ArticleAmerican journal of human genetics2020
De Novo KAT5 Variants Cause a Syndrome with Recognizable Facial Dysmorphisms, Cerebellar Atrophy, Sleep Disturbance, and Epilepsy.
Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Clock gene dysregulation in epilepsy: A systematic review.Epilepsia open · 2026Pooled it
- Biallelic inactivating variants in the chromatin remodeler DMAP1 cause a syndromic neurodevelopmental disorder.The Journal of clinical investigation · 2026Article
- Kat5 cKO mouse replicates biological domain signatures associated with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Disruption of DNA Repair as an Emerging Epigenetic Mechanism Underlying Autism Spectrum Disorder.Current psychiatry reports · 2026Review
- KAT5: the epigenetic regulator of central nervous system diseases.Frontiers in molecular neuroscience · 2026Review
- Review
- The multitalented TIP60 chromatin remodeling complex: wearing many hats in epigenetic regulation, cell division and diseases.Epigenetics & chromatin · 2025Review
- Molecular and clinical aspects of histone-related disorders.Human genomics · 2025Review
- Variants in EP400, encoding a chromatin remodeler, cause epilepsy with neurodevelopmental disorders.American journal of human genetics · 2025Article
- Transcriptome Analysis of Porcine Immune Cells Stimulated by Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) andInternational journal of molecular sciences · 2024Article
- HBO1, a MYSTerious KAT and its links to cancer.Biochimica et biophysica acta. Gene regulatory mechanisms · 2024Review
- Structural insights into the human NuA4/TIP60 acetyltransferase and chromatin remodeling complex.Science (New York, N.Y.) · 2024Article
- MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature.American journal of human genetics · 2024Article
- KAT6A deficiency impairs cognitive functions through suppressing RSPO2/Wnt signaling in hippocampal CA3.Science advances · 2024Article
- Acetyltransferase in cardiovascular disease and aging.The journal of cardiovascular aging · 2024Article
- Null and missense mutations of ERI1 cause a recessive phenotypic dichotomy in humans.American journal of human genetics · 2023Article
- Neuropathological signatures revealed by transcriptomic and proteomic analysis in Pten-deficient mouse models.Scientific reports · 2023Article
- The Tip60/Ep400 chromatin remodeling complex impacts basic cellular functions in cranial neural crest-derived tissue during early orofacial development.International journal of oral science · 2023Article
- Article
- Tip60/KAT5 Histone Acetyltransferase Is Required for Maintenance and Neurogenesis of Embryonic Neural Stem Cells.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 4 countries.
Funding
Abstract
KAT5 encodes an essential lysine acetyltransferase, previously called TIP60, which is involved in regulating gene expression, DNA repair, chromatin remodeling, apoptosis, and cell proliferation; but it remains unclear whether variants in this gene cause a genetic disease. Here, we study three individuals with heterozygous de novo missense variants in KAT5 that affect normally invariant residues, with one at the chromodomain (p.Arg53His) and two at or near the acetyl-CoA binding site (p.Cys369Ser and p.Ser413Ala). All three individuals have cerebral malformations, seizures, global developmental delay or intellectual disability, and severe sleep disturbance. Progressive cerebellar atrophy was also noted. Histone acetylation assays with purified variant KAT5 demonstrated that the variants decrease or abolish the ability of the resulting NuA4/TIP60 multi-subunit complexes to acetylate the histone H4 tail in chromatin. Transcriptomic analysis in affected individual fibroblasts showed deregulation of multiple genes that control development. Moreover, there was also upregulated expression of PER1 (a key gene involved in circadian control) in agreement with sleep anomalies in all of the individuals. In conclusion, dominant missense KAT5 variants cause histone acetylation deficiency with transcriptional dysregulation of multiples genes, thereby leading to a neurodevelopmental syndrome with sleep disturbance, cerebellar atrophy, and facial dysmorphisms, and suggesting a recognizable syndrome.
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Registered trials
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