Charcot-Marie-Tooth (CMT) disease is the most common hereditary motor and sensory peripheral neuropathy, affecting approximately 1 in 2,500 individuals. Based on electrophysiological and pathological criteria, CMT is divided into the demyelinating form (CMT1) and the axonal (CMT2) form. CMT type 1 is characterized by severe reduction in motor nerve conduction velocities (NCVs) and segmental demyelination and remyelination of nerve fibers with supernumerary Schwann cells. CMT type 2 is characterized by normal to mildly reduced NCVs and axonal degeneration. Genetic studies have confirmed the heterogeneity of CMT and a number of CMT genes have been identified, including PMP22, MPZ, EGR2, LITAF, GJB1, PRX, KIF1B, RAB7, GARS, HSPB1, SBF2, MTMR2, and NEFL. A large-scale study on CMT patients revealed that mutations of NEFL accounted for about 2% of all CMT cases [Jordanova et al., 2003]. The NEFL gene encodes neurofilament light chain (NEFL or commonly known as NFL), a major component of the intermediate filament network in nerve cells. We evaluated a 71-year-old man with a chief complaint of bilateral, progressive, lower extremity weakness and easy fatigue. Neurological examination reflected no abnormality of formal mental status, cranial nerve or upper extremity motor and sensory function with the exception of mildly depressed reflexes at the brachioradialis, tricep and the bicep. There was a bilateral tendency for foot drop with a tendency to be stooped forward in a propulsive posture. The patient was unable to walk a line heel to toe. Intrinsic foot muscle atrophy was marked with pes cavus. Nerve conduction study demonstrated absent sural sensory responses. Motor responses showed a right peroneal distal latency of 6.3 m/sec (normal< 6.0) and velocity of 35 m/sec (normal> 40); comparable left peroneal responses measured 8.2 and 32 m/sec, respectively. The F wave latencies measured 57 and 75 m/sec on the right and left, respectively (normal< 54m/sec). Electromyography reflected distal more than proximal acute and chronic partial denervation with moderate loss of interference pattern in the most distal muscles and with no involvement of paraspinus muscles. His clinical diagnosis was CMT2 with distal symmetric axonal motor and sensory polyneuropathy. We sequenced a number of CMT genes of the patient, including PMP22 (CMT1A), MPZ (CMT1B and CMT2J), EGR2 (CMT1D), GJB1 (CMTX1), PRX (CMT4F), and NEFL (CMT1F and CMT2E) and tested for deletion/duplication of PMP22. A heterozygous 13 bp duplication/insertion was found in NEFL gene at position þ61 of exon 1 (c. 48_60dupGCGC-TACGTGGAG; Fig. 1A), which predicts p. T21Xfs (Fig. 1B). The wild-type NEFL (wt NEFL) protein is 543 amino acids and therefore, this mutation either markedly truncates the protein (ANEFL) or the mutation may trigger nonsense mediated decay. The proband is an adopted child and information regarding his parents, siblings and children was unavailable. We could not determine whether this is a spontaneous or an inherited mutation.