Charcot-Marie-Tooth (CMT) disease is a group of clinically and genetically heterogeneous sensorimotor peripheral neuropathies. It is the most frequent inherited neuromuscular disorder affecting 9.7-82.3 patients per 100,000 individuals. Over 100 genes with all patterns of inheritance have been linked to CMT. These genes encode proteins involved in nerve-specific processes, such as axonal transport, myelination and synaptic transmission, and in general housekeeping pathways. However, the reason underlying why defects in such ubiquitous proteins predominantly affect peripheral nerves remains unclear.
Dentatorubral-pallidoluysian atrophy (DRPLA) is a lethal neurodegenerative disorder caused by pathogenic expansion of CAG repeats within the atrophin-1 (ATN1) gene. As DRPLA belongs to the broader class of repeat expansion disorders (RED) that are driven by toxic gain-of-function effects, reduction or elimination of ATN1 expression is predicted to provide therapeutic benefit.
Neurotrimin (NTM) is a member of the IgLON family, the disruption of which has been tied to emotional learning deficits and anxiety-like behavior in animal models. A mutation in the NTM gene was found to disrupt NTM protein heterodimerization with other IgLON family members, suggesting a potential link between NTM dysfunction and neurodevelopmental and behavioral disorders.
