ArticleNeurology2013
DNMT1 mutation hot spot causes varied phenotypes of HSAN1 with dementia and hearing loss.
Article in Neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 68 citations in OpenAlex.
- Recent Advances in Searching for DNMT Inhibitors and Their Potential Application in Treating Human Diseases.International journal of molecular sciences · 2026Review
- [Current status and future perspectives on age-related hearing loss and cognitive impairment].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2026Review
- Functional and Epigenomic Consequences ofInternational journal of molecular sciences · 2026Article
- Epigenetic Modifications in Sensorineural Hearing Loss: Protective Mechanisms and Therapeutic Potential.Current medical science · 2025Review
- Chromatin modifiers in neurodevelopment.Frontiers in molecular neuroscience · 2025Review
- DINGO: increasing the power of locus discovery in maternal and fetal genome-wide association studies of perinatal traits.Nature communications · 2024Article
- The Role of DNMT Methyltransferases and TET Dioxygenases in the Maintenance of the DNA Methylation Level.Biomolecules · 2024Review
- Mechanisms of DNA Methylation Regulatory Function and Crosstalk with Histone Lysine Methylation.Journal of molecular biology · 2024Review
- Advanced Omics Techniques for Understanding Cochlear Genome, Epigenome, and Transcriptome in Health and Disease.Biomolecules · 2023Review
- Article
- Novel de novo DNMT1 gene mutation associated with hereditary sensory and autonomic neuropathy 1E (HSAN1E).Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Article
- Germline Abnormalities in DNA Methylation and Histone Modification and Associated Cancer Risk.Current hematologic malignancy reports · 2022Review
- DNA Methylation Episignatures in Neurodevelopmental Disorders Associated with Large Structural Copy Number Variants: Clinical Implications.International journal of molecular sciences · 2022Review
- Untangling neurodevelopmental disorders in the adulthood: a movement disorder is the clue.Orphanet journal of rare diseases · 2022Article
- Cerebellar Ataxia as a Common Clinical Presentation Associated with DNMT1 p.Y511H and a Review of the Literature.Journal of molecular neuroscience : MN · 2021Review
- Chromatin Alterations in Neurological Disorders and Strategies of (Epi)Genome Rescue.Pharmaceuticals (Basel, Switzerland) · 2021Review
- A long intergenic non-coding RNA regulates nuclear localization of DNA methyl transferase-1.iScience · 2021Article
- Expanded genetic insight and clinical experience of DNMT1-complex disorder.Neurology. Genetics · 2020Article
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- Review
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundMutations in DNA methyltransferase 1 (DNMT1) have been identified in 2 autosomal dominant syndromes: 1) hereditary sensory autonomic neuropathy with dementia and hearing loss (HSAN1E); and 2) cerebellar ataxia, deafness, and narcolepsy. Both syndromes have mutations in targeting sequence (TS) domain (exons 20-21), which is important in mediating DNA substrate binding to the DNMT1 catalytic domain. Frontal lobe hypometabolism has been documented in an HSAN1E family, but memory loss has been the primary cognitive complaint. The chromosomal location of the DNMT1 gene at 19p13.2 has been linked to familial late-onset Alzheimer disease.
methodsWe sequenced 41 exons of DNMT1 and their flanking regions in 1) 2 kindreds with HSAN1E; 2) 48 patients with HSAN1 alone without dementia and hearing loss; and 3) 5 probands of familial frontotemporal dementia (FTD) kindreds. We also sequenced exon 20 and 21 in 364 autopsy-confirmed late-onset Alzheimer disease cases.
resultsMutations in DNMT1 were specific to 2 HSAN1E kindreds with dementia and hearing loss (no narcolepsy). One family carried previously identified mutation Tyr495Cys; the other carried a novel Tyr495His, both in the TS domain. The symptoms of these patients include prominent personality, psychiatric manifestations, and seizures in one and the onset time is later than the previously reported cases.
conclusionClinicians should consider DNMT1 mutations in patients presenting with FTD or primary memory decline who also have sensory neuropathy and hearing loss. Amino acid Tyr495 is a hot spot for HSAN1E, distinct from exon 21 mutations associated with narcolepsy.
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