Rett Syndrome

Abstract

Rett syndrome is a neurological disease of early postnatal brain growth found almost exclusively in girls and is the third most common cause, after Down syndrome and Fragile X syndrome, of severe mental retardation. Typically, girls with Rett syndrome show developmental regression including loss of communication and motor skills, stereotypic hand movements and a deceleration of head growth. The defective gene, methyl CpG binding protein 2 (Rett syndrome) (MECP2) is normally involved in the transcription silencing of genes (turning genes ‘off ’). In Rett syndrome, the MECP2 protein does not work properly in approximately half of the patient's cells due to X inactivation. This is thought to lead to inappropriate communication between MECP2‐positive and MECP2‐negative cells in the brain, and the Rett syndrome phenotype.

Keywords: Rett syndrome; RTT; neurological disorder; MECP2; X‐inactivation; CDKL2

Figure 1.

Role of MECP2 in transcription silencing and Rett syndrome. Representative diagram of MECP2‐mediated silencing of genes (top panel). MECP2 binds methylcytosines (CmG) and recruits transcriptional repressor Sin3a and histone deacetylase HDAC1 and HDAC2 to the MECP2–DNA complex. HDAC1 and HDAC2 remove acetyl moieties from histones. Deacetylated histones, which are more negatively charged, cause the chromatin to become more compacted, leading to the silencing of genes. As shown by the lower diagram, MECP2 does not function properly in Rett syndrome, leading to the expression of genes normally regulated by MECP2.

Figure 2.

Schematic diagrams of the MECP2 gene and common mutations in Rett syndrome. The MECP2 gene consists of four exons (E1–E4), three introns and a large (>8.5 kb) 3′ untranslated region (3′‐UTR). The two highly conserved regions of the gene are the methyl‐binding domain (MBD) and the transcriptional repression domain (TRD).

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Web Links

GeneReviews: www.Genetests.org, enter in Rett syndrome

Methyl CpG binding protein 2 (Rett syndrome) (MECP2); Locus ID: 4204. LocusLink: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=4204

Methyl CpG binding protein 2 (Rett syndrome) (MECP2); MIM number: 312750. OMIM: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=312750

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How to Cite close
Bradbury, Margaret K, Hoffbuhr, Kristen C, and Hoffman, Eric P(Sep 2007) Rett Syndrome. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005687.pub2]