ArticleNeurology. Genetics2023
Distinguishing Loss-of-Function and Gain-of-Function
Article in Neurology. Genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- Investigating genetic susceptibility to concussion through rare variants in ion channel and neurotransmission genes.Journal of neurology · 2026Article
- Genetic landscape of pediatric seizures in Southeast China: identification of a novel GLI3 frameshift variant through whole-exome sequencing.Annals of medicine and surgery (2012) · 2026Article
- Gene-specific pathogenicity predictor for chromatin remodeling BAF complex-associated neurodevelopmental disorders.HGG advances · 2026Article
- Evaluation, Diagnosis, and Treatment of Concomitant Movement Disorders in Genetic Epilepsies.Epilepsy currents · 2025Review
- A splice-switching antisense oligonucleotide approach for pediatric genetic epilepsies.bioRxiv : the preprint server for biology · 2025Article
- Article
- Gene Specific Pathogenicity Predictor for Chromatin-Remodeling BAF Complex-Associated Neurodevelopmental Disorders.bioRxiv : the preprint server for biology · 2025Article
- A research roadmap for SCN8A-related disorders: addressing knowledge gaps and aligning research priorities across stakeholders.Orphanet journal of rare diseases · 2025Article
- Deciphering the Natural History ofNeurology · 2025Article
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Morphological traits and machine learning for genetic lineage prediction of two reef-building corals.PloS one · 2025Article
- Unraveling the Link: Seizure Characteristics and Ammonia Levels in Urea Cycle Disorder During Hyperammonemic Crises.Pediatric neurology · 2024Observational
- Machine learning models reveal distinct disease subgroups and improve diagnostic and prognostic accuracy for individuals with pathogenic SCN8A gain-of-function variants.Biology open · 2024Article
- Genetic Advancements in Infantile Epileptic Spasms Syndrome and Opportunities for Precision Medicine.Genes · 2024Review
- Patient leadership and partnerships accelerate therapies for SCN8A and other developmental and epileptic encephalopathies.Therapeutic advances in rare diseaseReview
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background and Objectives: Pathogenic variants at the voltage-gated sodium channel gene, Methods: We performed an exhaustive search for individuals deemed to carry SCN8A GOF and LOF variants by means of in vitro studies in heterologous cell systems, or because the variant was classified as truncating, and recorded clinical features. This resulted in a total of 69 LOF variants: 34 missense and 35 truncating variants, including 9 nonsense, 13 frameshift, 6 splice site, 6 indels, and 1 large deletion. We then assembled a truth set of variants with known functional effects, excluding individuals carrying variants at other loci associated with epilepsy. We then trained a predictive model based on random forest using this truth set of 45 LOF variants and 45 GOF variants randomly selected from a set of variants tested by in vitro methods. Results: Phenotypic categories assigned to individuals correlated strongly with GOF or LOF variants. All patients with GOF variants experienced early-onset seizures (mean age at onset = 4.5 ± 3.1 months) while only 64.4% patients with LOF variants had seizures, most of which were late-onset absence seizures (mean age at onset = 40.0 ± 38.1 months). With high accuracy (95.4%), our model including 5 key clinical features classified individuals with GOF and LOF variants into 2 distinct cohorts differing in age at seizure onset, development of seizures, seizure type, intellectual disability, and developmental and epileptic encephalopathy. Discussion: The results support the hypothesis that patients with
Identifiers
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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.