ArticleEuropean journal of human genetics : EJHG2019
Spatially clustering de novo variants in CYFIP2, encoding the cytoplasmic FMRP interacting protein 2, cause intellectual disability and seizures.
Article in European journal of human genetics : EJHG, 2019. 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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39 citing papers in PubMed, 73 citations in OpenAlex.
- Impact of the CYFIP2 R87C variant in a human neuronal model in vitro.Scientific reports · 2026Article
- Molecular genotype-phenotype correlation in ACTB- and ACTG1-related non-muscle actinopathies.American journal of human genetics · 2026Article
- Time-resolved phenotyping of seizure evolution in developmental and epileptic encephalopathy: insights and gaps from the CYFIP2 Arg87Cys mouse model.Frontiers in synaptic neuroscience · 2026Review
- Cyfip2 mediates sensorimotor integration of visual input through Rac1-dependent actin remodeling.bioRxiv : the preprint server for biology · 2025Article
- Expanding the Phenotype ofAnnals of the Child Neurology Society · 2025Article
- Seizure evolution in a mouse model of West syndrome involves complex and time-dependent synapse remodeling, gliosis and alterations in lipid metabolism.PLoS biology · 2025Article
- Impact of Genetic Variants Associated with Neurodevelopmental Disorders on the WAVE Regulatory Complex.Journal of chemical information and modeling · 2025Article
- RNA m7G methylation regulators and targets significantly contribute to chronic obstructive pulmonary disease.Scientific reports · 2025Article
- ELK3-CYFIP2 axis-mediated actin remodeling modulates metastasis and natural killer cell responses in triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- The WAVE complex in developmental and adulthood brain disorders.Experimental & molecular medicine · 2025Review
- Case Report: An adult withFrontiers in psychiatry · 2025Article
- Common characteristics of variants linked to autism spectrum disorder in the WAVE regulatory complex.Frontiers in computational neuroscience · 2025Article
- Molecular basis of the CYFIP2 and NCKAP1 autism-linked variants in the WAVE regulatory complex.Protein science : a publication of the Protein Society · 2025Article
- Transcriptomic alterations in cortical astrocytes following the development of post-traumatic epilepsy.Scientific reports · 2024Article
- A novel variant in CYFIP2 in a girl with severe disabilities and bilateral perisylvian polymicrogyria.American journal of medical genetics. Part A · 2024Article
- Cyfip2 controls the acoustic startle threshold through FMRP, actin polymerization, and GABAbioRxiv : the preprint server for biology · 2024Article
- Article
- Orchestration of synaptic functions by WAVE regulatory complex-mediated actin reorganization.Experimental & molecular medicine · 2023Review
- The current benefit of genome sequencing compared to exome sequencing in patients with developmental or epileptic encephalopathies.Molecular genetics & genomic medicine · 2023Article
- Article
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Authors and funding
39 authors at 18 institutions in 8 countries.
Funding
Abstract
CYFIP2, encoding the evolutionary highly conserved cytoplasmic FMRP interacting protein 2, has previously been proposed as a candidate gene for intellectual disability and autism because of its important role linking FMRP-dependent transcription regulation and actin polymerization via the WAVE regulatory complex (WRC). Recently, de novo variants affecting the amino acid p.Arg87 of CYFIP2 were reported in four individuals with epileptic encephalopathy. We here report 12 independent patients harboring a variety of de novo variants in CYFIP2 broadening the molecular and clinical spectrum of a novel CYFIP2-related neurodevelopmental disorder. Using trio whole-exome or -genome sequencing, we identified 12 independent patients carrying a total of eight distinct de novo variants in CYFIP2 with a shared phenotype of intellectual disability, seizures, and muscular hypotonia. We detected seven different missense variants, of which two occurred recurrently (p.(Arg87Cys) and p.(Ile664Met)), and a splice donor variant in the last intron for which we showed exon skipping in the transcript. The latter is expected to escape nonsense-mediated mRNA decay resulting in a truncated protein. Despite the large spacing in the primary structure, the variants spatially cluster in the tertiary structure and are all predicted to weaken the interaction with WAVE1 or NCKAP1 of the actin polymerization regulating WRC-complex. Preliminary genotype-phenotype correlation indicates a profound phenotype in p.Arg87 substitutions and a more variable phenotype in other alterations. This study evidenced a variety of de novo variants in CYFIP2 as a novel cause of mostly severe intellectual disability with seizures and muscular hypotonia.
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