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This work resulted in the narrowing of the region likely to harbor the mutated gene to Xq27.3\u2010Xqter. After systematic exclusion of several candidate genes, we discovered mutations in <jats:italic>MECP2<\/jats:italic>, the gene that encodes the transcriptional repressor, methyl\u2010CpG\u2010binding protein 2. Since then, nonsense, missense, or frameshift mutations have been found in at least 80% of girls affected with classic Rett syndrome. Sixty\u2010four percent of mutations are recurrent C &gt; T transitions at eight CpG dinucleotides mutation hotspots, while the C\u2010terminal region of the gene is prone to recurrent multinucleotide deletions (11%). Most mutations are predicted to result in total or partial loss of function of MeCP2. There is no clear correlation between the type and position of the mutation and the phenotypic features of classic and variant Rett syndrome patients, and XCI appears to be a major determinant of phenotypic severity. Further research focuses on the pathogenic consequences of these mutations along the hypothesis of loss of transcriptional repression of a small number of genes that are essential for neuronal function in the maturing brain. MRDD Research Reviews 2002;8:82\u201386. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mrdd.10025","type":"journal-article","created":{"date-parts":[[2002,10,6]],"date-time":"2002-10-06T12:27:22Z","timestamp":1033907242000},"page":"82-86","source":"Crossref","is-referenced-by-count":40,"title":["Genetic basis of rett syndrome"],"prefix":"10.1002","volume":"8","author":[{"given":"Ignatia B.","family":"Van den Veyver","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huda 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