• MECP2 gene
• mental retardation
• molecular genetics
• Rett syndrome

• CTD, C-terminal domain
• MBD, methyl binding domain
• NLS, nuclear localisation signal
• RTT, Rett syndrome
• RSDCWG, Rett Syndrome Diagnostic Criteria Work Group
• TRD, transcription repression domain

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that almost exclusively affects females and is generally considered lethal in males during gestation. The typical form is characterised, at anamnesis, by an initial period of stagnation of development followed by regression lasting for several months and occurring between 6 months and 3 years of age. The fully developed clinical picture is dominated by mental retardation, reduction of communication skills, and loss of purposeful hand movements combined with hand stereotypes, progressive microcephaly, abnormal locomotion, and other various minor signs.¹ The prevalence of RTT has been estimated to be between 0.25 and 1 per 10 000 in girls; the figure is probably higher if variant forms are included.² In 1999, it was discovered that a significant proportion of RTT cases are caused by mutations in the MECP2 gene.³ However, detection of mutations has been very variable from one series to another, ranging from 19%³ to 100% positive cases,⁴ presumably due to the profile of the populations studied.

Methyl CpG-binding protein 2 is encoded by a gene containing four exons. Its longest transcript is 10.1 kb and is mainly expressed in the fetal brain. This 446 residue protein acts as a transcriptional repressor. It includes a methyl binding domain (MBD, residues 78–162), a transcription repression domain (TRD, residues 207–310), a nuclear localisation signal (NLS, residues 255–271), and a 63 residue C-terminal domain (CTD) involved in binding to DNA and in protein stability (reviewed by Nomura et al⁵).

A number of variant phenotypes in girls was described before the molecular era and included: a form with congenital onset,^5,6 a form with early infantile onset dominated by seizures,⁷ a form fruste,⁸ a form with late childhood regression,⁹ and a form with preservation of speech. …