This report describes epilepsy, early-onset, 3, with or without developmental delay, a subtype of early-onset epilepsy, characterized by various types of seizures beginning in the first months or years of life. The human gene implicated is ATP6V0C, which encodes the membrane-bound subunit C of the eukaryotic multisubunit vacuolar ATPase (V-ATPase) enzyme complex. There are two high-scoring fly orthologs, Dmel\Vha16-1 and Dmel\Vha16-3, as well as several moderately scoring fly orthologs. for which classical alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\Vha16-1, and RNAi targeting constructs have been generated for Dmel\Vha16-3.
Human ATP6V0C has not been introduced into flies.
Pan-neuronally targeted RNAi knockdown of Dmel\Vha16-3 results in increased duration of seizure-like behaviour after electroshock in wandering third instar larvae. Pretreatment of larvae with established antiepileptic drugs, including levetiracetam and topiramate, resulted in significant reductions in recovery time.
[updated Sept. 2023 by FlyBase; FBrf0222196]
[EPILEPSY, EARLY-ONSET, 3, WITH OR WITHOUT DEVELOPMENTAL DELAY; EPEO3](https://omim.org/entry/620465)
[ATPase, H+ TRANSPORTING, LYSOSOMAL, 16-KD, V0 SUBUNIT C; ATP6V0C](https://omim.org/entry/108745)
Early-onset epilepsy-3 with or without developmental delay (EPEO3) is an autosomal dominant neurologic disorder characterized by the onset of various types of seizures in the first months or years of life. Many patients present with febrile seizures and later develop afebrile seizures. The severity and disease course is highly variable: some affected individuals have global developmental delay or regression with impaired intellectual development, poor or absent speech, and motor delay, whereas others have normal psychomotor development. More severely affected individuals often show additional features, including hypotonia, gait ataxia, nonspecific dysmorphic features, behavioral abnormalities, and variable anomalies on brain imaging (Mattison et al., 2023; pmid:36074901; FBrf0256332; Zhao et al., 2023; pmid:37161035). [from MIM:620465; 2023.09.08]
EPEO3 is caused by heterozygous mutation in the ATP6V0C gene on chromosome 16p13. [from MIM:620465; 2023.09.08]
The ATP6V0C gene encodes membrane-bound subunit C of the eukaryotic multisubunit vacuolar ATPase (V-ATPase) enzyme complex that functions in an ATP-dependent manner to pump protons across membranes and acidify various intracellular organelles, including lysosomes and secretory vesicles. V-ATPase also plays a role in neurotransmitter loading and release in synaptic vesicles. ATP6V0C, along with ATP6V0B, forms the intramembrane c-ring that facilitates the movement of protons across the membrane (summary by Ittiwut et al., 2021; pmid:33190975; and Mattison et al., 2023; ; pmid:36074901; FBrf0256332). [from MIM:108745; 2023.09.08]
High-scoring ortholog of human ATP6V0C (many Drosophila to 1 human).
Moderate-scoring ortholog of human ATP6V0C (many Drosophila to 1 human).
High-scoring ortholog of human ATP6V0C (many Drosophila to 1 human).
Moderate-scoring ortholog of human ATP6V0C (many Drosophila to 1 human).
Moderate-scoring ortholog of human ATP6V0C (many Drosophila to 1 human).
