ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
Computational analysis of 10,860 phenotypic annotations in individuals with SCN2A-related disorders.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 68 citations in OpenAlex.
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- Familial SYNGAP1 variants define the boundaries of a complex neurodevelopmental disorder with epilepsy.Epilepsia · 2025Article
- Conserved missense variant pathogenicity and correlated phenotypes across paralogous genes.Genome biology · 2025Article
- Variants in BSN, encoding the presynaptic protein Bassoon, result in a distinct neurodevelopmental disorder with a broad phenotypic range.American journal of human genetics · 2025Article
- Deciphering the Natural History ofNeurology · 2025Article
- Quantitative natural history modeling of HPDL-related disease based on cross-sectional data reveals genotype-phenotype correlations.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- A Longitudinal Exploration ofNeurology. Genetics · 2025Review
- DecipheringArXiv · 2024Article
- Natural language processing and expert follow-up establishes tachycardia association with CDKL5 deficiency disorder.Genetics in medicine open · 2024Article
- Healthcare utilization and clinical characteristics of genetic epilepsy in electronic health records.Brain communications · 2024Article
- Scn2a insufficiency alters spontaneous neuronal CaiScience · 2023Article
- Human iPSC-derived microglia sense and dampen hyperexcitability of cortical neurons carrying the epilepsy-associated SCN2A-L1342P mutation.bioRxiv : the preprint server for biology · 2023Article
- Individualised human phenotype ontology gene panels improve clinical whole exome and genome sequencing analytical efficacy in a cohort of developmental and epileptic encephalopathies.Molecular genetics & genomic medicine · 2023Article
- Enriching representation learning using 53 million patient notes through human phenotype ontology embedding.Artificial intelligence in medicine · 2023Article
- Predicting functional effects of ion channel variants using new phenotypic machine learning methods.PLoS computational biology · 2023Article
- Generalisable long COVID subtypes: findings from the NIH N3C and RECOVER programmes.EBioMedicine · 2023Article
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
purposePathogenic variants in SCN2A cause a wide range of neurodevelopmental phenotypes. Reports of genotype-phenotype correlations are often anecdotal, and the available phenotypic data have not been systematically analyzed.
methodsWe extracted phenotypic information from primary descriptions of SCN2A-related disorders in the literature between 2001 and 2019, which we coded in Human Phenotype Ontology (HPO) terms. With higher-level phenotype terms inferred by the HPO structure, we assessed the frequencies of clinical features and investigated the association of these features with variant classes and locations within the Na
resultsWe identified 413 unrelated individuals and derived a total of 10,860 HPO terms with 562 unique terms. Protein-truncating variants were associated with autism and behavioral abnormalities. Missense variants were associated with neonatal onset, epileptic spasms, and seizures, regardless of type. Phenotypic similarity was identified in 8/62 recurrent SCN2A variants. Three independent principal components accounted for 33% of the phenotypic variance, allowing for separation of gain-of-function versus loss-of-function variants with good performance.
conclusionOur work shows that translating clinical features into a computable format using a standardized language allows for quantitative phenotype analysis, mapping the phenotypic landscape of SCN2A-related disorders in unprecedented detail and revealing genotype-phenotype correlations along a multidimensional spectrum.
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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.