Mutations in MECP2 cause classic or preserved speech variant Rett syndrome and intellectual disability in females and early demise or marked neurodevelopmental handicap in males.
In the present study, XCI patterns in patients and their mothers, parental origin of skewed X chromosome in patients, and the correlations between XCI, genotype, and phenotype were analyzed in 52 cases of RTT with MECP2 mutations, 50 RTT mothers, and 48 normal female controls.
Cross-sectional study of 245 girls and women with typical Rett syndrome seen between 1990 and 2004 in tertiary academic outpatient specialty clinics and who had complete MECP2 mutation analysis.
Females with the p.R306C or p.T158M mutations in the MECP2 gene were more likely to have an initial diagnosis of autism, and the specific Rett syndrome symptoms were noted at a later age.
Methyl CpG binding protein 2 (MeCP2) selectively binds to methylated DNA and mutations in the MECP2 cause the autism-spectrum neurodevelopmental disorder Rett syndrome.
Our data suggest that alterations in the affinity of MeCP2 for chromatin might contribute to the pathological effects of mutations causing Rett Syndrome.
MECP2 mutations were identified in 914 of 1059 participants (86%): 799 of 870 (92%) participants with typical Rett syndrome had an MECP2 mutation, 94 of 162 (58%) with atypical Rett syndrome had a mutation, and all 21 individuals diagnosed as Not Rett syndrome had a mutation.
This study reaffirms the view that large MECP2 deletions are an important cause of both classical and atypical RTT syndrome, and cautions that apparent deletions detected using high-throughput diagnostic techniques require further characterisation.
Correlation between clinical severity in patients with Rett syndrome with a p.R168X or p.T158M MECP2 mutation, and the direction and degree of skewing of X-chromosome inactivation.
Because of their involvement in cell differentiation and neural development, ID genes are ideal primary targets for MeCP2 regulation of neuronal maturation that may explain the molecular pathogenesis of RTT.
Mice expressing a truncated allele of Mecp2 (Mecp2(308)) reproduce the motor and social behavior abnormalities of RTT; however, it is not known whether learning deficits are present in these animals.
The discovery that Rett syndrome is caused by mutations that affect the methyl-CpG-binding protein MeCP2 provided a major breakthrough in understanding this severe neurodevelopmental disorder.
Initial hypotheses indicating that the MeCP2 protein acts as a genome-wide transcriptional repressor were not confirmed by global gene expression studies in various tissues of individuals with RTT and mouse models of MeCP2 deficiency.
Given that this is a minimum incidence because complete inventory was not possible, this study of patients with Rett syndrome reinforces the fact that the great majority of patients with Rett syndrome have a MECP2 mutation.