{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:34:42Z","timestamp":1790696082403,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2002,5,30]],"date-time":"2002-05-30T00:00:00Z","timestamp":1022716800000},"content-version":"vor","delay-in-days":149,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ment. Retard. Dev. Disabil. Res. Rev."],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rett syndrome is a neurodevelopmental disorder of early postnatal brain growth in girls. Patients show a normal neonatal period with subsequent developmental regression and a loss of acquired skills (communication and motor skills), deceleration of head growth, and development of typical hand stereotypies. Recent studies have shown that mutations in the X\u2010linked methyl CpG binding protein 2 gene (<jats:italic>MeCP2<\/jats:italic>) cause most typical cases of Rett syndrome. The <jats:italic>MeCP2<\/jats:italic> gene encodes a protein that binds methylated cytosine residues of CpG dinucleotides and mediates, with histone deacetylases and transcriptional repressors, the transcription \u201csilencing\u201d of other genes. Girls with Rett syndrome exhibit mosaic expression for the MeCP2 defect at the cellular level, with most patients showing random X\u2010inactivation and approximately equal numbers of cells expressing the normal <jats:italic>MeCP2<\/jats:italic> gene and the mutated <jats:italic>MeCP2<\/jats:italic> gene. In rare cases, females with a <jats:italic>MeCP2<\/jats:italic> mutation escape phenotypic expression of the disorder because of nonrandom X\u2010inactivation and the preferential inactivation of the mutated <jats:italic>MeCP2<\/jats:italic> allele. Nonrandom patterns of X\u2010inactivation may also contribute to the clinical variability often seen in girls with Rett syndrome. The spectrum of clinical phenotype caused by <jats:italic>MeCP2<\/jats:italic> mutations is wide, including milder \u201cpreserved speech\u201d variants, the severe congenital Rett variant, and a subset of X\u2010linked recessive mental retardation in boys. Studies have shown that atypical and classical Rett syndrome can caused by the same <jats:italic>MeCP2<\/jats:italic> mutations, indicating clinical phenotype is variable even among girls with the same <jats:italic>MeCP2<\/jats:italic> mutation. The relationship between type of <jats:italic>MeCP2<\/jats:italic> mutation, X\u2010inactivation status, and clinical phenotype of Rett syndrome is complex and likely involves other environmental and polygenic modifiers. 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