Clinical and electrophysiological features in Charcot-Marie-Tooth disease with mutations in the NEFL gene

Background: To date, 13 different neurofilament light-chain polypeptide gene ( NEFL) mutations have been identified in 55 patients with Charcot-Marie-Tooth disease( CMT) from 16 families. NEFL mutations were found to be associated with axonal and demyelinating variants of CMT. Objectives: To describe the clinical features of 11 patients with CMT and NEFL mutations and to explore possible genotype-phenotype correlations. Design: Standardized neuromuscular and nerve conduction studies were performed, and the coding regions of the peripheral myelin protein 22 ( PMP22), myelin protein zero ( MPZ), gap junction beta-1 protein ( GJB1), and NEFL genes were analyzed by direct DNA sequencing. Setting: Two university hospitals in Austria ( referral centers for neuromuscular disorders). Patients: Eleven patients with CMT and NEFL mutations. Main Outcome Measure: We genotyped NEFL in all of the patients and healthy relatives and correlated the genotype with the phenotype. Results: A novel NEFL mutation ( p.L93P) was detected in 1 family with 4 affected individuals exhibiting a severe CMT phenotype. Nerve conduction velocities were intermediately slowed to a range of 35 to 39 m/s. In a second family and in a sporadic patient, a p.P8R mutation was identified with intermediate and severe nerve conduction slowing. Conclusion: The results argue against an obvious genotype-phenotype correlation regarding disease onset, degree of muscle weakness, and nerve conduction slowing caused by NEFL mutations.