Neurofilament-Lysosomal Genetic Intersections in the Cortical Network of Stuttering

In this study we identified the large-scale cortical network that characterizes stuttering using functional connectivity MRI and graph theory. We performed a spatial similarity analysis that examines whether the topology of the stuttering cortical network intersects with genetic expression levels of previously reported genes for stuttering from the protein-coding transcriptome data of the Allen Human Brain Atlas. We found that GNPTG – a gene involved in the mannose-6-phosphate lysosomal targeting pathways – was significantly co-localized with the stuttering cortical network. An enrichment analysis demonstrated that the genes identified with the stuttering cortical network shared a significantly overrepresented biological functionality of Neurofilament Cytoskeleton Organization (NEFH, NEFL and INA). The relationship between lysosomal pathways, cytoskeleton organization, and stuttering, was investigated by comparing the genetic interactome between GNPTG and the neurofilament genes implicated in the current study. We found that genes of the interactome network, including CDK5, SNCA, and ACTB, act as functional links between lysosomal and neurofilament genes. These findings support stuttering is due to a lysosomal dysfunction that impart deleterious effects on the neurofilament organization of the speech neuronal circuits. They help in solving the intriguing unsolved link between lysosomal mutations and the presence of stuttering.

Source: Progress in Neurobiology - October 25, 2019 Category: Neuroscience Source Type: research