A Pro22Ser Mutation in NEFL Results in Charcot-Marie-Tooth Disease in a Chinese Family

The purpose of this study was to describe a pedigree with NEFL (c.64C>T, p. Pro22Ser, NM_006158) mutation which results in CMT (Charcot Marie Tooth) disease. This pedigree comprised 10 patients with 6 surviving cases over four generations. The clinical picture was characterized by pes cavus, distal limb weakness and atrophy and a steppage gait. Genetic testing was performed in a total of 12 subjects from this family (including 4 affected and 8 asymptomatic controls) to confirm this mutation. Electrophysiological findings revealed mixed demyelinating and axonal neuropathy. This mutation was well cosegregated with affected members in the autosomal dominant pattern. We have a pair of twins with vastly different phenotypes and genetic backgrounds in this family, giving robust evidence of genotype-phenotype correlation in CMT. A male patient was diagnosed with cancer, giving rise to the consideration of more function of this mutation.