ArticleAnnals of neurology2018
Somatic SLC35A2 variants in the brain are associated with intractable neocortical epilepsy.
Article in Annals of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 134 citations in OpenAlex.
- Somatic mosaicism in the brain: linking development, ageing and neurodegeneration.Nature reviews. Neurology · 2026Review
- Article
- Deep tissue sequencing improves genetic diagnostic yield in focal cortical dysplasia.Progress in neuro-psychopharmacology & biological psychiatry · 2026Article
- Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE): genetics, mechanisms and precision therapy.Acta neuropathologica · 2026Review
- Somatic variants activating the RAS-MAPK pathway confer susceptibility to hippocampal sclerosis in drug-resistant epilepsy.bioRxiv : the preprint server for biology · 2026Article
- Disrupted O-GalNAc glycosylation as a mechanism and biomarker ofbioRxiv : the preprint server for biology · 2026Article
- 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
- Olig2-specific loss-of-function Slc35a2 results in hypomyelination and spontaneous seizures.Epilepsia · 2026Article
- Activating Ras-MAPK pathway variants drive hippocampal clonal competition in human epilepsy.bioRxiv : the preprint server for biology · 2026Article
- Focal cortical dysplasias: modeling pediatric drug-resistant epilepsy using human brain organoids.Frontiers in cellular neuroscience · 2026Review
- Early death and neuronal abnormalities inbioRxiv : the preprint server for biology · 2025Article
- SLC35A2 loss-of-function variants affect glycomic signatures, neuronal fate and network dynamics.Brain : a journal of neurology · 2025Article
- Review
- Glycosphingolipid synthesis is impaired in SLC35A2-CDG and improves with galactose supplementation.Cellular and molecular life sciences : CMLS · 2025Article
- Somatic variants in SLC35A2 leading to defects in N-glycosylation in mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE).Acta neuropathologica · 2025Article
- Somatic Mosaicism in Brain Disorders.Annual review of pathology · 2025Review
- Developmental and Epileptic Encephalopathies: Need for Bridging the Gaps Between Clinical Syndromes and Underlying Genetic Etiologies.Indian journal of pediatrics · 2025Review
- Genetic variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfate diversity.Essays in biochemistry · 2024Review
- Article
- Loss of Slc35a2 alters development of the mouse cerebral cortex.Neuroscience letters · 2024Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
34 authors at 11 institutions in 1 country.
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Abstract
objectiveSomatic variants are a recognized cause of epilepsy-associated focal malformations of cortical development (MCD). We hypothesized that somatic variants may underlie a wider range of focal epilepsy, including nonlesional focal epilepsy (NLFE). Through genetic analysis of brain tissue, we evaluated the role of somatic variation in focal epilepsy with and without MCD.
methodsWe identified somatic variants through high-depth exome and ultra-high-depth candidate gene sequencing of DNA from epilepsy surgery specimens and leukocytes from 18 individuals with NLFE and 38 with focal MCD.
resultsWe observed somatic variants in 5 cases in SLC35A2, a gene associated with glycosylation defects and rare X-linked epileptic encephalopathies. Nonsynonymous variants in SLC35A2 were detected in resected brain, and absent from leukocytes, in 3 of 18 individuals (17%) with NLFE, 1 female and 2 males, with variant allele frequencies (VAFs) in brain-derived DNA of 2 to 14%. Pathologic evaluation revealed focal cortical dysplasia type Ia (FCD1a) in 2 of the 3 NLFE cases. In the MCD cohort, nonsynonymous variants in SCL35A2 were detected in the brains of 2 males with intractable epilepsy, developmental delay, and magnetic resonance imaging suggesting FCD, with VAFs of 19 to 53%; Evidence for FCD was not observed in either brain tissue specimen.
interpretationWe report somatic variants in SLC35A2 as an explanation for a substantial fraction of NLFE, a largely unexplained condition, as well as focal MCD, previously shown to result from somatic mutation but until now only in PI3K-AKT-mTOR pathway genes. Collectively, our findings suggest a larger role than previously recognized for glycosylation defects in the intractable epilepsies. Ann Neurol 2018.
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