ArticleHuman molecular genetics2021
Rare deleterious de novo missense variants in Rnf2/Ring2 are associated with a neurodevelopmental disorder with unique clinical features.
Article in Human molecular genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 18 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.
The trial behind it
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.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Review
- Unbalanced chromatin binding of Polycomb complexes drives neurodevelopmental disorders.Molecular cell · 2026Article
- Article
- De novo variants in RYBP are associated with a severe neurodevelopmental disorder and congenital anomalies.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- Hao-Fountain syndrome protein USP7 controls neuronal differentiation via BCOR-ncPRC1.1.Genes & development · 2025Article
- Loss-of-function in RBBP5 results in a syndromic neurodevelopmental disorder associated with microcephaly.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- RING1 missense variants reveal sensitivity of DNA damage repair to H2A monoubiquitination dosage during neurogenesis.Nature communications · 2024Article
- H2A monoubiquitination: insights from human genetics and animal models.Human genetics · 2024Review
- Integrating non-mammalian model organisms in the diagnosis of rare genetic diseases in humans.Nature reviews. Genetics · 2024Review
- O-GlcNAcylation: the sweet side of epigenetics.Epigenetics & chromatin · 2023Review
- Rare de novo gain-of-function missense variants in DOT1L are associated with developmental delay and congenital anomalies.American journal of human genetics · 2023Article
- A de novo missense variant in EZH1 associated with developmental delay exhibits functional deficits in Drosophila melanogaster.Genetics · 2023Article
- Dominant-negative variants in CBX1 cause a neurodevelopmental disorder.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
- A concurrent dual analysis of genomic data augments diagnoses: Experiences of 2 clinical sites in the Undiagnosed Diseases Network.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
- Intellectual disability-associated disruption of O-GlcNAc cycling impairs habituation learning in Drosophila.PLoS genetics · 2022Article
- Invertebrate Model Organisms as a Platform to Investigate Rare Human Neurological Diseases.Experimental neurobiology · 2022Review
- Polycomb Repressive Complexes: Shaping Pancreatic Beta-Cell Destiny in Development and Metabolic Disease.Frontiers in cell and developmental biology · 2022Review
- Model organisms contribute to diagnosis and discovery in the undiagnosed diseases network: current state and a future vision.Orphanet journal of rare diseases · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
The Polycomb group (PcG) gene RNF2 (RING2) encodes a catalytic subunit of the Polycomb repressive complex 1 (PRC1), an evolutionarily conserved machinery that post-translationally modifies chromatin to maintain epigenetic transcriptional repressive states of target genes including Hox genes. Here, we describe two individuals, each with rare de novo missense variants in RNF2. Their phenotypes include intrauterine growth retardation, severe intellectual disabilities, behavioral problems, seizures, feeding difficulties and dysmorphic features. Population genomics data suggest that RNF2 is highly constrained for loss-of-function (LoF) and missense variants, and both p.R70H and p.S82R variants have not been reported to date. Structural analyses of the two alleles indicate that these changes likely impact the interaction between RNF2 and BMI1, another PRC1 subunit or its substrate Histone H2A, respectively. Finally, we provide functional data in Drosophila that these two missense variants behave as LoF alleles in vivo. The evidence provide support for deleterious alleles in RNF2 being associated with a new and recognizable genetic disorder. This tentative gene-disease association in addition to the 12 previously identified disorders caused by PcG genes attests to the importance of these chromatin regulators in Mendelian disorders.
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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.