ArticleScientific reports2016
From Function to Phenotype: Impaired DNA Binding and Clustering Correlates with Clinical Severity in Males with Missense Mutations in MECP2.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- Beyond Rett syndrome: a case series expanding the neurological spectrum associated with pathogenic MECP2 variants.Journal of neurology · 2026Article
- MeCP2 NID interaction with RNA: implications for Rett syndrome-relevant protein regulation.Human molecular genetics · 2026Article
- MeCP2-driven chromatin organization controls nuclear stiffness.Communications biology · 2025Article
- Testing the PEST hypothesis using relevant Rett mutations in MeCP2 E1 and E2 isoforms.Human molecular genetics · 2024Article
- Multilevel evidence of MECP2-associated mitochondrial dysfunction and its therapeutic implications.Frontiers in psychiatry · 2023Article
- The Chromatin Structure at theInternational journal of molecular sciences · 2022Article
- Wide spectrum of neuronal and network phenotypes in human stem cell-derived excitatory neurons with Rett syndrome-associated MECP2 mutations.Translational psychiatry · 2022Article
- Recommendations by the ClinGen Rett/Angelman-like expert panel for gene-specific variant interpretation methods.Human mutation · 2022Article
- Disruption of MeCP2-TCF20 complex underlies distinct neurodevelopmental disorders.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Transcriptomic and Epigenomic Landscape in Rett Syndrome.Biomolecules · 2021Review
- MeCP2: The Genetic Driver of Rett Syndrome Epigenetics.Frontiers in genetics · 2021Review
- Review
- Interplay of LIS1 and MeCP2: Interactions and Implications With the Neurodevelopmental Disorders Lissencephaly and Rett Syndrome.Frontiers in cellular neuroscience · 2019Article
- MeCP2_E1 N-terminal modifications affect its degradation rate and are disrupted by the Ala2Val Rett mutation.Human molecular genetics · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
Mutations in the MECP2 gene cause Rett syndrome (RTT). MeCP2 binds to chromocentric DNA through its methyl CpG-binding domain (MBD) to regulate gene expression. In heterozygous females the variable phenotypic severity is modulated by non-random X-inactivation, thus making genotype-phenotype comparisons unreliable. However, genotype-phenotype correlations in males with hemizygousMECP2 mutations can provide more accurate insights in to the true biological effect of specific mutations. Here, we compared chromatin organization and binding dynamics for twelve MeCP2 missense mutations (including two novel and the five most common MBD missense RTT mutations) and identifiedacorrelation with phenotype in hemizygous males. We observed impaired interaction of MeCP2-DNA for mutations around the MBD-DNA binding interface, and defective chromatin clustering for distal MBD mutations. Furthermore, binding and mobility dynamics show a gradient of impairment depending on the amino acid properties and tertiary structure within the MBD. Interestingly, a wide range of phenotypic/clinical severity, ranging from neonatal encephalopathy to mild psychiatric abnormalities were observed and all are consistent with our functional/molecular results. Overall, clinical severity showed a direct correlation with the functional impairment of MeCP2. These mechanistic and phenotypic correlations of MeCP2 mutations will enable improved and individualized diagnostics, and may lead to personalized therapeutic interventions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.