ArticleThe Journal of clinical endocrinology and metabolism2018
Ezh2 Mutations Found in the Weaver Overgrowth Syndrome Cause a Partial Loss of H3K27 Histone Methyltransferase Activity.
Article in The Journal of clinical endocrinology and metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 51 citations in OpenAlex.
- Transgenerational inheritance of altered H3K27me3 in wild-type Caenorhabditis elegans.The EMBO journal · 2026Article
- From chromatin dynamics to brain disease: Polycomb-Trithorax mechanisms in neurodevelopment.Trends in neurosciences · 2026Review
- Unbalanced chromatin binding of Polycomb complexes drives neurodevelopmental disorders.Molecular cell · 2026Article
- Effects of Spin4 ablation in aging mice: body composition, bone density, and malignancy prevalence.bioRxiv : the preprint server for biology · 2026Article
- Convergent DNA methylation abnormalities at enhancers and bivalent promoters in human growth disorders.Epigenetics & chromatin · 2025Article
- From Overgrowth to Complex Malformations: A NovelChildren (Basel, Switzerland) · 2025Article
- Dominant-negative effects of Weaver syndrome-associated EZH2 variants.Genes & development · 2025Article
- Review
- Biological mechanism and immune response of MHC-II expression in tumor cells.Cancer biology & medicine · 2025Review
- Developmental stage and cellular context determine oncogenic and molecular outcomes ofBlood neoplasia · 2025Article
- Molecular Regulation of Palatogenesis and Clefting: An Integrative Analysis of Genetic, Epigenetic Networks, and Environmental Interactions.International journal of molecular sciences · 2025Review
- EZH2-dependent epigenetic reprogramming in the central nucleus of amygdala regulates adult anxiety in both sexes after adolescent alcohol exposure.Translational psychiatry · 2024Article
- BAP1 is required prenatally for differentiation and maintenance of postnatal murine enteric nervous system.The Journal of clinical investigation · 2024Article
- Expanding the Phenotypic and Genotypic Spectrum of Weaver Syndrome: A Missense Variant of theMolecular syndromology · 2024Article
- Epigenetic Causes of Overgrowth Syndromes.The Journal of clinical endocrinology and metabolism · 2024Review
- A mouse model of Weaver syndrome displays overgrowth and excess osteogenesis reversible with KDM6A/6B inhibition.JCI insight · 2024Article
- Epigenetic regulation of craniofacial development and disease.Birth defects research · 2024Review
- Growth disorders caused by variants in epigenetic regulators: progress and prospects.Frontiers in endocrinology · 2024Review
- Article
- Rare diseases of epigenetic origin: Challenges and opportunities.Frontiers in genetics · 2023Review
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 4 institutions in 2 countries.
Funding
Abstract
Context: Weaver syndrome is characterized by tall stature, advanced bone age, characteristic facies, and variable intellectual disability. It is caused by heterozygous mutations in enhancer of zeste homolog 2 (EZH2), a histone methyltransferase responsible for histone H3 at lysine 27 (H3K27) trimethylation. However, no early truncating mutations have been identified, suggesting that null mutations do not cause Weaver syndrome. Objective: To test alternative hypotheses that EZH2 variants found in Weaver syndrome cause either a gain of function or a partial loss of function. Design: Exome sequencing was performed in a boy with tall stature, advanced bone age, and mild dysmorphic features. Mutant or wild-type EZH2 protein was expressed in mouse growth plate chondrocytes with or without endogenous EZH2, and enzymatic activity was measured. A mouse model was generated, and histone methylation was assessed in heterozygous and homozygous embryos. Results: A de novo missense EZH2 mutation [c.1876G>A (p.Val626Met)] was identified in the proband. When expressed in growth plate chondrocytes, the mutant protein showed decreased histone methyltransferase activity. A mouse model carrying this EZH2 mutation was generated using CRISPR/Cas9. Homozygotes showed perinatal lethality, whereas heterozygotes were viable, fertile, and showed mild overgrowth. Both homozygous and heterozygous embryos showed decreased H3K27 methylation. Conclusion: We generated a mouse model with the same mutation as our patient, found that it recapitulates the Weaver overgrowth phenotype, and demonstrated that EZH2 mutations found in Weaver syndrome cause a partial loss of function.
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.