ArticleNPJ genomic medicine2021
Deficiency of TET3 leads to a genome-wide DNA hypermethylation episignature in human whole blood.
Article in NPJ genomic medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 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
22 citing papers in PubMed, 26 citations in OpenAlex.
- Clinical Epigenomics in Rare Diseases: Interpreting DNA Methylation Episignatures.Molecular genetics & genomic medicine · 2026Review
- Caring for Rare Genetic Disease: A Vision for the Future.Journal of genetic counseling · 2026Article
- Discovery of a DNA methylation episignature for Weiss-Kruszka syndrome.Human genetics · 2026Article
- Evolutionarily conserved short linear motifs drive actin filament binding.Nature cell biology · 2026Article
- Molecular interactome of HNRNPU reveals regulatory networks in neuronal differentiation and DNA methylation.Nucleic acids research · 2026Article
- Identification of an episignature for the MEF2C-associated syndrome.European journal of human genetics : EJHG · 2026Article
- Analysis Methods for Diagnosing Rare Neurodevelopmental Diseases with Episignatures: A Systematic Review of the Literature.Biomedicines · 2025Review
- Molecular genetic testing and cohort analysis of 32 twin pairs with neurodevelopmental disorders-Reporting a novel de novo variant of TET3.Human genomics · 2025Article
- Transposition element MERVL regulates DNA demethylation through TET3 in oxidative-damaged mouse preimplantation embryos.Molecular medicine (Cambridge, Mass.) · 2025Article
- Transcription factor occupancy limits DNA methylation and determines ICAM1 expression in breast cancer.Acta biochimica et biophysica Sinica · 2025Article
- Alterations in DNA 5-hydroxymethylation patterns in the hippocampus of an experimental model of chronic epilepsy.Neurobiology of disease · 2024Article
- Diagnostic utility of DNA methylation analysis in genetically unsolved pediatric epilepsies and CHD2 episignature refinement.Nature communications · 2024Article
- Clinical and genetic characteristics of ALS patients with variants in genes regulating DNA methylation.Journal of neurology · 2024Article
- Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice.Genome research · 2024Article
- Chromatinopathies: insight in clinical aspects and underlying epigenetic changes.Journal of applied genetics · 2024Review
- Five years of experience in the Epigenetics and Chromatin Clinic: what have we learned and where do we go from here?Human genetics · 2024Article
- A mouse model of Weaver syndrome displays overgrowth and excess osteogenesis reversible with KDM6A/6B inhibition.JCI insight · 2024Article
- Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice.bioRxiv : the preprint server for biology · 2023Article
- Review
- SHFLD3 phenotypes caused by 17p13.3 triplication/ duplication encompassing Fingerin (BHLHA9) invariably.Orphanet journal of rare diseases · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
34 authors at 17 institutions in 6 countries.
Funding
Abstract
TET3 encodes an essential dioxygenase involved in epigenetic regulation through DNA demethylation. TET3 deficiency, or Beck-Fahrner syndrome (BEFAHRS; MIM: 618798), is a recently described neurodevelopmental disorder of the DNA demethylation machinery with a nonspecific phenotype resembling other chromatin-modifying disorders, but inconsistent variant types and inheritance patterns pose diagnostic challenges. Given TET3's direct role in regulating 5-methylcytosine and recent identification of syndrome-specific DNA methylation profiles, we analyzed genome-wide DNA methylation in whole blood of TET3-deficient individuals and identified an episignature that distinguishes affected and unaffected individuals and those with mono-allelic and bi-allelic pathogenic variants. Validation and testing of the episignature correctly categorized known TET3 variants and determined pathogenicity of variants of uncertain significance. Clinical utility was demonstrated when the episignature alone identified an affected individual from over 1000 undiagnosed cases and was confirmed upon distinguishing TET3-deficient individuals from those with 46 other disorders. The TET3-deficient signature - and the signature resulting from activating mutations in DNMT1 which normally opposes TET3 - are characterized by hypermethylation, which for BEFAHRS involves CpG sites that may be biologically relevant. This work expands the role of epi-phenotyping in molecular diagnosis and reveals genome-wide DNA methylation profiling as a quantitative, functional readout for characterization of this new biochemical category of disease.
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.