureId=1QK9