Rett Syndrome: On Clinical and Genetic Features, and Experimental Models Based on MeCP2 Dysfunction.

CALFA G, PERCY AK, POZZO-MILLER L

The Autism: Molecules to model systems

Oxford University Press

Año: 2013; p. 57 - 90

Rett syndrome (RTT ; Online MendelianInheritance in Man #312750; htt p://www.ncbi.nlm.nih.gov/omim/), fi rst recognized anddescribed in German by Andreas Rett (Rett ,1966), is a neurodevelopmental disorder predominantlyoccurring in females. Almost 20years later, Hagberg and colleagues presentedthe fi rst description of RTT in the English language,leading to worldwide diagnosis in all ethnicand racial groups (Hagberg, Aicardi, Dias, &Ramos, 1983). Currently, the incidence of RTT isestimated to be approximately 1:10, 000 femalebirths (Chahrour & Zoghbi, 2007; Laurvicket al., 2006). Early studies proposing a geneticbasis for RTT were later confi rmed by Zoghbiand colleagues with the identifi cation of mutationsin the MECP2 gene located at chromosomeXq28 (Amir et al., 1999). MECP2 encodesmethyl-CpG-binding protein2, a transcriptionfactor that binds methylated DNA and is ubiquitouslyexpressed in mammalian tissues (Lewiset al., 1992). Following the identifi cation of lossof-function mutations in the MECP2 gene inindividuals with RTT , research eff orts expandedrapidly on an international scale with comprehensiveclinical investigations into the complexarray of medical and behavioral issues. Inaddition, intensive laboratory-based studieshave been spurred by the availability of humanautopsy tissue and experimental animal models,such as deletions of the endogenous Mecp2gene (knockout), insertions of premature STOPcodons or RTT -associated mutations (knock-in)common in the human MECP2 gene, and overexpressionof MECP2 to model the newly identifiedMECP2 duplication syndrome (Friez et al.,2006; Meins et al., 2005; Ramocki, Tavyev, &Peters, 2010).