Rett syndrome (RTT) is a devastating genetic disorder that worldwide represents the most common genetic cause of severe intellectual disability in females. Most cases are caused by mutations in the X-linked MECP2 gene. Several recent studies have demonstrated that RTT mimicking animal models do not develop an irreversible condition and phenotypic rescue is possible. However, no cure for RTT has been identified so far, and patients are only given symptomatic and supportive treatments. The development of clinical applications imposes a more comprehensive knowledge of MeCP2 functional role(s) and their relevance for RTT pathobiology. Herein, we thoroughly survey the knowledge about MeCP2 structure and functions, highlighting the necessity of identifying more functional domains and the value of molecular genetics. Given that, in our opinion, RTT ultimately is generated by perturbations in gene transcription and so far no genes/pathways have been consistently linked to a dysfunctional MeCP2, we have used higher-level bioinformatic analyses to identify commonly deregulated mechanisms in MeCP2-defective samples. In this review we present our results and discuss the possible value of the utilized approach.
Rett syndrome and the urge of novel approaches to study MeCP2 functions and mechanisms of action / F. Bedogni, R.L. Rossi, F. Galli, C. Cobolli Gigli, A. Gandaglia, C. Kilstrup-Nielsen, N. Landsberger. - In: NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS. - ISSN 0149-7634. - 46:2(2014 Oct), pp. 187-201. [10.1016/j.neubiorev.2014.01.011]
Rett syndrome and the urge of novel approaches to study MeCP2 functions and mechanisms of action
N. LandsbergerUltimo
2014
Abstract
Rett syndrome (RTT) is a devastating genetic disorder that worldwide represents the most common genetic cause of severe intellectual disability in females. Most cases are caused by mutations in the X-linked MECP2 gene. Several recent studies have demonstrated that RTT mimicking animal models do not develop an irreversible condition and phenotypic rescue is possible. However, no cure for RTT has been identified so far, and patients are only given symptomatic and supportive treatments. The development of clinical applications imposes a more comprehensive knowledge of MeCP2 functional role(s) and their relevance for RTT pathobiology. Herein, we thoroughly survey the knowledge about MeCP2 structure and functions, highlighting the necessity of identifying more functional domains and the value of molecular genetics. Given that, in our opinion, RTT ultimately is generated by perturbations in gene transcription and so far no genes/pathways have been consistently linked to a dysfunctional MeCP2, we have used higher-level bioinformatic analyses to identify commonly deregulated mechanisms in MeCP2-defective samples. In this review we present our results and discuss the possible value of the utilized approach.File | Dimensione | Formato | |
---|---|---|---|
Bedogni et al. 2014.pdf
accesso riservato
Tipologia:
Publisher's version/PDF
Dimensione
2.05 MB
Formato
Adobe PDF
|
2.05 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.