Rett%20Syndrome

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Rett Syndrome

• By Thu Le

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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

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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.

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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.

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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)

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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
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Truncation at R168X (Phenylalanine 56)
(300005.0020),
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Truncation
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References

• http//www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id
  312750
• http//www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd
  SearchdbbooksdoptcmdlGenBookHLtermRettSyndr
  omeANDgnd5Bbook5DAND1380745Buid5Dridgnd.
  section.216
• http//www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd
  SearchdbbooksdoptcmdlGenBookHLtermRettSyndr
  omeANDgene5Bbook5DAND4136375Buid5Dridgen
  e.chapter.rettrett.T1
• http//www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd
  SearchdbbooksdoptcmdlGenBookHLtermRettSyndr
  omeANDgene5Bbook5DAND4136375Buid5Dridgen
  e.chapter.rettrett.Nomenclature
• http//www.rcsb.org/pdb/explore.do?structureId1QK
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