With the recent identification of MECP2 mutations in Rett syndrome it is quite likely that genetic factors not only play a major role in brain development but may also influence other organ growth including bone formation.
With the recent discovery that the MECP2 gene is responsible for most cases of Rett syndrome, it is possible to molecularly assess cases of affected males by direct sequencing analysis.
With the recent 50th anniversary of the first publication on Rett syndrome, and the almost 20 years since the first report on the link between Rett syndrome and MECP2 mutations, it is important to reflect on the tremendous advances in our understanding and their implications for the diagnosis and treatment of this neurodevelopmental disorder.
With the possibility of a translatable gene therapy treatment for RTT emerging, a comprehensive overview of the preclinical MECP2 gene therapy studies published thus far is warranted.
With the development of new technologies, deciphering the role of MeCP2 on a genome-wide scale is important for understanding of the RTT disease mechanisms.
While most studies addressed postsynaptic defects in the absence of MeCP2, we took advantage of an <i>in vivo</i> activity-paradigm (seizures), two models of MeCP2 deficiency, and neurobiological assays to reveal novel defects in presynaptic structural plasticity in the hippocampus in RTT rodent models.
While encouraging for prospective gene replacement treatments, it remains unclear whether additional Rett syndrome co-morbidities recapitulated in Mecp2-deficient mice will be similarly responsive to the delayed reintroduction of functional Mecp2.
We used the British Isles Rett syndrome survey to identify 137 subjects with one of the nine most frequent MECP2 gene mutations and invited their parents or carers to participate in a postal questionnaire and telephone interview.
We used a mouse model of Rett syndrome to evaluate whether residual MECP2 activity in neural stem cells (NSCs) induced the senescence phenomena that could affect stem cell function.
We treated MeCP2-null mice from postnatal-day 28 for two weeks with desipramine, already tested in RTT, or mirtazapine, an antidepressant with limited side-effects, known to promote GABA release.
We tested the hypothesis that increasing methyl-group pools might promote transcriptional repression by other methyl-binding proteins or by mutant methyl-CpG-binding protein 2 with altered affinity, ameliorating the clinical features of Rett syndrome.
We suggest that a simple PCR can easily detect deletions in the hotspot CTS region of the MECP2 gene and can be used for routine molecular diagnostics of RS.
We studied 1577 patients with RTT-like clinical diagnoses and reviewed patients who were previously studied and thought to have RTT genes by Sanger sequencing.
We show that this approach can be used to introduce PTMs and biochemical probes into a range of proteins including Cas9 nuclease and the transcriptional regulator MeCP2, which causes Rett syndrome when mutated.
We set out to identify long-range cis-regulatory sequences that differentially regulate MECP2 transcription and, when mutated, may contribute to the pathogenesis of RTT, autism or X-linked mental retardation.
We searched for mutations by sequencing the MECP2 coding region in 45 sporadic cases (35 with classic RTT, eight with variant forms and two males) and in seven families with two or more affected females.
We review recent progress in this area, focusing on two examples of mouse models of autism spectrum disorders (ASDs): Mecp2 models of Rett syndrome, and a Met-knockout model of non-syndromic forms of autism.
We report a 4-year-old boy with a Rett syndrome phenotype and his unaffected mother both carrying a 44 bp truncating deletion mutation (c.1158del44 or p.388X) in the MECP2 gene.