Single nucleotide variants in <i>UNC13C</i> associated with neurodevelopmental disorders affect ethanol sensitivity in <i>Drosophila</i>.

ABSTRACT: UNC13s are presynaptic proteins essential for neurotransmitter release at chemical synapses. In this study, we present eleven patients from nine families with severe neurodevelopmental impairments, who carry rare, biallelic UNC13C single-nucleotide variants (SNVs). Six missense variants, each identified in compound heterozygosity in one of three of these patients, were introduced into the Drosophila melanogaster ortholog unc13 using a previously established CRISPR/Cas9-based method for rapid and scarless genomic modifications, hypothesising that they underlie the observed clinical manifestations. However, none of the introduced mutations influenced Mendelian ratios, negative geotaxis, or lifespan of the fruit flies. Interestingly, two variants located outside the gene

SUBMITTER: Muller F 

PROVIDER: S-EPMC12702192 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature