ArticleClinical epigenetics2021
Childhood-onset dystonia-causing KMT2B variants result in a distinctive genomic hypermethylation profile.
Article in Clinical epigenetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 33 citations in OpenAlex.
- Clinical, imaging and genetic profile of KMT2B-related dystonia: a review of published cases.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Data-Driven Insights into Hyperkinetic Disorders in Neurodevelopmental Syndromes and Epileptic Encephalopathies.Movement disorders clinical practice · 2026Review
- Review
- Dystonia: Insights into Mechanisms and Novel Therapeutics.Current neurology and neuroscience reports · 2026Review
- Central precocious puberty as the initial manifestation of multisystem involvement caused byFrontiers in endocrinology · 2026Article
- Analysis Methods for Diagnosing Rare Neurodevelopmental Diseases with Episignatures: A Systematic Review of the Literature.Biomedicines · 2025Review
- Novel heterozygous mutation in KMT2B causing an unusual phenotypic presentation: a comprehensive clinical and bioinformatic analysis.Molecular biology reports · 2025Article
- Article
- Biallelic loss-of-function variants in ZNF142 are associated with a robust DNA methylation signature affecting a limited number of genomic loci.European journal of human genetics : EJHG · 2025Article
- Pediatric Genetic Dystonias: Current Diagnostic Approaches and Treatment Options.Life (Basel, Switzerland) · 2025Review
- Article
- DNA methylation profiling in Kabuki syndrome: reclassification of germline KMT2D VUS and sensitivity in validating postzygotic mosaicism.European journal of human genetics : EJHG · 2024Article
- Narrowing the diagnostic gap: Genomes, episignatures, long-read sequencing, and health economic analyses in an exome-negative intellectual disability cohort.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Next-generation sequencing and bioinformatics in rare movement disorders.Nature reviews. Neurology · 2024Review
- Diagnostic utility of DNA methylation episignature analysis for early diagnosis of KMT2B-related disorders: case report.Frontiers in genetics · 2024Article
- Response to: Are there two disjunct episignatures for KMT2B-related disease?Brain communications · 2024Article
- Epigenotype-genotype-phenotype correlations in SETD1A and SETD2 chromatin disorders.Human molecular genetics · 2023Review
- Identification of a robust DNA methylation signature for Fanconi anemia.American journal of human genetics · 2023Article
- KMT2B-Related Dystonia in Indian Patients With Literature Review and Emphasis on Asian Cohort.Journal of movement disorders · 2023Article
- Germline pathogenic variants in HNRNPU are associated with alterations in blood methylome.European journal of human genetics : EJHG · 2023Article
Corrections and comments
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Authors and funding
27 authors at 9 institutions in 3 countries.
Funding
Abstract
backgroundDystonia is a clinically and genetically heterogeneous movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements and/or postures. Heterozygous variants in lysine methyltransferase 2B (KMT2B), encoding a histone H3 methyltransferase, have been associated with a childhood-onset, progressive and complex form of dystonia (dystonia 28, DYT28). Since 2016, more than one hundred rare KMT2B variants have been reported, including frameshift, nonsense, splice site, missense and other in-frame changes, many having an uncertain clinical impact.
resultsWe characterize the genome-wide peripheral blood DNA methylation profiles of a cohort of 18 patients with pathogenic and unclassified KMT2B variants. We resolve the "episignature" associated with KMT2B haploinsufficiency, proving that this approach is robust in diagnosing clinically unsolved cases, properly classifying them with respect to other partially overlapping dystonic phenotypes, other rare neurodevelopmental disorders and healthy controls. Notably, defective KMT2B function in DYT28 causes a non-random DNA hypermethylation across the genome, selectively involving promoters and other regulatory regions positively controlling gene expression.
conclusionsWe demonstrate a distinctive DNA hypermethylation pattern associated with DYT28, provide an epigenetic signature for this disorder enabling accurate diagnosis and reclassification of ambiguous genetic findings and suggest potential therapeutic approaches.
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