Charcot-Marie-Tooth Disease in Chinese Family



CMT is an umbrella term which refers to a homogeneous group of clinical phenotypes, including progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss and usually decreased tendon reflexes. CMT is genetically heterogeneous, caused by more than 1000 mutations in 80 disease-associated genes [1]. It is originally divided into two major subgroups, CMT1 and CMT2, according to electrophysiological appraisal and tissue biopsy, along with the molecular diagnostic, and each subgroup is further divided into several subtypes by genetic locus. CMT1 is a demyelinating peripheral neuropathy where myelinating Schwann cells are affected and median nerve motor nerve conduction velocity (MNCV) is below 38 m/s [2]. CMT2 is characterized by axonopathy with MNCVs normal (>40-45 m/s) or slightly reduced (30–40 m/s) [3]. Another term of intermediate CMT was coined to cover an overlapping situation between CMT1 and CMT2, with both myelin and axonal phenotypes and MNCVs between 25 and 45 m/s [2,4]. The mutations of NEFL gene cause either CMT2E or CMT1F phenotype, comprising about 0.8% to 2% in all CMT patients according to different research [5-7]. NEFL encodes neurofilament light-chain polypeptide, belonging to one of the neurofilament triplet subunits, which are NEFL (Neurofilament light chain), NEFM (Neurofilament middle chain) and NEFH (Neurofilament heavy chain) respectively [8,9]. Neurofilaments (NFs) are neuron-specific and crosslink with each other to form a highly stable cytoskeleton in large myelinated axons [10,11]. The widely extended network is responsible for maintaining the axonal diameter and transport [11,12]. Pro22Ser mutation of NEFL could cause CMT2E, which was first reported in a large Slovenian family by Georgiou in 2002 [13]. A case in a Japanese family showed that the symptom of CMT2E could be resulted from Pro22Thr mutation [14]. Another study by Shin reported Pro22Arg lead to CMT1F phenotype [15]. Here we reported a Chinese family, and ten of the family members were troubled by distal limb weakness and had difficulty in running as their normal counterparts in their second to third decades. CMT was diagnosed by electrophysiological examinations and typical clinical manifestations. Genetic analysis revealed that the mutation of NEFL, p. Pro22Ser, (c.64C>T, NM_006158) might be responsible for the disease

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International Journal of Case Reports