ArticleHuman mutation2014
Molecular analysis, pathogenic mechanisms, and readthrough therapy on a large cohort of Kabuki syndrome patients.
Article in Human mutation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Kabuki syndrome: a Chinese case series and systematic review of the spectrum of mutations.BMC medical genetics · 2015Pooled it
- Increased risk for severe peripheral arterial disease in Kabuki syndrome.Journal of vascular surgery cases and innovative techniques · 2026Article
- Loss of function of the zinc finger homeobox 4 gene, ZFHX4, underlies a neurodevelopmental disorder.American journal of human genetics · 2025Article
- Therapeutic Potential of Translational Readthrough at Disease-Associated Premature Termination Codons From Tumor Suppressor Genes.IUBMB life · 2025Review
- Clinical and molecular characteristics of Korean patients with Kabuki syndrome.Journal of human genetics · 2024Article
- Loss-of-function of the Zinc Finger Homeobox 4 (medRxiv : the preprint server for health sciences · 2024Article
- Mechanisms of DNA Methylation Regulatory Function and Crosstalk with Histone Lysine Methylation.Journal of molecular biology · 2024Review
- Treatability of the KMT2-Associated Neurodevelopmental Disorders Using Antisense Oligonucleotide-Based Treatments.Human mutation · 2024Review
- Case report of kabuki syndrome in a newborn caused by KMT2D gene mutation.Frontiers in pediatrics · 2024Article
- Molecular insights of KMT2D and clinical aspects of Kabuki syndrome type 1.Birth defects research · 2023Review
- Article
- Congenital hyperinsulinemic hypoglycemia (HH) requiring treatment as the presenting feature of Kabuki syndrome.Clinical case reports · 2023Article
- Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.Science advances · 2023Article
- Histone lysine methyltransferase-related neurodevelopmental disorders: current knowledge and saRNA future therapies.Frontiers in cell and developmental biology · 2023Review
- Identification of unique DNA methylation sites in Kabuki syndrome using whole genome bisulfite sequencing and targeted hybridization capture followed by enzymatic methylation sequencing.Journal of human genetics · 2022Article
- Kabuki syndrome stem cell models reveal locus specificity of histone methyltransferase 2D (KMT2D/MLL4).Human molecular genetics · 2022Article
- Statistical models of the genetic etiology of congenital heart disease.Current opinion in genetics & development · 2022Review
- NovelJournal of the Endocrine Society · 2022Article
- A novel complex genomic rearrangement affecting the KCNJ2 regulatory region causes a variant of Cooks syndrome.Human genetics · 2022Article
- Clinical heterogeneity of Kabuki syndrome in a cohort of Italian patients and review of the literature.European journal of pediatrics · 2022Review
Corrections and comments
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Authors and funding
39 authors at 20 institutions in 1 country.
Funding
Abstract
Kabuki syndrome (KS) is a multiple congenital anomalies syndrome characterized by characteristic facial features and varying degrees of mental retardation, caused by mutations in KMT2D/MLL2 and KDM6A/UTX genes. In this study, we performed a mutational screening on 303 Kabuki patients by direct sequencing, MLPA, and quantitative PCR identifying 133 KMT2D, 62 never described before, and four KDM6A mutations, three of them are novel. We found that a number of KMT2D truncating mutations result in mRNA degradation through the nonsense-mediated mRNA decay, contributing to protein haploinsufficiency. Furthermore, we demonstrated that the reduction of KMT2D protein level in patients' lymphoblastoid and skin fibroblast cell lines carrying KMT2D-truncating mutations affects the expression levels of known KMT2D target genes. Finally, we hypothesized that the KS patients may benefit from a readthrough therapy to restore physiological levels of KMT2D and KDM6A proteins. To assess this, we performed a proof-of-principle study on 14 KMT2D and two KDM6A nonsense mutations using specific compounds that mediate translational readthrough and thereby stimulate the re-expression of full-length functional proteins. Our experimental data showed that both KMT2D and KDM6A nonsense mutations displayed high levels of readthrough in response to gentamicin treatment, paving the way to further studies aimed at eventually treating some Kabuki patients with readthrough inducers.
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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.