ArticleJournal of human genetics2019
A comparative analysis of KMT2D missense variants in Kabuki syndrome, cancers and the general population.
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. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- Multicenter experience of Kabuki syndrome: a case series of eight patients including three novel KMT2D variants and a brief review.Neurogenetics · 2026Review
- A Diagnostic Dilemma: Concurrent Diagnosis of Cystic Fibrosis and Definitive Kabuki Syndrome Type 1.International journal of molecular sciences · 2026Article
- In utero rescue of neurological dysfunction in a mouse model of Wiedemann-Steiner syndrome.JCI insight · 2025Article
- Epigenome and transcriptome changes in KMT2D-related Kabuki syndrome Type 1 iPSCs, neuronal progenitors and cortical neurons.PLoS genetics · 2025Article
- Genomic analysis of 11,555 probands identifies 60 dominant congenital heart disease genes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes.American journal of human genetics · 2024Article
- DNA methylation profiling in Kabuki syndrome: reclassification of germline KMT2D VUS and sensitivity in validating postzygotic mosaicism.European journal of human genetics : EJHG · 2024Article
- Clinical and molecular characteristics of Kabuki syndrome patients with missense variants-novel features and literature review.Frontiers in genetics · 2024Article
- Peripheral blood DNA methylation and neuroanatomical responses to HDACi treatment that rescues neurological deficits in a Kabuki syndrome mouse model.Clinical epigenetics · 2023Article
- Molecular characterization of an embryonal rhabdomyosarcoma occurring in a patient with Kabuki syndrome: report and literature review in the light of tumor predisposition syndromes.Familial cancer · 2023Review
- Kabuki syndrome stem cell models reveal locus specificity of histone methyltransferase 2D (KMT2D/MLL4).Human molecular genetics · 2022Article
- Review
- Missense variants causing Wiedemann-Steiner syndrome preferentially occur in the KMT2A-CXXC domain and are accurately classified using AlphaFold2.PLoS genetics · 2022Article
- A Qualitative Study to Characterize the Humanistic Burden of Kabuki Syndrome in the United States and Canada.Advances in therapy · 2022Article
- Clinical heterogeneity of Kabuki syndrome in a cohort of Italian patients and review of the literature.European journal of pediatrics · 2022Review
- Neuroimaging in Kabuki syndrome and another KMT2D-related disorder.American journal of medical genetics. Part A · 2021Article
- Review
- Caregiver-reported clinical characteristics and the burden associated with Kabuki syndrome.American journal of medical genetics. Part A · 2020Article
- Phenotypic expansion of KMT2D-related disorder: Beyond Kabuki syndrome.American journal of medical genetics. Part A · 2020Article
- The Drosophila MLR COMPASS complex is essential for programming cis-regulatory information and maintaining epigenetic memory during development.Nucleic acids research · 2020Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Determining the clinical significance of germline and somatic KMT2D missense variants (MVs) in Kabuki syndrome (KS) and cancers can be challenging. We analysed 1920 distinct KMT2D MVs that included 1535 germline MVs in controls (Control-MVs), 584 somatic MVs in cancers (Cancer-MVs) and 201 MV in individuals with KS (KS-MVs). The proportion of MVs likely to affect splicing was significantly higher for Cancer-MVs and KS-MVs than in Control-MVs (p = 0.000018). Our analysis identified significant clustering of Cancer-MVs and KS-MVs in the PHD#3 and #4, RING#4 and SET domains. Areas of enrichment restricted to just Cancer-MVs (FYR-C and between amino acids 3043-3248) or KS-MVs (coiled-coil#5, FYR-N and between amino acids 4995-5090) were also found. Cancer-MVs and KS-MVs tended to affect more conserved residues (lower BLOSUM scores, p < 0.001 and p = 0.007). KS-MVs are more likely to increase the energy for protein folding (higher ELASPIC ∆∆G scores, p = 0.03). Cancer-MVs are more likely to disrupt protein interactions (higher StructMAn scores, p = 0.019). We reclassify several presumed pathogenic MVs as benign or as variants of uncertain significance. We raise the possibility of as yet unrecognised 'non-KS' phenotype(s) associated with some germline pathogenic KMT2D MVs. Overall, this work provides insights into the disease mechanism of KMT2D variants and can be extended to other genes, mutations in which also cause developmental syndromes and cancer.
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