ArticlePLoS genetics2015
Burden analysis of rare microdeletions suggests a strong impact of neurodevelopmental genes in genetic generalised epilepsies.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Pooled it
- Computational strategies for copy number variation detection, disease association, and beyond.Genome biology · 2026Review
- Genome-wide rare copy number variations potentially associated with drug resistance in epilepsy.Scientific reports · 2026Article
- Article
- Genomic insights into autosomal recessive epilepsy: novel pathogenic variants in ITPA and CLN5 identified in consanguineous families.Molecular biology reports · 2025Article
- The Use of Synaptic Extracellular Myo-Inositol to Treat Developmental and Epileptic Encephalopathy.Annals of the Child Neurology Society · 2025Article
- Identification of a novel microdeletion at 9q21.13 in a family with epilepsy, intellectual disability, and speech disorders and literature review.Frontiers in genetics · 2025Article
- Genetic heterogeneity in familial forms of genetic generalized epilepsy: from mono- to oligogenism.Human genomics · 2024Article
- An allelic series of spontaneous Rorb mutant mice exhibit a gait phenotype, changes in retina morphology and behavior, and gene expression signatures associated with the unfolded protein response.G3 (Bethesda, Md.) · 2023Article
- Examining neurodevelopmental problems in 15q11.2 (BP1-BP2) copy number variation carriers at ages 9/12 and 18 in a Swedish twin sample.Molecular genetics & genomic medicine · 2023Article
- Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals.Nature communications · 2023Article
- Case Report-An Inherited Loss-of-FunctionGenes · 2023Article
- New Insights in 9q21.13 Microdeletion Syndrome: Genotype-Phenotype Correlation of 28 Patients.Genes · 2023Article
- Cryptic mutations of PLC family members in brain disorders: recent discoveries and a deep-learning-based approach.Brain : a journal of neurology · 2023Review
- Genetic mechanisms in generalized epilepsies.Acta epileptologica · 2023Review
- Assessment of burden and segregation profiles of CNVs in patients with epilepsy.Annals of clinical and translational neurology · 2022Article
- Article
- Rett syndrome linked to defects in forming the MeCP2/Rbfox/LASR complex in mouse models.Nature communications · 2021Article
- δ-Protocadherins regulate neural progenitor cell division by antagonizing Ryk and Wnt/β-catenin signaling.iScience · 2021Article
- Refining Genotypes and Phenotypes inInternational journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
40 authors at 18 institutions in 5 countries.
Funding
Abstract
Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes.
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