ArticleEuropean journal of human genetics : EJHG2019
The role of recessive inheritance in early-onset epileptic encephalopathies: a combined whole-exome sequencing and copy number study.
Article in European journal of human genetics : EJHG, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- AFG2A-related encephalopathy, expanding the neurodevelopmental and epileptic spectrum.Orphanet journal of rare diseases · 2026Pooled it
- Decoding the mechanisms of cooperative DNA binding by the Paired-like homeodomain family.Nature communications · 2026Article
- Case report: Characterization of a patient with novel biallelic variants inFrontiers in genetics · 2026Article
- Decoding the mechanisms of cooperative DNA binding by the Paired-like homeodomain family.bioRxiv : the preprint server for biology · 2025Article
- Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies.Biomolecules · 2025Review
- Developmental and Epileptic Encephalopathies: Need for Bridging the Gaps Between Clinical Syndromes and Underlying Genetic Etiologies.Indian journal of pediatrics · 2025Review
- Biallelic variants in GTF3C3 result in an autosomal recessive disorder with intellectual disability.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- Biallelic variants inBrain communications · 2025Article
- National survey on the prevalence of single-gene aetiologies for genetic developmental and epileptic encephalopathies in Italy.Journal of medical genetics · 2024Article
- Customized targeted massively parallel sequencing enables the identification of novel pathogenic variants in Tunisian patients with developmental and epileptic encephalopathy.Epilepsia open · 2024Article
- A novel compound heterozygous mutation of UFC1 in a patient with neurodevelopmental disorder.Genes & genomics · 2024Article
- Missense variants in ANO4 cause sporadic encephalopathic or familial epilepsy with evidence for a dominant-negative effect.American journal of human genetics · 2024Article
- Biallelic variants in GTF3C5, a regulator of RNA polymerase III-mediated transcription, cause a multisystem developmental disorder.Human genetics · 2024Article
- Adult-Onset Transcriptomic Effects of Developmental Exposure to Benzene in Zebrafish (International journal of molecular sciences · 2023Article
- Steps to Improve Precision Medicine in Epilepsy.Molecular diagnosis & therapy · 2023Article
- Natural History and Developmental Trajectories of Individuals With Disease-Causing Variants inNeurology · 2023Article
- The current benefit of genome sequencing compared to exome sequencing in patients with developmental or epileptic encephalopathies.Molecular genetics & genomic medicine · 2023Article
- Neuroimaging in PRUNE1 syndrome: a mini-review of the literature.Frontiers in neurology · 2023Review
- Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum.Physiological reviews · 2023Review
- Whole-exome sequencing of a Saudi epilepsy cohort reveals association signals in known and potentially novel loci.Human genomics · 2022Article
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Authors and funding
31 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Early-onset epileptic encephalopathy (EE) and combined developmental and epileptic encephalopathies (DEE) are clinically and genetically heterogeneous severely devastating conditions. Recent studies emphasized de novo variants as major underlying cause suggesting a generally low-recurrence risk. In order to better understand the full genetic landscape of EE and DEE, we performed high-resolution chromosomal microarray analysis in combination with whole-exome sequencing in 63 deeply phenotyped independent patients. After bioinformatic filtering for rare variants, diagnostic yield was improved for recessive disorders by manual data curation as well as molecular modeling of missense variants and untargeted plasma-metabolomics in selected patients. In total, we yielded a diagnosis in ∼42% of cases with causative copy number variants in 6 patients (∼10%) and causative sequence variants in 16 established disease genes in 20 patients (∼32%), including compound heterozygosity for causative sequence and copy number variants in one patient. In total, 38% of diagnosed cases were caused by recessive genes, of which two cases escaped automatic calling due to one allele occurring de novo. Notably, we found the recessive gene SPATA5 causative in as much as 3% of our cohort, indicating that it may have been underdiagnosed in previous studies. We further support candidacy for neurodevelopmental disorders of four previously described genes (PIK3AP1, GTF3C3, UFC1, and WRAP53), three of which also followed a recessive inheritance pattern. Our results therefore confirm the importance of de novo causative gene variants in EE/DEE, but additionally illustrate the major role of mostly compound heterozygous or hemizygous recessive inheritance and consequently high-recurrence risk.
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