ReviewAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics2018
Epigenetics and autism spectrum disorder: A report of an autism case with mutation in H1 linker histone HIST1H1E and literature review.
Review in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2018. 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 39 papers.
What it found
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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.
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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.
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Who cites it
39 citing papers in PubMed, 66 citations in OpenAlex.
- Spatially resolved mapping of histones reveals selective neuronal response in Rett syndrome.The FEBS journal · 2026Article
- A Rare Presentation of HIST1H1E Syndrome with Short Stature and Multiple Pituitary Hormone DeficienciesJournal of clinical research in pediatric endocrinology · 2026Article
- Histone H1 variants regulate neurodevelopmental transcriptional programs in autism with 16p11.2 deletion.Genome biology · 2026Article
- Article
- Integrative transcriptome-wide association analyses reveal PRKCG-linked GABAergic dysfunction in Fragile X-associated tremor/ataxia syndrome.Nature communications · 2026Article
- Salivary Transcriptome and Mitochondrial Analysis of Autism Spectrum Disorder Children Compared to Healthy Controls.NeuroSci · 2024Article
- Novel protein-truncating variants of a chromatin-modifying gene MSL2 in syndromic neurodevelopmental disorders.European journal of human genetics : EJHG · 2024Article
- BATF alleviates ox-LDL-induced HCAEC injury by regulating SIRT1 expression in coronary heart disease.PloS one · 2024Article
- Climate Stressors and Physiological Dysregulations: Mechanistic Connections to Pathologies.International journal of environmental research and public health · 2023Review
- A case report of a novel HIST1H1E mutation and a review of the bibliography to evaluate the genotype-phenotype correlations.Molecular genetics & genomic medicine · 2023Review
- Novel epigenetic molecular therapies for imprinting disorders.Molecular psychiatry · 2023Review
- Measures of Early-life Behavior and Later Psychopathology in the LifeCycle Project - EU Child Cohort Network: A Cohort Description.Journal of epidemiology · 2023Article
- Biochemical, Genetic and Clinical Diagnostic Approaches to Autism-Associated Inherited Metabolic Disorders.Genes · 2023Review
- Post-Translation Modifications and Mutations of Human Linker Histone Subtypes: Their Manifestation in Disease.International journal of molecular sciences · 2023Review
- Histone variants and chromatin structure, update of advances.Computational and structural biotechnology journal · 2023Review
- Complex Neuroimmune Involvement in Neurodevelopment: A Mini-Review.Journal of inflammation research · 2023Review
- Roles of histone acetylation sites in cardiac hypertrophy and heart failure.Frontiers in cardiovascular medicine · 2023Review
- Structural Mechanism of TAF-Iβ Chaperone Function on Linker Histone H1.10.Journal of molecular biology · 2022Article
- Article
- Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups.Nature genetics · 2022Article
Corrections and comments
- Erratum issuedErratum.2019
Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Genetic mutations in genes encoding proteins involved in epigenetic machinery have been reported in individuals with autism spectrum disorder (ASD), intellectual disability, congenital heart disease, and other disorders. H1 histone linker protein, the basic component in nucleosome packaging and chromatin organization, has not been implicated in human disease until recently. We report a de novo deleterious mutation of histone cluster 1 H1 family member e (HIST1H1E; c.435dupC; p.Thr146Hisfs*50), encoding H1 histone linker protein H1.4, in a 10-year-old boy with autism and intellectual disability diagnosed through clinical whole exome sequencing. The c.435dupC at the 3' end of the mRNA leads to a frameshift and truncation of the positive charge in the carboxy-terminus of the protein. An expression study demonstrates the mutation leads to reduced protein expression, supporting haploinsufficiency of HIST1H1E protein and loss of function as an underlying mechanism of dysfunction in the brain. Taken together with other recent cases with mutations of HIST1H1E in intellectual disability, the evidence supporting the link to causality in disease is strong. Our finding implicates the deficiency of H1 linker histone protein in autism. The systematic review of candidate genes implicated in ASD revealed that 42 of 215 (19.5%) genes are directly involved in epigenetic regulations and the majority of these genes belong to histone writers, readers, and erasers. While the mechanism of how haploinsufficiency of HIST1H1E causes autism is entirely unknown, our report underscores the importance of further study of the function of this protein and other histone linker proteins in brain development.
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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.