Identification and clinical characterization of Charcot-Marie-Tooth disease type 1C patients with LITAF p.G112S mutation

Background Charcot-Marie-Tooth disease type 1C (CMT1C) is a rare subtype associated with LITAF gene mutations. Until now, only a few studies have reported the clinical features of CMT1C. Objective This study was performed to find CMT1C patients with mutation of LITAF in a Korean CMT cohort and to characterize their clinical features. Methods In total, 1,143 unrelated Korean families with CMT were enrolled in a cohort. We performed whole exome sequencing to identify LITAF mutations, and examined clinical phenotypes including electrophysiological and MRI features for the identified CMT1C patients. Results We identified 10 CMT1C patients from three unrelated families with p.G112S mutation in LITAF . The frequency of CMT1C among CMT1 patients was 0.59%, which is similar to reports from Western populations. CMT1C patients showed milder symptoms than CMT1A patients. The mean CMT neuropathy score version 2 was 7.7, and the mean functional disability scale was 1.0. Electrophysiological findings showed a conduction block in 22% of affected individuals. Lower extremity MRIs showed that the superficial posterior and anterolateral compartments of the calf were predominantly affected. Conclusions We found a conduction block in Korean CMT1C patients with p.G112S mutation and first described the characteristic MRI findings of the lower extremities in patients with LITAF mutation. These findings will be helpful for genotype–phenotype correlation and will widen understanding about the clinical spectrum of CMT1C.