Screening for SH3TC2 variants in Charcot–Marie–Tooth disease in a cohort of Chinese patients

• Published in: Acta neurologica Belgica 2022-10, Vol.122 (5), p.1169-1175
• Main Authors: Sun, Bo, He, Zheng-Qing, Li, Yan-Ran, Bai, Jiong-Ming, Wang, Hao-Ran, Wang, Hong-Fen, Cui, Fang, Yang, Fei, Huang, Xu-Sheng
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Medicine/Public Health; Neurology; Neuroradiology; Neurosciences; Original Article
• ISSN: 0300-9009; 2240-2993
• DOI: 10.1007/s13760-021-01605-5

Mutations in the SH3TC2 gene cause Charcot–Marie–Tooth disease type 4C (CMT4C), characterized by inherited demyelinating peripheral neuropathy. CMT4C is a common form of CMT4/autosomal recessive (AR) CMT1. This study examined the SH3TC2 variants, investigated genotype–phenotype correlations and explored the frequency of CMT4C in Chinese patients. A total of 206 unrelated patients of Chinese Han descent clinically diagnosed with CMT were recruited. All patients underwent detailed history-taking, neurological examination, laboratory workups, and electrophysiological studies. Genetic analysis was performed via high-throughput target sequencing (NGS). Three patients, one male and two females, were found to carry five SH3TC2 mutations: patient 1 (c.3154C > T, p.R1054X; c.929G > A, p.G310E); Patient 2 (c.2872_2872del, p.S958fs; c.3710C > T, p.A1237V) and Patient 3 (c.2782C > T, p.Q928X; c.929G > A, p.G310E). The c.2872_2872del, c.3710C > T and c.2782C > T variants were not reported before. CMT4C caused by SH3TC2 mutation is a very common type of CMT4/AR CMT1. Three novel mutations, c.2872_2872del, c.3710C > T and c.2782C > T, were found in this study. Combination of clinical phenotype, nerve conduction studies, genetic analysis and bioinformatics analysis are of vital importance in patients suspected as CMT.