CALFA GASTON DIEGO
Capítulos de libros
Título:
Rett Syndrome: On Clinical and Genetic Features, and Experimental Models Based on MeCP2 Dysfunction.
Autor/es:
CALFA G, PERCY AK, POZZO-MILLER L; POWEL CM, MONTEGGIA L
Libro:
The Autism: Molecules to model systems
Editorial:
Oxford University Press
Referencias:
Año: 2013; p. 57 - 90
Resumen:
Rett syndrome (RTT ; Online Mendelian
Inheritance in Man #312750; htt p://www.
ncbi.nlm.nih.gov/omim/), fi rst recognized and
described in German by Andreas Rett (Rett ,
1966), is a neurodevelopmental disorder predominantly
occurring in females. Almost 20
years later, Hagberg and colleagues presented
the fi rst description of RTT in the English language,
leading to worldwide diagnosis in all ethnic
and racial groups (Hagberg, Aicardi, Dias, &
Ramos, 1983). Currently, the incidence of RTT is
estimated to be approximately 1:10, 000 female
births (Chahrour & Zoghbi, 2007; Laurvick
et al., 2006). Early studies proposing a genetic
basis for RTT were later confi rmed by Zoghbi
and colleagues with the identifi cation of mutations
in the MECP2 gene located at chromosome
Xq28 (Amir et al., 1999). MECP2 encodes
methyl-CpG-binding protein2, a transcription
factor that binds methylated DNA and is ubiquitously
expressed in mammalian tissues (Lewis
et al., 1992). Following the identifi cation of lossof-
function mutations in the MECP2 gene in
individuals with RTT , research eff orts expanded
rapidly on an international scale with comprehensive
clinical investigations into the complex
array of medical and behavioral issues. In
addition, intensive laboratory-based studies
have been spurred by the availability of human
autopsy tissue and experimental animal models,
such as deletions of the endogenous Mecp2
gene (knockout), insertions of premature STOP
codons or RTT -associated mutations (knock-in)
common in the human MECP2 gene, and overexpression
of MECP2 to model the newly identified
MECP2 duplication syndrome (Friez et al.,
2006; Meins et al., 2005; Ramocki, Tavyev, &
Peters, 2010).
Inheritance in Man #312750; htt p://www.
ncbi.nlm.nih.gov/omim/), fi rst recognized and
described in German by Andreas Rett (Rett ,
1966), is a neurodevelopmental disorder predominantly
occurring in females. Almost 20
years later, Hagberg and colleagues presented
the fi rst description of RTT in the English language,
leading to worldwide diagnosis in all ethnic
and racial groups (Hagberg, Aicardi, Dias, &
Ramos, 1983). Currently, the incidence of RTT is
estimated to be approximately 1:10, 000 female
births (Chahrour & Zoghbi, 2007; Laurvick
et al., 2006). Early studies proposing a genetic
basis for RTT were later confi rmed by Zoghbi
and colleagues with the identifi cation of mutations
in the MECP2 gene located at chromosome
Xq28 (Amir et al., 1999). MECP2 encodes
methyl-CpG-binding protein2, a transcription
factor that binds methylated DNA and is ubiquitously
expressed in mammalian tissues (Lewis
et al., 1992). Following the identifi cation of lossof-
function mutations in the MECP2 gene in
individuals with RTT , research eff orts expanded
rapidly on an international scale with comprehensive
clinical investigations into the complex
array of medical and behavioral issues. In
addition, intensive laboratory-based studies
have been spurred by the availability of human
autopsy tissue and experimental animal models,
such as deletions of the endogenous Mecp2
gene (knockout), insertions of premature STOP
codons or RTT -associated mutations (knock-in)
common in the human MECP2 gene, and overexpression
of MECP2 to model the newly identified
MECP2 duplication syndrome (Friez et al.,
2006; Meins et al., 2005; Ramocki, Tavyev, &
Peters, 2010).
