Kari A. Mattison

The vacuolar H⁺-ATPase is an enzymatic complex that functions in an ATP-dependent manner to pump protons across membranes and acidify organelles, thereby creating the proton/pH gradient required for membrane trafficking by several different types of transporters. We describe heterozygous point variants in ATP6V0C, encoding the c-subunit in the membrane bound integral domain of the vacuolar H⁺-ATPase, in 27 patients with neurodevelopmental abnormalities with or without epilepsy. Corpus callosum hypoplasia and cardiac abnormalities were also present in some patients. In silico modelling suggested that the patient variants interfere with the interactions between the ATP6V0C and ATP6V0A subunits during ATP hydrolysis. Consistent with decreased vacuolar H⁺-ATPase activity, functional analyses conducted in Saccharomyces cerevisiae revealed reduced LysoSensor fluorescence and reduced growth in media containing varying concentrations of CaCl₂. Knockdown of ATP6V0C in Drosophila resulted in increased duration of seizure-like behaviour, and the expression of selected patient variants in Caenorhabditis elegans led to reduced growth, motor dysfunction and reduced lifespan. In summary, this study establishes ATP6V0C as an important disease gene, describes the clinical features of the associated neurodevelopmental disorder and provides insight into disease mechanisms.

Young researchers are often excluded from the scholarly processes of peer‐review and publication, which are cornerstones of scholarly work. The Journal of Emerging Investigators is an open access journal dedicated to publishing the research of middle and high school students. We surveyed student authors before and after they participated in the peer‐review and publication process of their scientific articles. Following peer‐review and publication, students report gains in their confidence and self‐efficacy in science, and increased feelings of identity and belonging in science. Our findings demonstrate that even the youngest scholars are capable of participating in the publication process, and our data suggest that participation in the process has positive outcomes.