ArticleJournal of human genetics2019
Novel mutations in KMT2B offer pathophysiological insights into childhood-onset progressive dystonia.
Article in Journal of human genetics, 2019. 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, 1 of them a synthesis that pooled it.
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, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Identification of a novel de novo KMT2B variant in a Greek dystonia patient via exome sequencing genotype-phenotype correlations of all published cases.Molecular biology reports · 2021Pooled it
- Genetic analysis of childhood-onset dystonia-28 caused by a variant (c.5076G>A) in theGlobal medical genetics · 2026Article
- Clinical, imaging and genetic profile of KMT2B-related dystonia: a review of published cases.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Article
- Novel Genetic and Phenotypic Expansion inGenes · 2023Article
- KMT2B-Related Dystonia in Indian Patients With Literature Review and Emphasis on Asian Cohort.Journal of movement disorders · 2023Article
- Genome sequencing and comprehensive rare-variant analysis of 465 families with neurodevelopmental disorders.American journal of human genetics · 2023Article
- GPi DBS treatment outcome in children with monogenic dystonia: a case series and review of the literature.Frontiers in neurology · 2023Article
- Zinc finger myeloid Nervy DEAF-1 type (ZMYND) domain containing proteins exert molecular interactions to implicate in carcinogenesis.Discover oncology · 2022Review
- Early-onset generalized dystonia caused by a new mutation in the KMT2B gene: Case reportBiomedica : revista del Instituto Nacional de Salud · 2022Article
- GPi-DBS forMovement disorders clinical practice · 2022Review
- Genetic Dystonias: Update on Classification and New Genetic Discoveries.Current neurology and neuroscience reports · 2021Review
- Association of TOR1A and GCH1 Polymorphisms with Isolated Dystonia in India.Journal of molecular neuroscience : MN · 2021Article
- KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation.Brain : a journal of neurology · 2020Article
- The clinical-phenotype continuum in DYNC1H1-related disorders-genomic profiling and proposal for a novel classification.Journal of human genetics · 2020Article
- Radiofrequency ablation for DYT-28 dystonia: short term follow-up of three adult cases.Annals of clinical and translational neurology · 2020Article
- Failure to thrive - an overlooked manifestation of KMT2B-related dystonia: a case presentation.BMC neurology · 2020Article
- Pallidal Deep Brain Stimulation for Monogenic Dystonia: The Effect of Gene on Outcome.Frontiers in neurology · 2020Review
- Bi-allelic mutations in uncoordinated mutant number-45 myosin chaperone B are a cause for congenital myopathy.Acta neuropathologica communications · 2019Article
- Update on KMT2B-Related Dystonia.Current neurology and neuroscience reports · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
Rapid progress has recently been made in the elucidation of the genetic basis of childhood-onset inherited generalized dystonia (IGD) due to the implementation of genomic sequencing methodologies. We identified four patients with childhood-onset IGD harboring novel disease-causing mutations in lysine-specific histone methyltransferase 2B gene (KMT2B) by whole-exome sequencing. The main focus of this paper is to gain novel pathophysiological insights through understanding the molecular consequences of these mutations. The disease course is mostly progressive, evolving from lower limbs into generalized dystonia, which could be associated with dysarthria, dysphonia, intellectual disability, orofacial dyskinesia, and sometimes distinct dysmorphic facial features. In two patients, motor performances improved after bilateral implantation of deep brain stimulation in the globus pallidus internus (GPi-DBS). Pharmacotherapy with trihexyphenidyl reduced dystonia in two patients. We discovered three novel KMT2B mutations. Our analyses revealed that the mutation in patient 1 (c.7463A > G, p.Y2488C) is localized in the highly conserved FYRC domain of KMT2B. This mutation holds the potential to alter the inter-domain FYR interactions, which could lead to KMT2B instability. The mutations in patients 2 and 3 (c.3596_3697insC, p.M1202Dfs*22; c.4229delA, p.Q1410Rfs*12) lead to predicted unstable transcripts, likely to be subject to degradation by non-sense-mediated decay. Childhood-onset progressive dystonia with orofacial involvement is one of the main clinical manifestations of KMT2B mutations. In all, 26% (18/69) of the reported cases have T2 signal alterations of the globus pallidus internus, mostly at a younger age. Anticholinergic medication and GPi-DBS are promising treatment options and shall be considered early.
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.