ArticleAmerican journal of human genetics2016
De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 2 of them syntheses that pooled it.
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Who cites it
139 citing papers in PubMed, 2 syntheses or guidelines pooled it, 299 citations in OpenAlex.
- Calcium channelopathies and intellectual disability: a systematic review.Orphanet journal of rare diseases · 2021Pooled it
- High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies.American journal of human genetics · 2017Pooled it
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease.bioRxiv : the preprint server for biology · 2026Article
- Ethnopharmacological relevance of Chinese medicinal materials and natural products in epilepsy: a critical multi-target review integrating neurons, glia and inflammatory signaling.Frontiers in pharmacology · 2026Review
- AExperimental and therapeutic medicine · 2025Article
- Multiple Chemical Sensitivity and the SLC Gene Superfamily: A Case-Control Study.International journal of molecular sciences · 2025Article
- Article
- Contractures of the Hands As a Prenatal Phenotype of CACNA1A-Related Disorder.Prenatal diagnosis · 2025Article
- Polymorphisms inGenes · 2025Article
- Clinical and functional characterization of the GABRB3 p.Met80Val variant in early-onset epilepsy with long-term follow-up.Italian journal of pediatrics · 2025Article
- The severity of SLC1A2-associated neurodevelopmental disorders correlates with transporter dysfunction.EBioMedicine · 2025Article
- Exploring the Genetic Etiology of Pediatric Epilepsy: Insights from Targeted Next-Generation Sequence Analysis.Molecular syndromology · 2025Article
- Phenotypic variability in cases with CACNA1A mutation.European journal of pediatrics · 2025Article
- Insights on the Shared Genetic Landscape of Neurodevelopmental and Movement Disorders.Current neurology and neuroscience reports · 2025Review
- Advances in genetic developmental and epileptic encephalopathies with movement disorders.Acta epileptologica · 2025Review
- In vitro human ion channel assays predictive of drug-induced seizure.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Review
- Exome sequencing in Nigerian children with early-onset epilepsy syndromes.Epilepsia open · 2025Article
- A biallelic mutation in CACNA2D2 associated with developmental and epileptic encephalopathy affects calcium channel-dependent as well as synaptic functions of αJournal of neurochemistry · 2025Article
79 more citing papers are in PubMed but not listed here.
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1 author.
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Abstract
Epileptic encephalopathies (EEs) are the most clinically important group of severe early-onset epilepsies. Next-generation sequencing has highlighted the crucial contribution of de novo mutations to the genetic architecture of EEs as well as to their underlying genetic heterogeneity. Our previous whole-exome sequencing study of 264 parent-child trios revealed more than 290 candidate genes in which only a single individual had a de novo variant. We sought to identify additional pathogenic variants in a subset (n = 27) of these genes via targeted sequencing in an unsolved cohort of 531 individuals with a diverse range of EEs. We report 17 individuals with pathogenic variants in seven of the 27 genes, defining a genetic etiology in 3.2% of this unsolved cohort. Our results provide definitive evidence that de novo mutations in SLC1A2 and CACNA1A cause specific EEs and expand the compendium of clinically relevant genotypes for GABRB3. We also identified EEs caused by genetic variants in ALG13, DNM1, and GNAO1 and report a mutation in IQSEC2. Notably, recurrent mutations accounted for 7/17 of the pathogenic variants identified. As a result of high-depth coverage, parental mosaicism was identified in two out of 14 cases tested with mutant allelic fractions of 5%-6% in the unaffected parents, carrying significant reproductive counseling implications. These results confirm that dysregulation in diverse cellular neuronal pathways causes EEs, and they will inform the diagnosis and management of individuals with these devastating disorders.
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