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

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Abstract

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.

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Funding

The study is financially supported by National Natural Science Foundation of China: The study of long non-coding RNA in the pathogenesis of CMT1A (81870989) and the study of mitochondrial unfolded protein response in the pathogenesis of CMT1B (81901274).

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Authors and Affiliations

  1. Neurological Department of the First Medical Center, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China

    Bo Sun, Zheng-Qing He, Yan-Ran Li, Jiong-Ming Bai, Hao-Ran Wang, Hong-Fen Wang, Fang Cui, Fei Yang & Xu-Sheng Huang

  2. Geriatric Neurological Department of the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China

    Bo Sun

  3. College of Medicine, Nankai University, Tianjin, China

    Jiong-Ming Bai & Hao-Ran Wang

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  1. Bo Sun
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  2. Zheng-Qing He
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  9. Xu-Sheng Huang
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Correspondence to Xu-Sheng Huang.

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The study was approved by the Chinese PLA General Hospital Ethics Committee. Informed written consent was obtained from all the patients enrolled in this study.

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Sun, B., He, ZQ., Li, YR. et al. Screening for SH3TC2 variants in Charcot–Marie–Tooth disease in a cohort of Chinese patients. Acta Neurol Belg 122, 1169–1175 (2022). https://doi.org/10.1007/s13760-021-01605-5

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  • DOI: https://doi.org/10.1007/s13760-021-01605-5

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