ArticleProceedings of the National Academy of Sciences of the United States of America1999
The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 280 papers.
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Who cites it
280 citing papers in PubMed, 725 citations in OpenAlex.
- Abnormal Hypermethylation at Imprinting Control Regions in Patients with S-Adenosylhomocysteine Hydrolase (AHCY) Deficiency.PloS one · 2016Trial
- Multidomain interaction governs the filamentous assembly of the dominant-negative DNMT3A R882H mutant.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Functional characterization of UHRF1 variants in facilitating DNA methylation.The Journal of biological chemistry · 2026Article
- Recent Advances in Searching for DNMT Inhibitors and Their Potential Application in Treating Human Diseases.International journal of molecular sciences · 2026Review
- Structure of human lymphoid-specific helicase HELLS in its autoinhibited state.Nucleic acids research · 2026Article
- Cutaneous Manifestations of Inborn Errors of Immunity: Clinical Clues to Immune Disorders.Medicina (Kaunas, Lithuania) · 2026Review
- A role of protein conformational dynamics in mammalian DNA methylation.Structural dynamics (Melville, N.Y.) · 2026Review
- Transcriptional PBR cycles at pericentromeric repeats cause gross chromosomal rearrangements through Rad52-dependent ADR-loop formation.Nucleic acids research · 2026Article
- ICF syndrome: An epigenetic paradigm for primary immunodeficiencies.Journal of human immunity · 2026Review
- Clinical immunology in chromatinopathies: a scoping review.Frontiers in immunology · 2026Article
- Structure of human lymphoid-specific helicase HELLS in its autoinhibitory state.bioRxiv : the preprint server for biology · 2025Article
- Decitabine-mediated DNA methylation dynamics at pericentromeric satellite 2 repeats.BMC cancer · 2025Article
- Diversity challenges and reconciles genetics in facioscapulohumeral muscular dystrophy.Journal of human genetics · 2025Review
- The ZBTB24-CDCA7-HELLS axis suppresses the totipotent 2C-like reprogramming by maintaining Dux methylation and repression.Nucleic acids research · 2025Article
- ZBTB24 is a conserved multifaceted transcription factor at genes and centromeres that governs the DNA methylation state and expression of satellite repeats.Human molecular genetics · 2025Article
- In-depth immune profiling of a patient with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2 caused by a novel mutation in ZBTB24.Clinical and experimental immunology · 2025Article
- Tissue-specific roles of de novo DNA methyltransferases.Epigenetics & chromatin · 2025Review
- Molecular mechanisms for DNA methylation defects induced by ICF syndrome-linked mutations in DNMT3B.Protein science : a publication of the Protein Society · 2024Article
- The Role of DNMT Methyltransferases and TET Dioxygenases in the Maintenance of the DNA Methylation Level.Biomolecules · 2024Review
- The ICF syndrome protein CDCA7 harbors a unique DNA binding domain that recognizes a CpG dyad in the context of a non-B DNA.Science advances · 2024Article
220 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
DNA methylation is an important regulator of genetic information in species ranging from bacteria to humans. DNA methylation appears to be critical for mammalian development because mice nullizygous for a targeted disruption of the DNMT1 DNA methyltransferase die at an early embryonic stage. No DNA methyltransferase mutations have been reported in humans until now. We describe here the first example of naturally occurring mutations in a mammalian DNA methyltransferase gene. These mutations occur in patients with a rare autosomal recessive disorder, which is termed the ICF syndrome, for immunodeficiency, centromeric instability, and facial anomalies. Centromeric instability of chromosomes 1, 9, and 16 is associated with abnormal hypomethylation of CpG sites in their pericentromeric satellite regions. We are able to complement this hypomethylation defect by somatic cell fusion to Chinese hamster ovary cells, suggesting that the ICF gene is conserved in the hamster and promotes de novo methylation. ICF has been localized to a 9-centimorgan region of chromosome 20 by homozygosity mapping. By searching for homologies to known DNA methyltransferases, we identified a genomic sequence in the ICF region that contains the homologue of the mouse Dnmt3b methyltransferase gene. Using the human sequence to screen ICF kindreds, we discovered mutations in four patients from three families. Mutations include two missense substitutions and a 3-aa insertion resulting from the creation of a novel 3' splice acceptor. None of the mutations were found in over 200 normal chromosomes. We conclude that mutations in the DNMT3B are responsible for the ICF syndrome.
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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.