A Chinese kindred report of Charcot-Marie-Tooth Disease Type 4C with the novel compound heterozygous variants in the SH3TC2 gene and a systematic review

Abstract Charcot-Marie-Tooth disease type 4C (CMT4C) is an autosomal recessive neuropathy caused by SH3TC2 mutations, characterized clinically by early-onset severe scoliosis, foot deformities, predominantly distal weakness, muscle atrophy, sensory loss and cranial nerve deficits. Most patients carry missense mutations and nonsense mutations in chromosome 5q23-33 of SH3TC2 gene associated with Schwann cells. Through linkage, haplotype and sequencing analysis in a kindred from northern China with three members affected by autosomal recessive peripheral neuropathy, we identified the compound heterozygous mutations Q244X and L1048P in SH3TC2. Onset age ranged from 6 to 43 years and all three of them had hearing loss as their first symptom. Neuropathy was moderate-to-severe. Scoliosis, foot deformities, predominantly distal weakness, muscle atrophy, sensory loss and cranial nerve deficits were present in all of them. Our study of this family expands the spectrum of mutations causing CMT4C with the discovery of a novel nonsense mutation in the SH3TC2 gene. Further more, due to the weak correlation between the nature and the position of the pathogenic variant, disease duration, and the stage of disability of CMT4C, we conducted a systematic review and evaluation of the previous literatures to further analyze the clinical findings of CMT4C.