ArticleNature2013
De novo mutations in epileptic encephalopathies.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 857 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
857 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,534 citations in OpenAlex.
- Management of Lennox-Gastaut syndrome with deep brain stimulation: A systematic literature review.Neurosciences (Riyadh, Saudi Arabia) · 2022Pooled it
- Cys-loop receptors on cannabinoids: All high?Frontiers in physiology · 2022Pooled it
- Precision Medicine in Epilepsy: Diagnostic Yield by Next-Generation Sequencing and Genotype-Phenotype Findings in a Romanian Cohort.International journal of molecular sciences · 2026Article
- Genetic Diagnosis in Epilepsy: Implications for Clinical Management.Current neurology and neuroscience reports · 2026Review
- Cannabinoid tolerance relies on CBProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cannabidiol reduces atypical absence seizures and epileptic spasms in a Gabrb3Epilepsia open · 2026Article
- STXBP1 Variants Associated With Epilepsy With Variable Severity.CNS neuroscience & therapeutics · 2026Article
- Uncoupling memory impairments from autism-associated behaviors in Chd2 deficient mice.Molecular psychiatry · 2026Article
- A de novo Loss-of-function Variant in RAPGEF6 Supports its Role in Neuropsychiatric Disorders.Journal of molecular neuroscience : MN · 2026Article
- Virtual Screening and Zebrafish Phenotype-Based Evaluation Argues Against Repurposing 4-Phenylbutyrate for STXBP1-Related Disorders.Pharmacology research & perspectives · 2026Article
- Artificial intelligence in the assessment of epilepsy-related genetic mutations: Learned from GABAEpilepsia open · 2026Review
- Genomic Profiling of Adults with Pharmacoresistant Genetic Generalized Epilepsy.Brain sciences · 2026Article
- Virtual screening and zebrafish phenotype-based evaluation argues against repurposing 4-phenylbutyrate for STXBP1-related disorders.bioRxiv : the preprint server for biology · 2026Article
- The anti-NMDAR1 antibodies and IL-17 signaling pathway shape NMDAR encephalitis.Molecular psychiatry · 2026Article
- Genome sequencing boosts diagnostic yield for the developmental and epileptic encephalopathies.medRxiv : the preprint server for health sciences · 2026Article
- The economic burden of KCNT1-related disorders in the United States: insights from caregiver-reported and EMR-derived data.BMC health services research · 2026Article
- E3 Ubiquitin Ligase Nedd4-2 Exacerbates Seizure-Induced Mitochondrial Defects in an Alzheimer's Disease Mouse Model.Journal of neurochemistry · 2026Article
- Genotype and Age at Onset Drive Vermis Atrophy in CACNA1A- and GAA-FGF14-related Ataxias.Cerebellum (London, England) · 2026Article
- How copy number variations shape brain developmental disorders: Unraveling the synaptic puzzle.Psychiatry and clinical neurosciences · 2026Review
- Genetic Risk Factors for Epilepsy: From Familial Studies to Gene Discoveries and Polygenic Risk Scores, Strides Toward Unlocking an Age-Old Question in Epilepsy.Epilepsy currents · 2026Review
797 more citing papers are in PubMed but not listed here.
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83 authors at 1 institution in 1 country.
Funding
Abstract
Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the ∼4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 × 10(-3)). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 × 10(-10) and P = 7.8 × 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P < 10(-8)), as has been reported previously for autism spectrum 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.