Clinical, neurophysiological and genetic characteristics of Charcot-Marie-Tooth from a research center in northern China

Abstract

Background & Objectives: Charcot-Marie-Tooth (CMT) disease is a group of hereditary sensorimotor neuropathies with a great variability of genotypes and phenotypes. The aims of the study were to provide a general perspective of the clinical manifestations and the frequency of genetic subtypes in CMT patients from a medical center in Taiyuan, northern China.

Methods: Twenty-eight unrelated CMT patients were enrolled from a research center in northern China according to the CMT diagnosis criteria formulated by De Jonghe et al. in 1998. Then multiplex ligation-dependent probe amplification (MLPA) testing combined with next-generation sequencing (NGS) were performed among 18 of these patients.

Results: PMP22 duplications were identified in 8 patients. In addition, 2 novel mutations were detected in the GJB1 gene (c.236T>C and c.464T>C). According to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines, both two GJB1 mutations were assigned as ‘likely pathogenic’. PMP22 and GJB1 were the most common causative genes in CMT1 and intermediate CMT, respectively. In addition, the first CMTX6 patient with a p.R158H mutation in the PDK3 gene was confirmed in China. Our study further shows that the p.R158H of PDK3 is likely to be a recurrent mutation.

Conclusions: The results have broadened the genetic and clinical spectrums of CMT patients, which can help facilitate the diagnosis of CMT. Despite the increasing popularity of NGS, genetic screening of large cohorts of CMT patients using NGS is still rarely performed in the Chinese population. In CMT we suggest having MLPA for PMP22 as the first tier of study followed by target NGS for those with negative MLPA findings. The deciphering of the target gene candidates can further be guided by electromyographic data.