Rett syndrome affects brain development, typically causing severe dyspraxia (severe motor impairment). Severity varies widely. Some affected girls and women, given a suitable means of communication, display normal intelligence. Others may develop intellectual disabilities. Seizures are common. About 50% are unable to walk. The syndrome is seen mostly in females, because for male fetuses it is often lethal before birth.
90% of cases appear to be caused by mutations in methyl CpG binding protein 2 (MeCP2), a gene in the X chromosome. In at least 95% of Rett syndrome cases, the cause is a de novo mutation in the child. That is, it is not inherited from either parent. The parents' MeCP2 genes are normal. Rett syndrome patients are fertile but unlikely to have children. Therefore the mutations are rapidly lost from the human gene pool.
More than 60 mutations have been identified that cause Rett syndrome. 65% are single nucleotide point mutations C ==> T. Three common ones occur in the domain that binds methylated DNA: R106W, R133C, and T158M.
PDB code: 3c2i.
by Eric Martz, University of Massachusetts, 2012
Thanks to Kim Johnson (R255X) and Jill Johnson (Australia), and to Susan Irby (New Jersey, USA) for their advice which made this page more accurate and appropriate.
Dragich, J. et al.: Rett syndrome: a surprising result of mutation in MECP2. Hum. Mol. Genet. (2000) 9(16): 2365-2375 doi:10.1093/hmg/9.16.2365.