Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The cause of epilepsy with or without developmental disorders was unidentified in a significant proportion of patients. Whole exome sequencing was performed in three unrelated patients with early-onset epilepsy, with or without developmental delay and intellectual disability. We identified de novo heterozygous variants (p.Arg119Trp, p.Val99_Ser102del, c.260_263 + 11delinsGCCCA) in the ATP6V0C gene, which encodes a subunit of vacuolar ATPase. Three-dimensional protein modeling showed that the variant p.Arg119Trp in ATP6V0C affected the hydrogen bonds with the 115 and 123 residues, and the protein stability. The p.Val99_Ser102del and c.260_263 + 11delinsGCCCA variants in the other two patients resulted in a loss of function with microdeletion or splicing effects. Their seizures and psychomotor developmental outcomes were different, and all patients had a good prognosis. Our study provides evidence that de novo heterozygous ATP6V0C variants are related to epilepsy and associated with or without developmental delay.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s10038-023-01145-1 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mixed functional consequences of the N651D variant: a case of early-onset developmental and epileptic encephalopathy with parkinsonism.
J Med Genet
September 2025
Department of Pediatrics, Danish Epilepsy Center, Dianalund, Denmark
Rare variants in , the gene encoding the GluA3 subunit of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs), are associated with defects in early brain development. Disease-causing variants are generally categorised as either loss of function (LoF) or gain of function (GoF) that appear to be linked to different symptoms. Here, we reported a de novo variant (N651D) that has mixed LoF and GoF in a female patient with a devastating developmental and epileptic encephalopathy, parkinsonism and cortical malformation.
View Article and Find Full Text PDFRegulation of neurogenesis and neuronal migration by Rrm2 and Timp3 following seizures.
Neurobiol Dis
September 2025
Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, TX, USA; Brain Health Consortium, The University of Texas at San Antonio, San Antonio, TX, USA. Electronic address:
Temporal lobe epilepsy is associated with aberrant neurogenesis and ectopic migration of adult-born granule cells (abGCs), yet the molecular mechanisms driving these changes remain poorly defined. Using a pilocarpine-induced mouse model of temporal lobe epilepsy and chemogenetic silencing of abGCs via Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we previously demonstrated that abGC inhibition reduces both ectopic migration and seizure susceptibility. To identify underlying molecular regulators, we performed RNA sequencing of FACS-isolated abGCs and identified Rrm2 and Timp3 as top candidate genes modulated by seizure activity and neuronal silencing.
View Article and Find Full Text PDFExcitatory cortical neurons from CDKL5 deficiency disorder patient-derived organoids show early hyperexcitability not identified in neurogenin2 induced neurons.
Neurobiol Dis
September 2025
F.M. Kirby Neurobiology Department, Boston Children's Hospital, Boston, MA, USA; Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Human Neuron Core, Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Boston, MA, USA.
CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy resulting from variants in cyclin-dependent kinase-like 5 (CDKL5) that lead to impaired kinase activity or loss of function. CDD is one of the most common genetic etiologies identified in epilepsy cohorts. To study how CDKL5 variants impact human neuronal activity, gene expression and morphology, CDD patient-derived induced pluripotent stem cells and their isogenic controls were differentiated into excitatory neurons using either an NGN2 induction protocol or a guided cortical organoid differentiation.
View Article and Find Full Text PDFA clinical and genotype-phenotype analysis of MACF1 variants.
Am J Hum Genet
September 2025
Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, Rotterdam 3000 CA, the Netherlands.
Microtubule-actin cross-linking factor 1 (MACF1) is a large protein of the spectraplakin family, which is essential for brain development. MACF1 interacts with microtubules through the growth arrest-specific 2 (Gas2)-related (GAR) domain. Heterozygous MACF1 missense variants affecting the zinc-binding residues in this domain result in a distinctive cortical and brain stem malformation.
View Article and Find Full Text PDFCortical versus hippocampal network dysfunction in a human brain assembloid model of epilepsy and intellectual disability.
Cell Rep
September 2025
Department of Neurology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA; Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Un
Neurodevelopmental disorders often impair multiple cognitive domains. For instance, a genetic epilepsy syndrome might cause seizures due to cortical hyperexcitability and present with memory impairments arising from hippocampal dysfunction. This study examines how a single disorder differentially affects distinct brain regions using induced pluripotent stem cell (iPSC)-derived cortical- and hippocampal-ganglionic eminence assembloids to model developmental and epileptic encephalopathy 13, a condition arising from gain-of-function mutations in the SCN8A gene encoding the sodium channel Nav1.
View Article and Find Full Text PDF