Absence of NEFL in patient-specific neurons in early-onset Charcot-Marie-Tooth neuropathy

OBJECTIVE: ) underlying early-onset Charcot-Marie-Tooth (CMT) disease. METHODS: . Quantitative PCR, protein analytics, immunocytochemistry, electron microscopy, and single-cell transcriptomics were used to investigate patient and control neurons. RESULTS: mRNA. CONCLUSIONS: nonsense mutations. Here, we show that such mutation leads to the absence of NEFL, causing childhood-onset neuropathy through a loss-of-function mechanism. We propose that the neurofilament accumulation, a common feature of many neurodegenerative diseases, mimics the absence of NEFL seen in recessive CMT if aggregation prevents the proper localization of wild-type NEFL in neurons. Our results suggest that the removal of NEFL as a proposed treatment option is harmful in humans.