Modelling RTT in vitro by knocking down the expression of the MeCP2 protein with shRNA, we found that choline supplementation to MeCP2-knockdown neurons increased their soma sizes and the complexity of their dendritic arbors.
Typical RTT is caused by de novo mutations of the gene MECP2 (OMIM*300005), and atypical forms of RTT can be caused by mutations of the CDKL5 (OMIM*300203) and FOXG1 (OMIM*164874) genes.
The reclassification of variants (such as VUS) in MECP2 gene associated with RETT syndrome suggest that the combinatory in-silico predictor approach had a higher success rate in categorizing their pathogenicity.
Loss-of-function mutations affecting MeCP2 are the primary cause of Rett syndrome (RTT), a severe neurological disorder that is thought to result from absence of functional protein in the brain.
Rett Syndrome (RTT) is a neurological disorder mainly associated with mutations in the X-linked gene coding for the methyl-CpG binding protein 2 (MECP2).
The X-linked gene MECP2, associated to several neurodevelopmental disorders such as Rett syndrome, encodes the protein methyl-CpG-binding protein 2 (MeCP2), a regulatory protein that has been implicated in neuronal maturation and refinement of olfactory circuits.
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations or deletions in Methyl-CpG-binding Protein 2 (MeCP2), a brain-enriched transcriptional regulator.
Here, I review the evidence linking MeCP2 deficiency to alterations in neurotransmission and neural circuits that govern the psychomotor function and discuss a recently identified pathological origin underlying the psychomotor deficits in RTT.
Herein, we dissect the role of impaired MECP2 function in triggering senescence along with other senescence-related aspects, such as metabolism, in MSCs from a mouse model of RTT.
In this chapter, we will briefly review the functions of the MeCP2 protein and how its mutations are implicated in Rett syndrome and other neuropsychiatric disorders.
In summary, we provide a new strategy for MECP2 gene targeting that can be potentially translated into gene therapy or for iPSCs-based disease modeling of RTT syndrome.
Our findings, as well as literature findings, suggest that early brain abnormalities associated with RTT/RTT-l (with MECP2 mutations) can be detected as regionally decreased cerebellar volumes.
By demonstrating that different MECP2 mutations can produce concordant neurological phenotypes but discordant molecular features, we highlight the importance of considering personalized approaches for the treatment of Rett syndrome.
Rett syndrome (RTT), a neurodevelopmental disorder, is mainly caused by mutations in methyl CpG-binding protein 2 (<i>MECP2</i>), which has multiple functions such as binding to methylated DNA or interacting with a transcriptional co-repressor complex.
The questionnaire was completed by 271 parents whose daughters met the clinical criteria for RTT and/or had MECP2 mutations and participated in the Natural History of Rett Syndrome Study.
Mutations in the MECP2 gene are the main cause of Rett syndrome (RTT), a pervasive neurodevelopmental disorder, that shows also multisystem disturbances associated with a metabolic component.
Despite being a monogenic disorder, the pathogenic mechanisms by which mutations in MeCP2 impair neuronal function and underlie the RTT symptoms have been challenging to elucidate.
Research aimed at the underlying pathophysiological mechanisms of RTT and MDS has significantly advanced our understanding of MeCP2 functions in the nervous system.