We recruited 110 patients who fulfilled the diagnostic criteria for Rett syndrome and were referred to Cardiff for molecular analysis, but in whom an MECP2 mutation was not identifiable.
We propose that different interactions of MeCP2 with methyl cytosines, DNA and likely other heterochromatin proteins are required for MeCP2 function and their dysfunction lead to Rett syndrome.
We previously described an isoform-specific MeCP2-e1-deficient male mouse model of a human RTT mutation that lacksMeCP2-e1 while preserving expression of MeCP2-e2.
We present evidence that MeCP2 represses gene expression by binding to methylated CA sites within long genes, and that in neurons lacking MeCP2, decreasing the expression of long genes attenuates RTT-associated cellular deficits.
We investigated the consequences of MeCP2 dysfunction on dendritic spine structure by overexpressing ( approximately twofold) MeCP2-GFP constructs encoding either the wildtype (WT) protein, or missense mutations commonly found in RTT individuals.
We identified mutations in the MECP2 gene and documented the clinical manifestations in 65 Rett syndrome patients to characterize the genotype-phenotype spectrum.
We hypothesized that early-life seizures overactivate these channels, in turn dysregulating Ca<sup>2+</sup>-dependent signaling pathways including that of methyl CPG binding protein 2 (MeCP2), a transcription factor implicated in the autism spectrum disorder (ASD) Rett Syndrome.
We have screened the CDKL5 gene in 94 patients with RTT or a RTT-like phenotype who had tested negative forMECP2 mutations (13 classical RTT female subjects, 25 atypical RTT female subjects, 40 RTT-like female and 16 RTT-like male subjects; 33 of the patients had early onset seizures).
We have screened the MECP2 gene coding region for mutations in five familial cases of Rett syndrome and studied the patterns of X chromosome inactivation (XCI) in each girl.
We discovered in the 5'-UTR (untranslated region) of MECP2 mRNA a highly conserved G-quadruplex which overlapped a known deletion in Rett syndrome patients with decreased levels of MeCP2 protein.
We describe here the first case of MECP2-related severe neonatal encephalopathy caused by a mutation in exon one of MECP2, a mutation rarely identified in females with RTT.
We describe an Mecp2 allelic series representing the three most common missense Rett syndrome (RTT) mutations, including first reports of Mecp2[R133C] and Mecp2[T158M] knock-in mice, in addition to Mecp2[R306C] mutant mice.
We demonstrated for the first time that RTT is associated with a dysbiosis of both the bacterial and fungal component of the gut microbiota, suggesting that impairments of MeCP2 functioning favour the establishment of a microbial community adapted to the costive gastrointestinal niche of RTT subjects.
We conducted a nationwide survey to determine the prevalence of common gastrointestinal and nutritional disorders in Rett syndrome (RTT) based on parental reporting and related the occurrence of these problems to age and methyl-CpG-binding protein 2 (MECP2) gene status.
We conclude that Tubastatin A is capable of counteracting the microtubule defects observed in MeCP2-deficient cells, which could in turn lead to the restoration of molecular trafficking along the microtubules and thus could be a potentially new therapeutic option for RTT.
We conclude that only a subgroup of girls with possible RTT and no detectable mutation in the sequencing of the MECP2 gene do really have classical RTT.
We conclude that many individuals with MECP2 mutation exhibit characteristics that should raise suspicion for RTT, prior to evolution of the core clinical criteria.
We conclude that MECP2 mutations (missense or late truncating) can be found in girls with an IQ close to 45 and a clinical history of PSV of Rett syndrome.