Rett Syndrome
By Thu Le
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
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.
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.
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)
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
Truncation at R168X
(Phenylalanine 56) (300005.0020),
Truncation
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
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.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.Nomenclature
• http://www.rcsb.org/pdb/explore.do?structureId=1QK9